At the end of every month, the International Myeloma Foundation Newsroom will feature a wrap-up of some of the most fascinating studies about multiple myeloma from medical journals. Here is the March 2026 edition.
The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.
In the Journals (Key Myeloma Research in March 2026)
"The clinically available supplement pyruvate enhances the therapeutic effect of bortezomib in Multiple Myeloma by modulating mitochondrial metabolism"
Source
Chenggong Tu, Arne Van der Vreken, Sylvia Faict, Gamze Ates, Ann Massie, Kim De Veirman, Elke De Bruyne, Karin Vanderkerken, Eline Menu, The clinically available supplement pyruvate enhances the therapeutic effect of bortezomib in Multiple Myeloma by modulating mitochondrial metabolism, Cancer Letters, Volume 640, 2026, 218245, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2026.218245. March 1, 2026.
Overview
Despite advances in treatment, many people with multiple myeloma eventually develop resistance to drugs like the proteasome inhibitor bortezomib. This study explored how myeloma cells use energy, focusing on mitochondria, the parts of the cell that produce energy and control levels of reactive oxygen species (ROS), which can damage and kill cancer cells. The researchers found that pyruvate, a key molecule in energy metabolism, boosts mitochondrial activity and increases ROS levels, while also activating a cellular stress pathway known as the integrated stress response.
By contrast, metformin, a drug that blocks part of the cell’s energy production process, lowered ROS levels and reduced the cancer-killing effects of bortezomib, even though it still triggered the same stress response. These findings were seen in both lab models and patient samples. In addition, an analysis of patient data showed that individuals who had longer periods without disease progression on proteasome inhibitors tended to have higher activity in mitochondrial energy pathways.
These results suggest that mitochondrial metabolism plays an important role in how myeloma responds to treatment. Targeting pyruvate metabolism to increase ROS levels may help improve the effectiveness of bortezomib and offers a potential new strategy to overcome drug resistance.
"Discovery and Characterization of VPRBP/DCAF1 Kinase Inhibitor Analogs as Microtubular Destabilizing Agents with Potent Anti-myeloma Activity"
Source
Olivia Susanto, Emily Gruber, Cheng Mun Wun, Rheana L. Franich, Xiao Ma, Zahra Sabouri-Thompson, Zoe J. Porter, Heather C. Murray, Leonie A. Cluse, Belinda Maher, Daniella Brasacchio, Benjamin P. Martin, Peter J. Fraser, Iva Nikolic, Gisela Mir Arnau, Jarrod J. Sandow, Kaylene J. Simpson, Nicole M. Verrills, Ricky W. Johnstone, Philip E. Thompson, Lev M. Kats, Jake Shortt; Discovery and Characterization of VPRBP/DCAF1 Kinase Inhibitor Analogs as Microtubular Destabilizing Agents with Potent Antimyeloma Activity. Mol Cancer Ther 1 March 2026; 25 (3): 416–434. https://doi.org/10.1158/1535-7163.MCT-25-0306
Overview
Treatments like thalidomide-based drugs and proteasome inhibitors work in multiple myeloma by disrupting how cells manage and break down proteins. In this study, researchers looked for other weak points in this system that could be targeted. They focused on a group of proteins called DCAF factors and found that one of them, DCAF1, is essential for myeloma cell survival and may be a promising new drug target.
The team then developed new versions of a drug designed to block DCAF1, making them more effective against myeloma cells. However, they discovered that these drugs were not working in the way they originally expected. Instead of acting mainly through DCAF1’s known function, the drugs appeared to disrupt microtubules, which are important structures that help cells divide and survive.
Further testing showed that these drug candidates could kill myeloma cells in the lab and had activity in animal models of myeloma and lymphoma. Overall, the findings suggest that targeting DCAF1-related pathways, including effects on microtubules, could lead to new treatment options, especially for patients whose disease no longer responds to current therapies.
"CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models"
Source
Paul Lin, Sunil Acharya, Francia Reyes-Silva, Rafet Basar, Nadima Uprety, Luz Yurany Moreno Rueda, Pei Lin, April L. Gilbert, Pinaki P. Banerjee, Dexing Fang, Chenyu Zhang, Ana Karen Nunez Cortes, Luciana Melo Garcia, May Daher, Luis Muniz-Feliciano, Gary M. Deyter, Vernikka Woods, Seema Rawal, Ping Li, Corry M. Jones, Rejeena Shrestha, Muzaffar H. Qazilbash, Krina K. Patel, Hans C. Lee, Richard E. Champlin, David Marin, Elizabeth J. Shpall, Robert Z. Orlowski, Katayoun Rezvani; CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models. Blood Cancer Discov 1 March 2026; 7 (2): 234–249. https://doi.org/10.1158/2643-3230.BCD-25-0130
Overview
This study looked at CD70, a protein found on the surface of many cancer cells, including multiple myeloma cells. Researchers found that CD70 levels are higher in patients with high-risk disease and are linked to worse survival outcomes. These findings were confirmed using several advanced lab techniques and across different patient groups, suggesting that CD70 could be an important marker of more aggressive myeloma.
The researchers then tested a new treatment approach using natural killer (NK) cells that were engineered with a chimeric antigen receptor (CAR) to target CD70. These modified cells, called CAR27/IL-15 NK cells, were designed to better recognize and attack myeloma cells. In both lab studies and animal models, these cells were highly effective at killing CD70-positive myeloma cells, with results similar to CAR T-cell therapies. Importantly, they also worked in models where BCMA, a common treatment target, was no longer present.
This study suggests that CD70 is a promising new target, especially for patients with high-risk disease or those who have relapsed after BCMA-directed therapies. These early findings support ongoing clinical trials testing CD70-targeted CAR NK cell therapy in people with multiple myeloma.
"First-line Therapy in Newly Diagnosed Multiple Myeloma"
Source
Kevin C. Miller, Saad Z. Usmani; First-line Therapy in Newly Diagnosed Multiple Myeloma. Blood Cancer Discov 1 March 2026; 7 (2): 195–211. https://doi.org/10.1158/2643-3230.BCD-25-0384
Overview
Treatment for newly diagnosed multiple myeloma has improved significantly over time, moving from older two-drug combinations to more advanced four-drug regimens that include proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and stem cell transplant. These approaches have helped patients live longer, but treatment is still often given continuously and in a similar way for most people.
This review explains how doctors are starting to better tailor treatment based on a patient’s individual disease risk and response to therapy. One important tool is measuring minimal or measurable residual disease (MRD), which looks for very small amounts of cancer left after treatment. Using MRD results to guide decisions may help doctors adjust therapy more precisely.
The review also highlights newer immunotherapy approaches, such as CAR T-cell therapy and bispecific antibodies, which are now being studied earlier in treatment. These advances raise the possibility that some patients may achieve long-lasting remissions without needing ongoing therapy. Overall, the goal is to move toward more personalized treatment plans that balance effectiveness, side effects, and quality of life, with the hope of achieving functional cures for some patients.
"Longitudinal Profiling of Tumor and Immune Compartments Uncovers Patterns of Dysregulation and Associations with Response in Multiple Myeloma"
Source
Denis J. Ohlstrom, William C. Pilcher, Marina E. Michaud, Chaitanya Acharya, Sarthak Satpathy, Edgar Gonzalez-Kozlova, Reyka G. Jayasinghe, Katherine Ferguson, Hope L. Mumme, Shivani Nanda, Yizhe Song, Sowmitri Mantrala, Dimitra Karagkouni, Jessica Schulman, Nick Pabustan, Junia Vieira Dos Santos, Daniel W. Sherbenou, Jonathan J. Keats, Alexander M. Gout, Steven Foltz, Alessandro Lagana, Taxiarchis Kourelis, Ravi Vij, Madhav V. Dhodapkar, David Avigan, Hearn Jay Cho, Linda B. Baughn, Ajay K. Nooka, Sagar Lonial, Shaji Kumar, Mehmet K. Samur, Ioannis S. Vlachos, Li Ding, Sacha Gnjatic, George Mulligan, Manoj K. Bhasin; Longitudinal Profiling of Tumor and Immune Compartments Uncovers Patterns of Dysregulation and Associations with Response in Multiple Myeloma. Blood Cancer Discov 1 March 2026; 7 (2): 266–286. https://doi.org/10.1158/2643-3230.BCD-25-0205
Overview
This study looked at how the immune system interacts with myeloma cells over time, especially during treatment and at relapse. Researchers analyzed bone marrow samples from patients at different stages of disease using advanced genetic and single-cell techniques. They found that certain immune signals, such as interferon-gamma activity, were linked to weaker long-term T-cell memory after stem cell transplant, which may affect how well the immune system can keep the disease under control.
On the other hand, patients who had higher levels of naïve B cells and a more diverse range of antibodies tended to have longer periods without disease progression. This suggests that recovery of healthy B cells after treatment may be an important sign of a stronger and more durable response.
At the time of disease progression, the immune environment changed in ways that may help the cancer grow. Myeloma cells increased expression of certain proteins called cancer-testis antigens, while immune cells showed signs of exhaustion and reduced activity. There was also a decrease in B cells and an increase in immune-suppressing cells.
This study shows that the interaction between myeloma and the immune system is constantly changing. Monitoring these immune changes could help predict how patients respond to treatment and identify new targets, such as cancer-testis antigens, for future therapies.
"Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment"
Source
Anjana Anilkumar Sithara, Veronika Kapustova, David Zihala, Ondrej Venglar, Daniel Bilek, Moutaz Helal, Mara John, Eva Radova, Lucie Broskevicova, Jan Vrana, Gabriela Havlova, Ludmila Muronova, Tereza Popkova, Jana Mihalyova, Hana Plonkova, Serafim Nenarokov, Kamlesh Bisht, Hongfang Wang, Helgi Van de Velde, Sandra Charvatova, Ivo Demel, Michal Kascak, Milan Navratil, Martin Havel, Juli Bago, Michal Simicek, Angela Riedel, Leo Rasche, Tereza Sevcikova, Ola Landgren, Roman Hajek, Tomas Jelinek; Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment. Blood Cancer Discov 1 March 2026; 7 (2): 250–265. https://doi.org/10.1158/2643-3230.BCD-25-0170
Overview
Extramedullary multiple myeloma (EMM) is a more aggressive form of the disease that occurs outside the bone marrow and is often harder to treat, even with newer therapies. In this study, researchers examined the immune environment within EMM tumors and compared it to the bone marrow using advanced techniques that analyze individual cells and their location.
They found that while T cells and natural killer (NK) cells were the most common immune cells in EMM tumors, their ability to fight cancer appeared weaker than in the bone marrow. EMM tumors had fewer CD4+ T cells, a lower ratio of active immune cells to cancer cells, and a higher number of a less active type of NK cell. In about half of the cases, CD8+ T cells, which normally kill cancer cells, showed signs of exhaustion, meaning they were less effective.
The researchers also found higher levels of “immune checkpoint” signals, such as PD-1 and NKG2A, which can turn off immune responses and allow cancer cells to escape attack. Overall, these findings suggest that the immune environment in EMM is more suppressive and less effective at controlling the disease, which may help explain why EMM is more resistant to treatment and point to new targets for therapy.
"Rethinking Multiple Myeloma Treatment: The Biological and Clinical Insights Guiding Immune-Based Combinations"
Source
Annamaria Gullà, Madhav V. Dhodapkar, Hermann Einsele, Marc S. Raab, Antonio G. Solimando, Cirino Botta, Marcello Turi, Lilli S. Sester, Andrew J. Portuguese, Torsten Steinbrunn, Kenneth C. Anderson; Rethinking Multiple Myeloma Treatment: The Biological and Clinical Insights Guiding Immune-Based Combinations. Blood Cancer Discov 1 March 2026; 7 (2): 176–194. https://doi.org/10.1158/2643-3230.BCD-25-0107
Overview
Immune-based treatments, such as immunotherapies, have become an important part of care for multiple myeloma. However, it is still challenging to achieve long-lasting control of the disease, especially for patients with high-risk features. This review looks at how current and emerging treatments affect the immune system and why some patients develop resistance over time.
The authors explain that both the cancer cells and the immune system can adapt in ways that reduce treatment effectiveness. To address this, researchers are studying better ways to combine therapies and decide the right order to use them, with the goal of improving and extending treatment responses. Ongoing clinical trials are testing these strategies to find the most effective approaches.
Overall, this research suggests that future treatment may focus more on strengthening the body’s natural immune response while also using engineered immune therapies. The goal is to move beyond simply controlling the disease and instead achieve deep, lasting responses by eliminating remaining cancer cells and creating long-term immune protection tailored to each patient.
"GELAMM, Diagnosis and management of multiple myeloma bone disease in Latin America: a GELAMM regional survey"
Source
Carolina Romero, Natalia Schutz, Eloisa Riva, Camila Peña; on behalf of GELAMM, Diagnosis and management of multiple myeloma bone disease in Latin America: a GELAMM regional survey. Blood Global Hematology 2026; 2 (1): 100037. doi: https://doi.org/10.1016/j.bglo.2025.100037 March 1, 2026.
Overview
Myeloma-related bone disease is very common and can lead to serious problems like fractures, spinal cord compression, and high calcium levels, all of which can reduce quality of life and increase healthcare costs. This study surveyed over 200 doctors across Latin America to understand how bone disease in multiple myeloma is diagnosed and treated in real-world settings. The results showed wide differences in care, especially between public and private healthcare systems.
Although international guidelines recommend advanced imaging like PET-CT, whole-body CT, or MRI to detect bone damage early, many doctors still rely on standard X-rays, which can miss disease until it is more advanced. Limited access to newer imaging tools, particularly in public healthcare systems, appears to be a major reason for this gap. Early and accurate detection is important because it can help prevent fractures and other serious complications.
Most doctors reported using bone-strengthening treatments, such as zoledronic acid, but not always in line with guidelines. While many prescribe these drugs to all patients at diagnosis, others only use them when bone damage is already visible. Access to another option, denosumab, was more limited, especially in public settings. In patients with poor kidney function, where denosumab may be safer, many doctors reported not using any bone-protective treatment, suggesting an area for improvement.
The survey also found variation in how long and how often these treatments are given, as well as in supportive care practices like dental exams and vitamin D supplementation. Some patients may experience delays in starting treatment بسبب required dental checks, and not all patients receive recommended supplements to support bone health.
Overall, the findings highlight important gaps between guideline recommendations and actual practice in Latin America. Differences in access to imaging, medications, and supportive care contribute to unequal treatment. Improving access to early diagnosis and standardizing care could help reduce fractures, improve quality of life, and lower healthcare costs for patients with multiple myeloma.
"Research on predicting the progression of multiple myeloma treated with bortezomib based on multimodal ensemble learning"
Source
Li S, Zang B, Jia J, Zhao Y, Zong H, Huo H, Geng C. Research on predicting the progression of multiple myeloma treated with bortezomib based on multimodal ensemble learning. Digit Health. 2026 Mar 2;12:20552076261430213. doi: 10.1177/20552076261430213.
Overview
This study looked at whether artificial intelligence (AI) could help predict how multiple myeloma will progress in patients receiving bortezomib. Because patients respond differently to treatment, being able to identify high-risk patients early could help doctors choose the most effective treatment plan and avoid unnecessary side effects.
Researchers analyzed data from over 200 newly diagnosed patients, including bone marrow images, protein electrophoresis images, and basic clinical information. They used several AI models to study each type of data and then combined them into a single “multimodal” model. This combined approach performed better than any single type of data alone in predicting which patients were more likely to see their disease progress within two years.
Among the individual data types, protein electrophoresis images provided the most useful information, while bone marrow images and clinical data also contributed to the overall prediction. By combining all of these inputs, the model achieved stronger and more accurate results.
Overall, this study suggests that AI tools that integrate multiple types of patient data may help doctors better predict disease progression and personalize treatment. In the future, this kind of approach could support more informed decision-making and improve outcomes for people with multiple myeloma.
"Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study"
Source
Robert Z. Orlowski, Meletios A. Dimopoulos, Xavier Leleu, Thierry Facon, Tadao Ishida, Roman Hajek, Ivan Spicka, Joanna Romejko-Jarosinska, Vladimir I. Vorobyev, Britta Besemer, Sevgi Kalayoglu Besisik, Pawel Robak, Tomas Jelínek, Hartmut Goldschmidt, Thomas Martin, Mohamed Mohty, Sandrine Macé, Ercem Kodas, Christina Tekle, Andrea T Shafer, Philippe Moreau; Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study. Blood 2026; blood.2025030120. doi: https://doi.org/10.1182/blood.2025030120 March 2, 2026.
Overview
The Phase 3 IMROZ study evaluated a four-drug combination—isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd)—followed by maintenance with isatuximab, lenalidomide, and dexamethasone (Isa-Rd) in patients with newly diagnosed multiple myeloma who were not eligible for transplant. Compared with the standard three-drug regimen of bortezomib, lenalidomide, and dexamethasone (VRd) followed by Rd, patients receiving Isa-VRd/Isa-Rd achieved deeper responses, with higher rates of minimal residual disease (MRD) negativity and MRD-negative complete response throughout both the initial and maintenance phases.
These benefits were seen across key patient groups, including older adults and those considered frail. Patients who converted from MRD-positive to MRD-negative experienced a longer time before their disease progressed, and even those who shifted from MRD-negative to MRD-positive still showed better outcomes with the quadruplet regimen compared with VRd/Rd. Tracking MRD at multiple points during treatment may therefore help doctors make better decisions about continuing or adjusting therapy.
Overall, the IMROZ study shows that Isa-VRd/Isa-Rd provides deeper and more sustained responses than standard therapy, supporting its use as a front-line treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma.
"Summary of Research: Elranatamab Fixed Dosing—A Safe, Effective, and Convenient Dosing Approach"
Source
Elmeliegy, M., Soltantabar, P., Hibma, J. et al. Summary of Research: Elranatamab Fixed Dosing—A Safe, Effective, and Convenient Dosing Approach. Oncol Ther (2026). https://doi.org/10.1007/s40487-026-00415-0 March 2, 2026.
Overview
This study looked at whether body weight affects how well elranatamab works or how safe it is for people with multiple myeloma. Data came from the MagnetisMM-3 trial, where all participants received the same fixed dose of 76 mg of elranatamab, regardless of their weight. Participants were divided into four weight groups to see if there were any differences in how the drug behaved in the body, the side effects experienced, or the treatment responses.
The results showed that elranatamab worked well across all weight groups, with similar rates of response. Side effects were also comparable, and there were no meaningful differences in how the drug was processed in the body. These findings suggest that a fixed dose of elranatamab is both safe and effective for people of different body weights, making treatment simpler and easier to manage.
"Efficacy and Safety of Belantamab Mafodotin with Bortezomib Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: the DREAMM-6 Arm B Trial"
Source
Rakesh Popat, Bradley Augustson, Paul Cannell, Keith Stockerl-Goldstein, Andrew Spencer, Amit Khot, Ajay Nooka, Nashita Patel, Ravi S. Kasinathan, Astrid McKeown, Amy Curry, Rachel Rogers, Mehreen Shaikh, Fernando Carreno, Sumita Roy-Ghanta, Joanna Opalinska, Hang Quach; Efficacy and Safety of Belantamab Mafodotin with Bortezomib Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: the DREAMM-6 Arm B Trial. Clin Cancer Res 2026; https://doi.org/10.1158/1078-0432.CCR-25-3216 March 2, 2026.
Overview
The Phase 1/2 DREAMM-6 Arm B study tested the combination of belantamab mafodotin with bortezomib and dexamethasone (BVd) in patients with relapsed or refractory multiple myeloma who had already received several prior treatments. Patients received different dosing schedules of belantamab mafodotin to see which was safest and most effective, while all received standard doses of bortezomib and dexamethasone.
Among 107 patients, the overall response rate was 70%, showing that the combination was effective even in heavily pretreated patients. The most common serious side effect involved the eyes, with changes in vision or corneal health reported in the majority of patients, though these events were generally manageable. Higher drug exposures were linked to deeper responses but also increased the likelihood of eye-related side effects, while lower doses were associated with slightly fewer responses and fewer eye issues.
Overall, the study found that BVd has manageable safety and strong activity against multiple myeloma, supporting the 2.5 mg/kg every three weeks dosing as an effective treatment option for patients whose disease has returned or not responded to previous therapies..
"CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation"
Source
Simone Minnie, Kenneth Ho, Julie R Boiko, Rachael C Adams, Kathleen S. Ensbey, Nicole S Nemychenkov, Samuel RW Legg, Christine R Schmidt, Melissa L. Comstock, Justina Lyons, Tomoko Sekiguchi, Motoko Koyama, Andrew Spencer, Damian J Green, Geoffrey R Hill; CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation. Blood 2026; blood.2025030207. doi: https://doi.org/10.1182/blood.2025030207 March 2, 2026.
Overview
This study looked at why multiple myeloma sometimes relapses after autologous stem cell transplant (ASCT), even when patients receive maintenance lenalidomide. Researchers focused on certain immune cells in the bone marrow, specifically a type of macrophage marked by CD64, CD169, and CD163. These cells were more common in patients whose disease relapsed and carried proteins that can suppress immune responses, such as CSF-1R, PD-L1, and CD155.
In preclinical models, neither CSF-1R inhibition nor lenalidomide alone had a strong effect, but combining the two treatments slowed disease progression and extended survival. The study showed that lenalidomide increased NK-like CD8+ T cells, which can fight myeloma, but also increased the suppressive macrophages. These macrophages limited the activity of NK-like and exhausted CD8+ T cells through immune checkpoints like NKG2A and PD-1. Blocking CSF-1R removed these suppressive macrophages, reducing inhibitory signals and boosting T-cell activation.
These findings suggest that combining CSF-1R blockade with lenalidomide maintenance could improve outcomes after ASCT. Since drugs targeting CSF-1R, like axatilimab, are already approved for other conditions, this strategy could be tested in patients relatively quickly to help prevent relapse
"TCR T cells targeting IgA- and IgG-expressing multiple myeloma"
Source
Karolos Douvlataniotis, Aleksei Titov, Julia Zeun, Merve Bilici, Heyilimu Palashati, Waywen Loh, Even Holth Rustad, Weiwen Yang, Trung T Tran, Fridtjof Lund-Johansen, Ravi Chand Bollineni, Jessica D. Kepple, Luis P. Huth, Ludvig A Munthe, Thorstein Boxaspen, Fredrik Schjesvold, Anders Waage, Dimitrios L. Wagner, Katherine R. Bull, Joanna Hester, Fadi Issa, Eirini Giannakopoulou, Johanna Olweus; TCR T cells targeting IgA- and IgG-expressing multiple myeloma. Blood 2026; blood.2025031897. doi: https://doi.org/10.1182/blood.2025031897 March 2, 2026. .
Overview
This study explored a new way to target multiple myeloma using T cells. Researchers focused on the constant regions of immunoglobulins, the antibodies produced in excess by myeloma cells, which are not accessible to current CAR T-cell or antibody therapies. They found that these immunoglobulin regions are highly expressed in most patients, making them promising targets for engineered T-cell receptors (TCRs).
T cells were modified with TCRs that specifically recognize the constant regions of IgA or IgG. These engineered T cells were carefully tested for safety and selectively killed myeloma cells in lab studies from patients who produced the corresponding antibody type. In animal models, IgA-targeted TCR T cells eliminated IgA-positive myeloma cells and reduced antibody levels in the blood.
These results suggest that targeting immunoglobulin constant regions could provide a new therapy for about 40% of European-descent patients with multiple myeloma, and expanding the approach to other HLA types could make it available to even more patients. This strategy may also have potential applications for other cancers like lymphoma and certain autoimmune diseases, offering a new avenue for T-cell-based therapies.
"Accelerated synthesis of immunomodulatory imide drugs and their derivatives via continuous flow chemistry"
Source
Hou, T., Huang, J., Li, Y. et al. Accelerated synthesis of immunomodulatory imide drugs and their derivatives via continuous flow chemistry. Commun Chem (2026). https://doi.org/10.1038/s42004-026-01956-1 March 3, 2026.
Overview
This study focused on making two important multiple myeloma treatments, lenalidomide and pomalidomide, more efficiently. Current methods to produce these immunomodulatory drugs are often long and complicated. Researchers developed a continuous flow process that can make lenalidomide in 42 minutes and pomalidomide in 52 minutes, with yields of 63% and 62%, respectively.
The new method works on a gram scale and allows the drugs to be made without using time-consuming purification steps like column chromatography. Both drugs can be made from a shared intermediate, simplifying the production process. The researchers also applied the continuous flow approach to make derivatives called CRBN ligand-linkers, achieving yields over 90% and creating a variety of compounds with different properties.
Overall, this approach offers a faster, more efficient, and scalable way to produce key multiple myeloma drugs and related compounds, which could improve availability and support further drug development.
"Enhanced antitumoral activity of the academic CAR-T ARI0002h against normal and low BCMA-expressing myeloma cells after incorporating a transmembrane CD28 domain"
Source
Cardus O, Mañé Pujol J, de Daniel A, Moreno DF, Oliveira TGM, Battram AM, et al. Enhanced antitumoral activity of the academic CAR-T ARI0002h against normal and low BCMA-expressing myeloma cells after incorporating a transmembrane CD28 domain. Journal for ImmunoTherapy of Cancer. 2026;14:e011864. https://doi.org/10.1136/jitc-2025-011864 March 3, 2026.
Overview
This study looked at a new version of CAR-T cell therapy for multiple myeloma, a treatment that programs a patient’s T cells to attack cancer cells. Current CAR-T therapies targeting BCMA are effective, but many patients relapse because the cancer cells reduce BCMA expression or the CAR-T cells become exhausted. Researchers developed a modified CAR-T product, ARI2h-TM28, by changing a part of the CAR called the transmembrane domain to CD28, with the goal of improving effectiveness and durability.
In lab experiments, ARI2h-TM28 performed similarly to the original CAR-T cells in killing myeloma cells and producing immune signals, but it was better at targeting cells with low BCMA levels. In animal models, the modified CAR-T cells controlled tumor growth more effectively and improved survival. The new CAR-T cells also showed a stronger metabolic profile, meaning they were more energetic and less prone to exhaustion, which helps them persist longer and maintain their cancer-fighting activity.
Overall, this modification to the CAR-T design enhances tumor control, even in cases where the cancer has reduced BCMA, and supports more durable responses. These findings suggest that ARI2h-TM28 could offer a more potent and longer-lasting therapy for patients with relapsed or refractory multiple myeloma.
"Exercise-mobilized lymphocytes enhance antibody-based immunotherapy in multiple myeloma through CD16+ NK cell–mediated cytotoxicity"
Source
Chou, L., Valenzuela, A.M., McDougal, L.M. et al. Exercise-mobilized lymphocytes enhance antibody-based immunotherapy in multiple myeloma through CD16+ NK cell–mediated cytotoxicity. J Transl Med (2026). https://doi.org/10.1186/s12967-026-07888-7 March 3, 2026. .
Overview
This study explored whether exercise could boost immune responses against multiple myeloma and improve the effectiveness of existing therapies. Researchers looked at lymphocytes—immune cells collected from healthy participants at rest and after a 20-minute cycling session—and tested their ability to kill myeloma cells in the lab. They combined these cells with standard treatments, including lenalidomide and dexamethasone paired with either daratumumab (DRd) or magrolimab (MRd).
The results showed that exercise-mobilized lymphocytes were more effective at killing both drug-sensitive and drug-resistant myeloma cells than resting lymphocytes. The effect was strongest when combined with DRd or MRd. Exercise particularly increased the number of CD16+ natural killer (NK) cells, which are key for antibody-dependent cell killing. Blocking CD16 reduced this enhanced activity, showing that these NK cells were central to the effect. Exercise-mobilized NK cells also worked better in combination with MRd than DRd, likely because daratumumab can reduce certain NK cell populations.
Overall, the study suggests that acute exercise mobilizes a potent subset of NK cells that can enhance the effectiveness of antibody-based myeloma therapies. These findings highlight the potential for using carefully timed exercise as a complementary strategy to improve treatment outcomes in multiple myeloma.
"The Changing Landscape of Second Primary Malignancies in Multiple Myeloma: A SEER Population-Based Study Between Two Therapeutic Eras"
Source
Lu W, Huang X, Tian S, Liang X, Ke G, Guo J, Li Q, Huang Y, Li Y, Luo B, Lin B, Xu D, Wang L. The Changing Landscape of Second Primary Malignancies in Multiple Myeloma: A SEER Population-Based Study Between Two Therapeutic Eras. Cancer Control. 2026 Jan-Dec;33:10732748261432266. doi: 10.1177/10732748261432266. Epub 2026 Mar 4. 6.
Overview
This study looked at how the risk of second cancers has changed for people with multiple myeloma over time. Researchers analyzed data from nearly 27,000 patients in the SEER database, comparing two treatment eras: 1990–2005 (Era-1) and 2006–2021 (Era-2). They focused on patients who developed second primary malignancies (SPMs), which are new cancers that occur after the initial myeloma diagnosis.
The results showed that the overall risk of developing a second cancer was higher in Era-2, particularly for solid tumors, while the risk of blood cancers did not change significantly. Patients in Era-2 also developed second cancers sooner, with most occurring within about 7.5 years of the initial diagnosis. Survival among patients who developed SPMs did not improve between the two eras. Interestingly, patients who developed second cancers lived longer than those who did not, but this likely reflects survivor bias, since only patients who live long enough can develop SPMs.
These findings indicate that as treatments for multiple myeloma have improved and patients live longer, the risk of second cancers has increased and occurs sooner. This highlights the importance of ongoing cancer monitoring and early detection for survivors of multiple myeloma.
"DKC1: a robust prognostic factor and potential therapeutic target in multiple myeloma."
Source
Sun, C., Cheng, L., Li, A. et al. DKC1: a robust prognostic factor and potential therapeutic target in multiple myeloma. J Transl Med (2026). https://doi.org/10.1186/s12967-026-07916-6 March 4, 2026.
Overview
This study investigated the role of DKC1, a protein involved in RNA modification, in multiple myeloma. Researchers analyzed patient data and found that higher DKC1 levels were linked to worse outcomes, making it a potential marker for identifying high-risk patients. Laboratory experiments showed that DKC1 helps myeloma cells grow, survive, and form colonies. Blocking DKC1, either with genetic tools or a drug called pyrazofurin, slowed cell growth, increased cell death, and reduced tumor growth in mouse models.
Further analysis revealed that DKC1 works in part by stabilizing a gene called ATF5 through a chemical modification called pseudouridylation, which protects ATF5 mRNA from degradation. When DKC1 was blocked, ATF5 levels dropped, reducing myeloma cell proliferation and survival.
The study shows that DKC1 promotes multiple myeloma progression by supporting ATF5 and highlights DKC1 as both a potential biomarker for risk assessment and a promising target for new treatments.
"Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression"
Source
J. Jiang, L. Ren, Y. Sun, et al., “Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression,” Cancer Medicine 15, no. 3 (2026): e71651, https://doi.org/10.1002/cam4.71651. March 4, 2026.
Overview
This study investigated the effects of imeglimin (IME), a new oral anti-diabetic drug, on multiple myeloma cells. Researchers tested IME in lab-grown myeloma cell lines and in mouse models implanted with human myeloma cells. They also analyzed how the drug affected cell metabolism and gene expression, focusing on the role of IL-16, a molecule important in the bone marrow environment.
The results showed that IME slowed myeloma cell growth and tumor development by causing cell cycle arrest, stopping cells from dividing. The drug altered cell metabolism by reducing oxidative phosphorylation and increasing glycolysis, which led to higher lactate levels. IME also lowered IL-16 expression and changed several pathways involved in cytokine signaling, which may help disrupt the supportive environment myeloma cells rely on.
Overall, the findings suggest that IME could offer a new strategy to treat multiple myeloma by targeting both energy metabolism and IL-16 in the bone marrow, potentially limiting tumor growth and progression.
"Impact of Intensive Cyclophosphamide-containing multi-agent Bridging Therapy on Outcomes After Idecabtagene Vicleucel in Multiple Myeloma"
Source
Taku Kikuchi, Ukyo Kondo, Shotaro Sugita, Miyu Watanabe, Chiaki Matsumoto, Moe Nomura-Yogo, Kodai Kunisada, Kota Sato, Tomomi Takei, Yu Abe, Osamu Hosoya, Tadao Ishida, Nobuhiro Tsukada, Impact of Intensive Cyclophosphamide-containing multi-agent Bridging Therapy on Outcomes After Idecabtagene Vicleucel in Multiple Myeloma, Transplantation and Cellular Therapy, 2026, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2026.02.062. March 4, 2026.
Overview
This study looked at how intensive chemotherapy given before CAR-T therapy affects outcomes in patients with relapsed or refractory multiple myeloma. Some patients receive a “bridging therapy” while their CAR-T cells are being prepared, especially if their disease is aggressive. Researchers reviewed data from 94 patients who received idecabtagene vicleucel (ide-cel) and compared those who had intensive cyclophosphamide-containing chemotherapy with those who had less or no bridging therapy.
The results showed that while intensive bridging therapy delayed recovery of platelets and neutrophils, it did not independently affect progression-free survival once baseline disease severity was considered. Most patients experienced cytokine release syndrome (CRS) and few had severe neurotoxicity (ICANS), with no difference based on the intensity of bridging therapy. Serious infections were also similar across groups.
These findings suggest that intensive chemotherapy can be safely used as a bridging strategy for patients with aggressive myeloma needing disease control before CAR-T infusion, without significantly increasing the risk of serious side effects or reducing the effectiveness of CAR-T therapy.
"Selective B-cell subset depletion underlies increased infection risk in patients with MM treated with anti-BCMA vs anti-GPRC5D bsAbs"
Source
Tomas Jelinek, David Zihala, Aintzane Zabaleta, Ioannis V. Kostopoulos, Ondrej Soucek, Ondrej Venglar, Cristina Moreno, Despina Fotiou, Eva Radova, Luis Esteban Tamariz-Amador, Foteini Theodorakakou, Ludmila Muronova, Andrea Manubens, Ourania Tsitsilonis, Tereza Popkova, Carmen Gonzalez, Anjana Anilkumar Sithara, Francesco Corrado, Nayda Bidikian, Camila Guerrero, Veronika Kapustova, Daniel Bilek, Patrick R. Hagner, Marta Larrayoz, Jose A. Martinez Climent, Lucie Broskevicova, Jana Mihalyova, Maximilian Merz, Tereza Sevcikova, Irene M. Ghobrial, Jesus San Miguel, Meletios A. Dimopoulos, Paula Rodriguez-Otero, Jakub Radocha, Efstathios Kastritis, Bruno Paiva, Roman Hajek; Selective B-cell subset depletion underlies increased infection risk in patients with MM treated with anti-BCMA vs anti-GPRC5D bsAbs. Blood 2026; 147 (10): 1070–1082. doi: https://doi.org/10.1182/blood.2025029572 March 5, 2026.
Overview
This study explored why infections are more common and sometimes more severe in patients treated with certain bispecific antibody therapies for multiple myeloma. Researchers compared treatments targeting BCMA and GPRC5D, two different proteins found on myeloma cells, to understand how they affect the immune system.
They found that BCMA is present not only on myeloma cells but also on normal B cells at multiple stages of development, including early precursor cells. As a result, anti-BCMA therapies can significantly reduce both cancerous plasma cells and healthy B cells, including immature ones. In contrast, GPRC5D is mainly found on myeloma cells and some normal plasma cells, so treatments targeting GPRC5D have a more limited effect on the broader immune system.
Because B cells play an important role in fighting infections, their depletion with anti-BCMA therapy may explain the higher risk of infections seen in these patients. Overall, the findings suggest that different bispecific antibody treatments affect the immune system in different ways, and this information could help guide more personalized treatment choices to balance effectiveness and infection risk.
"Real-world outcomes of newly diagnosed multiple myeloma patients treated with front-line daratumumab bortezomib lenalidomide and dexamethasone"
Source
Parrondo RD, de Menezes R, Sledge H, Nayyar M, Yadav K, Bergsagel L, Fonseca R, Kapoor P, Buadi F, Gertz MA, Dispenzieri A, Roy V, Sher T, Binder M, Abdallah N, Chhabra S, Rajkumar VS, Gonsalves WI, Cook J, Dingli D, Lin Y, Fernandez A, Flott C, Yadav U, Warsame RM, Wiedmeier-Nutor EE, Kourelis T, Leung N, Siddiqui MA, Kumar S, Chanan-Khan AA, Ailawadhi S. Real-world outcomes of newly diagnosed multiple myeloma patients treated with front-line daratumumab bortezomib lenalidomide and dexamethasone. Haematologica; https://doi.org/10.3324/haematol.2025.300401 [Early view]. March 5, 2026.
Overview
This real-world study looked at how a four-drug combination—daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd)—works for patients with newly diagnosed multiple myeloma. Researchers reviewed records from more than 400 patients treated across multiple centers and compared their outcomes to results from the Phase 3 PERSEUS clinical trial. They also examined how the treatment was used in everyday practice, including dosing, transplant use, and maintenance therapy.
The results showed that DVRd was highly effective, with most patients responding to treatment and many achieving deep responses, including minimal residual disease (MRD) negativity. Outcomes for patients who received a stem cell transplant were especially strong, with high rates of disease control at two and three years. Importantly, patients who achieved MRD negativity had longer periods without disease progression. The study also found that giving bortezomib once weekly, which is common in real-world practice, worked just as well as twice-weekly dosing.
For patients who did not undergo transplant, responses were still good, although progression-free survival was shorter compared to those who had a transplant. After relapse, second-line treatments remained effective, with most patients responding again.
This study shows that DVRd is an effective first-line treatment in real-world settings, with results similar to those seen in clinical trials. It also highlights how treatment approaches can vary in practice, while still achieving strong outcomes, and supports the use of DVRd with or without transplant for patients with newly diagnosed multiple myeloma.
"Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis–Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation"
Source
Sun X, Zhou Y, Wang Y, Dai Y, Zhu W, Chen H. Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis–Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation. JMIR Res Protoc 2026;15:e86322 doi: 10.2196/86322 March 5, 2026.
Overview
This study describes an ongoing clinical trial examining whether a Traditional Chinese Medicine (TCM) herbal formula can improve outcomes for people with multiple myeloma when combined with standard treatment. In TCM, myeloma is often linked to patterns such as “kidney deficiency,” “phlegm,” and “blood stasis.” Researchers believe these patterns may relate to changes in the immune system within the bone marrow. The trial focuses on whether a specific herbal approach—the kidney-tonifying, phlegm-resolving, and blood stasis–removing (KPR) method—can influence an epigenetic pathway (PHF19-EZH2-H3K27me3) that is thought to play a role in myeloma progression and immune dysfunction.
In this randomized controlled trial, patients are assigned to one of three groups: a control group, a group receiving standard Western therapy, or a group receiving both standard bortezomib-based treatment and the KPR herbal formula. Treatment lasts 12 weeks, followed by six months of follow-up. Researchers will measure immune changes—especially CD3+ T cells—as the main outcome, along with disease markers, laboratory tests, imaging, and symptom scores.
The trial began enrollment in 2025 and is still underway, with results expected in the coming years. If the study confirms that the KPR approach improves the immune microenvironment through this epigenetic pathway, it could provide scientific support for integrating certain TCM therapies with modern myeloma treatment, particularly for patients with relapsed or refractory disease.
"Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis–Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation"
Source
Sun X, Zhou Y, Wang Y, Dai Y, Zhu W, Chen H. Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis–Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation. JMIR Res Protoc 2026;15:e86322 doi: 10.2196/86322 March 5, 2026.
Overview
This study describes an ongoing clinical trial testing whether a Traditional Chinese Medicine (TCM) herbal formula can improve treatment outcomes for people with multiple myeloma when added to standard therapy. In TCM, myeloma is associated with patterns like “kidney deficiency,” “phlegm,” and “blood stasis,” which researchers believe may reflect changes in the immune system. The study focuses on a specific herbal approach called the kidney-tonifying, phlegm-resolving, and blood stasis–removing (KPR) method and how it may affect an epigenetic pathway (PHF19-EZH2-H3K27me3) linked to myeloma growth and immune dysfunction.
In this randomized trial, patients are assigned to one of three groups: a control group, a group receiving standard bortezomib-based treatment, or a group receiving both standard treatment and the KPR herbal formula. Treatment lasts 12 weeks, followed by six months of follow-up. Researchers are measuring immune changes—especially levels of CD3+ T cells—as the main outcome, along with disease markers, lab tests, imaging, and symptom scores.
The study is currently ongoing, with patient enrollment underway and results expected in the coming years. If successful, the findings could provide scientific evidence for combining certain TCM approaches with modern treatments, potentially offering a new option to improve immune function and outcomes in patients with relapsed or refractory multiple myeloma.
"REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials"
Source
Uttervall K, Kortum MK, Perrot A, Farmer SL, Cavo M, Kishore B, Jacquet C, Casanova M, Hansson M, Weisel K, Magen H, Liberatore C, Hansen CT, Gatt ME, Shragai T, Da Via MC, Alvarez TDS, Streetly M, Raab MS, Manier S, Aegesen J, Albrecht C, Hu P, Smirnov P, Santra D, Rubio-Azpeitia E, Popat R. REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials. Haematologica; https://doi.org/10.3324/haematol.2025.289281 [Early view]. March 5, 2026.
Overview
This study looked at how well teclistamab works in real-world patients with relapsed or refractory multiple myeloma who have already received several prior treatments. Teclistamab is a bispecific antibody that targets BCMA and is approved based on clinical trial results, but this study evaluated its use outside of trials across multiple countries. Most patients had very advanced disease, with many no longer responding to standard drug classes and some having already received prior BCMA-targeted therapy.
The results showed that about 60% of patients responded to teclistamab, and over half achieved a deep response. These responses were durable, with many patients maintaining disease control for extended periods. Patients who achieved deeper responses had better outcomes, including longer time without disease progression and improved overall survival. Importantly, the treatment worked across different patient groups, including those with more aggressive disease.
Side effects were consistent with what has been seen in clinical trials. The most common were infections, cytokine release syndrome, and low blood counts. While infections were common, they tended to decrease over time, and many patients received immunoglobulin replacement to help support their immune system.
This real-world study confirms that teclistamab is an effective treatment option for heavily pretreated patients with multiple myeloma, with manageable side effects and meaningful, lasting responses.
"Rate of MGUS Progression to Haematological Malignancies: A Systematic Review"
Source
Quinn SJ, Cardwell C, Anderson LA, McShane C. Rate of MGUS Progression to Haematological Malignancies: A Systematic Review. Eur J Haematol. 2026 Mar 5. doi: 10.1111/ejh.70086. Epub ahead of print. PMID: 41787687.
Overview
This study reviewed data from many previous studies to better understand how often monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or other blood cancers. MGUS is a common, symptom-free condition that can come before myeloma, and it is often described as having about a 1% per year risk of becoming cancer.
By analyzing results from 46 studies across 17 countries, the researchers found that, on average, about 1.2% of people with MGUS per year developed a blood cancer, and about 0.8% per year developed multiple myeloma specifically. These findings are generally in line with current guidelines. However, the study also found that reported progression rates varied widely between studies, depending on factors like patient populations, follow-up time, and study design.
Because of this variation, the authors suggest that risk estimates should be interpreted with caution. While MGUS remains a low-risk condition for most people, the likelihood of progression may differ from person to person, highlighting the need for ongoing monitoring and more personalized risk assessment.
"Daratumumab-based second line therapy improves outcomes after VRD induction, upfront autologous transplant and lenalidomide maintenance"
Source
Oren Pasvolsky, Curtis Marcoux, Denái R. Milton, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Umer R. Siddiqui, Hina N Khan, Asad A. Haider, Jeremy Ramdial, Yago Nieto, Guilin Tang, Kiran Lakhani, Yosra Aljawai, Partow Kebriaei, Hans C. Lee, Krina K. Patel, Sheeba K. Thomas, Robert Z. Orlowski, Richard E. Champlin, Elizabeth J. Shpall, Muzaffar H. Qazilbash, Daratumumab-based second line therapy improves outcomes after VRD induction, upfront autologous transplant and lenalidomide maintenance, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.02.014. March 5, 2026.
Overview
This study looked at treatment options after relapse in patients with multiple myeloma who initially received standard therapy with bortezomib, lenalidomide, dexamethasone, stem cell transplant, and lenalidomide maintenance. Researchers reviewed outcomes for patients who later needed second-line treatment to see which approaches worked best.
They found that patients who received daratumumab-based combinations in the second-line setting had better outcomes than those treated with other common regimens. These patients were more likely to achieve deep responses and had a much longer time before their disease progressed again—nearly five years on average—compared with about one year for other treatments.
The study also showed that patients whose disease relapsed later after transplant tended to live longer, while those with more aggressive relapse had worse outcomes.
These findings suggest that daratumumab-based therapies are an effective second-line option after standard first-line treatment and may provide longer-lasting disease control for patients with relapsed multiple myeloma.
"Discordance between immunofixation and free light chain assays in multiple myeloma: a retrospective analysis and evaluation of the heavy/light chain assay for disease monitoring"
Source
Nathalang, O., Onthong, Y., Laoruangroj, C. et al. Discordance between immunofixation and free light chain assays in multiple myeloma: a retrospective analysis and evaluation of the heavy/light chain assay for disease monitoring. Blood Res. (2026). https://doi.org/10.1007/s44313-026-00130-9 March 6, 2026.
Overview
This study looked at how well different blood tests agree when measuring monoclonal proteins in multiple myeloma. Standard tests, such as immunofixation (SIFE) and serum-free light chain (SFLC) testing, are commonly used to monitor disease, but they do not always give matching results, especially when protein levels are low. Researchers analyzed over 1,300 patient samples to better understand these differences and to evaluate another test called the heavy/light chain (HLC) assay.
They found that about 27% of samples showed disagreement between SIFE and SFLC results. This mismatch was common in certain situations, such as in patients with light chain myeloma or those who had already responded well to treatment. The HLC test showed strong agreement with some standard measures and aligned well with SIFE results, but not with SFLC. In some cases, using HLC testing changed how patients’ responses were classified, suggesting that standard methods may sometimes overestimate how well treatment is working.
Overall, the findings show that no single test gives a complete picture. Adding HLC testing may help clarify unclear or conflicting results and improve how doctors track disease and assess treatment response in multiple myeloma.
"Prophylactic Immunoglobulin Supplementation for Infection Prevention in Multiple Myeloma: An Updated Systematic Review and Meta-Analysis"
Source
Akihiro Miyashita, Shunsuke Kondo, Kensuke Takaoka, Yoshito Nishimura, Thomas Rodgers, Prophylactic Immunoglobulin Supplementation for Infection Prevention in Multiple Myeloma: An Updated Systematic Review and Meta-Analysis, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.002. March 6, 2026.
Overview
This study looked at whether giving preventive immunoglobulin (Ig) treatment can reduce infections in people with multiple myeloma. Patients with myeloma often have a higher risk of infections because both the disease and its treatments can weaken the immune system. Researchers reviewed results from 10 studies, including more than 2,300 patients, to compare outcomes in those who received Ig supplementation versus those who did not.
The findings showed that patients who received Ig had a lower rate of serious infections compared to those who did not. However, there was no clear difference in the overall number of infections or in overall survival between the two groups. This suggests that while Ig may help prevent more severe infections, it may not reduce all infections or extend survival.
The study supports the use of preventive immunoglobulin in reducing the risk of serious infections in multiple myeloma, but more research is needed to confirm these benefits and better understand which patients are most likely to benefit.
"Prophylactic Immunoglobulin Supplementation for Infection Prevention in Multiple Myeloma: An Updated Systematic Review and Meta-Analysis"
Source
Akihiro Miyashita, Shunsuke Kondo, Kensuke Takaoka, Yoshito Nishimura, Thomas Rodgers, Prophylactic Immunoglobulin Supplementation for Infection Prevention in Multiple Myeloma: An Updated Systematic Review and Meta-Analysis, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.002. March 6, 2026.
Overview
This study looked at whether giving preventive immunoglobulin (Ig) treatment can reduce infections in people with multiple myeloma. Patients with myeloma often have a higher risk of infections because both the disease and its treatments can weaken the immune system. Researchers reviewed results from 10 studies, including more than 2,300 patients, to compare outcomes in those who received Ig supplementation versus those who did not.
The findings showed that patients who received Ig had a lower rate of serious infections compared to those who did not. However, there was no clear difference in the overall number of infections or in overall survival between the two groups. This suggests that while Ig may help prevent more severe infections, it may not reduce all infections or extend survival.
The study supports the use of preventive immunoglobulin in reducing the risk of serious infections in multiple myeloma, but more research is needed to confirm these benefits and better understand which patients are most likely to benefit.
"Advances in the application of frailty scoring in the diagnosis and management of elderly patients with multiple myeloma (Review)"
Source
Liu, J., Li, D., Li, C., & Chen, Z. (2026). Advances in the application of frailty scoring in the diagnosis and management of elderly patients with multiple myeloma (Review). Oncology Reports, 55, 88. https://doi.org/10.3892/or.2026.9093 March 6, 2026.
Overview
This review examines the role of frailty in older adults with multiple myeloma (MM), a blood cancer that disproportionately affects elderly populations. Frailty—a condition marked by reduced physiological reserve and increased vulnerability to stressors—has a major impact on diagnosis, treatment choices, and outcomes in MM. The review explains how chronic inflammation, muscle loss (sarcopenia), and immune dysfunction contribute to both frailty and worse MM outcomes.
Clinically, frail patients are more likely to experience treatment toxicity, longer hospital stays, and lower survival. Tools such as the International Myeloma Working Group frailty score and comprehensive Geriatric Assessments help identify frail patients and guide personalized treatment strategies. Advances in frailty scoring allow for more precise risk stratification, helping clinicians balance therapy effectiveness with safety.
The review also discusses challenges in routinely assessing frailty in clinical practice and highlights future directions, including the development of new biomarkers and digital tools to improve monitoring and decision-making. Overall, integrating frailty assessment into MM care can help optimize outcomes and support individualized treatment for older patients.
"Metabolically Silent Diffuse Hepatic Involvement in Multiple Myeloma: An 18F-FDG-PET/CT Pitfall. Mol Imaging"
Source
Bilgiç S, Okuyan M, İbrahim E. Metabolically Silent Diffuse Hepatic Involvement in Multiple Myeloma: An 18F-FDG-PET/CT Pitfall. Mol Imaging Radionucl Ther. 2026 Mar 6. doi: 10.4274/mirt.galenos.2026.09475. Epub ahead of print.
Overview
This case report describes a 59-year-old man with a 3-year history of multiple myeloma (MM) who developed progressive hepatomegaly and perihepatic ascites. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed marked diffuse liver enlargement but no hepatic 18F-FDG uptake, despite mild skeletal uptake indicating a low–FDG–avid myeloma phenotype. Because of this mismatch between liver morphology and metabolic activity, a liver biopsy was performed, revealing diffuse sinusoidal infiltration by CD138-positive, lambda-restricted plasma cells and excluding hepatic amyloidosis. After systemic therapy, hepatomegaly and ascites improved, but hepatic FDG uptake remained absent.
This case underscores a key limitation of 18F-FDG PET/CT in detecting diffuse hepatic myeloma and highlights the importance of combining imaging with histopathology and other diagnostic approaches for accurate assessment in MM patients.
"The evolution of CAR T-cell, bispecific antibodies and antibody drug conjugates for the treatment of multiple myeloma"
Source
Lorenzo Cani, Richa Parikh, Nisha S. Joseph, Vikas A. Gupta, Craig C. Hofmeister, Jonathan L. Kaufman, Ajay K. Nooka, Sagar Lonial, Roberto Mina, The evolution of CAR T-cell, bispecific antibodies and antibody drug conjugates for the treatment of multiple myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.003. March 6, 2026.
Overview
New immune-based treatments are changing how doctors treat multiple myeloma. These therapies—like CAR T-cell therapy, bispecific antibodies, and antibody-drug conjugates—can help patients achieve deeper responses and live longer.
Originally used for patients whose cancer returned, these treatments are now being studied earlier in the disease, even at diagnosis. Researchers are also developing newer approaches, such as therapies that target multiple markers at once or combine different immune treatments.
While these therapies are powerful, they can cause serious side effects. These include immune reactions (like cytokine release syndrome), nerve-related symptoms, infections, and eye problems with certain drugs.
This research shows that immune therapies are becoming a central part of myeloma treatment. The next step is to better manage side effects and determine the best order and combinations of these treatments to improve long-term outcomes.
"A radiomics-driven approach for predicting response to induction therapy in multiple myeloma: Leveraging CT-based delta feature"
Source
Zhonghui Qu, Xiaobin Zhao, Man He, Xueying Zhang, Haoyu Wang, Zhixin Cui, A radiomics-driven approach for predicting response to induction therapy in multiple myeloma: Leveraging CT-based delta features, European Journal of Radiology, 2026, 112779, ISSN 0720-048X, https://doi.org/10.1016/j.ejrad.2026.112779. March 6, 2026.
Overview
This study developed a new imaging-based tool to better measure how patients with multiple myeloma respond to treatment. Researchers used CT scans taken before and after therapy to track subtle changes in bone areas like the ribs and spine—changes that may not be visible to the human eye.
By analyzing these changes with advanced data techniques (called “radiomics”), the model was able to predict treatment response more accurately than using single imaging areas alone. The combined, multi-region approach performed best and remained reliable when tested in a separate group of patients.
Although a standard lab test (24-hour urine protein) was included for context, the imaging-based model was the strongest predictor. Overall, this approach offers a non-invasive and more precise way to monitor treatment response and could help guide more personalized therapy decisions.
"Antibiotic-associated dysbiosis and bispecific antibody outcomes in multiple myeloma. Journal for ImmunoTherapy of Cancer"
Source
Corona M, García-Vicente R, Saez-Marin AJ, Ancos-Pintado R, Rodríguez-Garcia A, Arroyo A, et al. Antibiotic-associated dysbiosis and bispecific antibody outcomes in multiple myeloma. Journal for ImmunoTherapy of Cancer. 2026;14:e014224. https://doi.org/10.1136/jitc-2025-014224 March 6, 2026.
Overview
This study looked at how antibiotics affect outcomes in people with multiple myeloma receiving bispecific antibody (BsAb) therapy. Researchers found that patients who took broad-spectrum antibiotics before starting treatment had worse survival, faster disease progression, and a higher risk of relapse.
Antibiotics disrupted the gut microbiome by reducing helpful bacteria that produce short-chain fatty acids—molecules that support immune function. These patients also had fewer key immune cells and weaker immune signaling, which may explain their poorer outcomes.
The findings suggest that unnecessary antibiotic use before immunotherapy could reduce treatment effectiveness. Careful antibiotic use and strategies to protect the gut microbiome may help improve outcomes for patients receiving BsAb therapy.
"Reduced dose versus standard melphalan conditioning for autologous stem cell transplantation in multiple myeloma: a single-center retrospective study"
Source
Yao, Y., Zhang, S., Li, Z. et al. Reduced dose versus standard melphalan conditioning for autologous stem cell transplantation in multiple myeloma: a single-center retrospective study. Ann Hematol 105, 163 (2026). https://doi.org/10.1007/s00277-026-06909-1 March 6, 2026.
Overview
This study looked at whether a lower dose of chemotherapy (melphalan) is a safe and effective option for multiple myeloma patients who cannot tolerate the standard high dose before stem cell transplant.
Researchers found that even though patients receiving the lower dose were generally older or less healthy, their survival outcomes were similar to those who received the full dose. At the same time, the lower-dose group experienced fewer side effects, such as mouth sores, infections with fever, and slow platelet recovery.
Reduced-dose melphalan appears to be a safer alternative that still works well, especially for patients who are more fragile or have other health concerns.
"The [18F]FDG PET/CT for prognostic stratification in multiple myeloma: A systematic review and meta-analysis"
Source
Xiao, M., Sun, Y., Chen, Y. et al. The [18F]FDG PET/CT for prognostic stratification in multiple myeloma: A systematic review and meta-analysis. Eur J Nucl Med Mol Imaging (2026). https://doi.org/10.1007/s00259-026-07830-5 March 7, 2026.
Overview
This study reviewed many previous studies to understand whether PET/CT scans can help predict outcomes in people with multiple myeloma before treatment starts.
The results showed that certain scan findings—such as cancer outside the bone marrow, higher tumor activity, and a greater number of bone lesions—were linked to shorter survival and faster disease progression. Other measures of total tumor burden also showed potential for predicting risk.
PET/CT scans may be a valuable tool for identifying higher-risk patients early, helping doctors better predict outcomes and tailor treatment plans.
"Risk factors for venous thromboembolism in newly diagnosed multiple myeloma patients based on thrombosis prophylaxis"
Source
Zhao, S., Wang, Y., Jia, J. et al. Risk factors for venous thromboembolism in newly diagnosed multiple myeloma patients based on thrombosis prophylaxis. Ann Hematol 105, 166 (2026). https://doi.org/10.1007/s00277-026-06920-6 March 7, 2026.
Overview
Doctors studied 309 people newly diagnosed with multiple myeloma to find out which ones were more likely to develop dangerous blood clots — a condition called venous thromboembolism, or VTE. Blood clots can form in the legs or travel to the lungs, so knowing who is at higher risk helps doctors take steps to prevent them.
The study found six things that raised the risk of blood clots: older age, being immobile for three or more days, a high level of a protein called D-dimer in the blood, reduced kidney function, and two specific treatments — the chemotherapy drug doxorubicin and a combination of high-dose dexamethasone (a steroid) with a class of drugs called immunomodulators. Two things lowered the risk: blood thinners taken from the start of treatment, and anti-clotting medications like aspirin.
Age also changed how much some risk factors mattered. Poor kidney function was more dangerous in older patients than in younger ones. The high-dose steroid and immunomodulator combination raised clot risk in younger patients but did not show the same effect in older patients.
"Clinical utility and reproducibility of standardized PET-CT criteria in multiple myeloma: real-world implementation and prognostic relevance"
Source
Bharadwaj, P., Veeralakshmanan, P., Subramanyam, P. et al. Clinical utility and reproducibility of standardized PET-CT criteria in multiple myeloma: real-world implementation and prognostic relevance. Egypt J Radiol Nucl Med 57, 44 (2026). https://doi.org/10.1186/s43055-026-01711-5 March 7, 2026.
Overview
People with multiple myeloma often have areas of bone damage caused by the disease. Doctors use several types of scans to find and track these areas, including a scan called PET/CT, which uses a small amount of radioactive sugar to highlight active disease in the body.
A scoring system called IMPeTUs was developed in Italy in 2016 to give doctors a consistent way to read these PET/CT scans in multiple myeloma. This study tested whether two doctors, reading the same scans independently, would score them the same way — and whether those scores matched up with how patients were actually doing.
Twenty-one people newly diagnosed with multiple myeloma had PET/CT scans taken before chemotherapy and again about two weeks after finishing it. Two nuclear medicine specialists scored each scan without knowing what the other had written.
Their scores matched closely for most findings. For areas of bone damage and individual spots of disease, agreement was strong. For fractures, the two doctors agreed on every case. The only area where they diverged was in disease that had spread just outside the bone or into soft tissue — that type of lesion was harder to score consistently, especially on the second scan.
The results suggest that when doctors use the IMPeTUs system to read PET/CT scans, they reach similar conclusions in most situations. This matters for patients because treatment decisions in multiple myeloma often depend on what the scans show.
"Superenhancer-driven SMC4 promotes myeloma growth by epigenetically enhancing IFI16-dependent STING signaling"
Source
Guan, J., Lin, X., Dai, Z. et al. Superenhancer-driven SMC4 promotes myeloma growth by epigenetically enhancing IFI16-dependent STING signaling. Apoptosis 31, 92 (2026). https://doi.org/10.1007/s10495-026-02304-3 March 7, 2026.
Overview
Researchers studying myeloma cells identified a protein called SMC4 that appears to help the cancer grow. SMC4 is switched on by a type of genetic control element — essentially a region of DNA that turns certain genes up to high volume. When the researchers blocked SMC4 in lab-grown myeloma cells, the cells stopped multiplying as quickly and lost their ability to form new colonies.
The team then looked at how SMC4 produces that effect. They found it works by amplifying a signaling chain inside the cell that involves two other proteins, IFI16 and STING. When SMC4 is active, it turns up IFI16 and STING, which in turn produce inflammatory signals that make the environment around myeloma cells more favorable for their growth.
When the researchers used a drug to block the IFI16-STING pathway directly, it reversed the growth advantage that SMC4 had created.
The findings describe a previously unknown mechanism that myeloma cells appear to use to sustain themselves. The researchers suggest that drugs targeting this pathway could be worth investigating as a treatment approach, though this work was conducted in cell models and has not yet been tested in patients.
"Cardiac Amyloidosis AI-ECG Model is Useful in Predicting Outcomes in Multiple Myeloma Patients Without Amyloidosis Undergoing Autologous Stem Cell Transplant"
Source
Tan, Melinda S. Y., Gertz, Morie A., Muchtar, Eli, Buadi, Francis K., Kumar, Shaji K., Dingli, David, Gonsalves, Wilson I., Hayman, Suzanne, Kapoor, Prashant, Kourelis, Taxiarchis, Warsame, Rahma, Dasari, Surendra, Cook, Joselle, Attia, Zachi I., AbouEzzeddine, Omar F., Borgeson, Daniel D., Friedman, Paul A., Murphree, Dennis H., Lopez-Jimenez, Francisco, Grogan, Martha, Dispenzieri, Angela, Cardiac Amyloidosis AI-ECG Model is Useful in Predicting Outcomes in Multiple Myeloma Patients Without Amyloidosis Undergoing Autologous Stem Cell Transplant, Advances in Hematology, 2026, 3919126, 7 pages, 2026. https://doi.org/10.1155/ah/3919126 March 8, 2026.
Overview
Multiple myeloma can sometimes lead to a separate condition called AL amyloidosis, where abnormal proteins produced by the cancer build up in organs such as the heart. This complication is often missed early because its symptoms — fatigue, swelling, shortness of breath — overlap with many other conditions. By the time it is diagnosed, it has frequently caused serious damage.
Researchers tested whether an AI tool that reads electrocardiograms (ECGs, the standard heart electrical tracing) could identify myeloma patients at risk for this complication before symptoms appeared. The tool, called CA-AI-ECG, was developed to detect patterns in ECG readings associated with cardiac amyloidosis.
The study looked at 2,934 people with multiple myeloma. Most — 81% — had a stem cell transplant within 12 months of diagnosis and had an ECG taken around that time. In that group, a positive CA-AI-ECG result did not predict shorter survival. Among patients who had their transplant later, however, a positive result was associated with lower overall survival, and that relationship held up even after accounting for other health factors. The researchers think the difference may be explained by longer exposure to the abnormal proteins before treatment, which gives amyloid more time to accumulate.
During follow-up, 25 patients developed AL amyloidosis. Those with a positive CA-AI-ECG result before their transplant were five times as likely to develop the systemic form of the disease as those with a negative result.
The findings suggest the tool could help identify myeloma patients who need closer monitoring for amyloidosis, particularly those whose treatment is delayed.
"Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma"
Source
Ma, J., Gao, S., Liu, S. et al. Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma. Clin Exp Med (2026). https://doi.org/10.1007/s10238-026-02113-7 March 8, 2026.
Overview
Researchers analyzed tumor samples from 20 myeloma patients — 10 newly diagnosed, 2 in remission, and 8 whose disease had relapsed — using a technique called single-cell RNA sequencing, which reads the activity of genes in thousands of individual cells simultaneously. The dataset contained just over 60,000 cells, sorted into 12 cell types.
Comparing newly diagnosed and relapsed samples, the researchers found that relapsed myeloma had more T cells overall but fewer of the type that attack cancer. The CD8+ T cells — sometimes called killer T cells — were present but functionally impaired, meaning they had lost much of their ability to destroy myeloma cells. At the same time, a suppressive cell type called regulatory T cells had increased, which further reduces the immune response against the cancer.
A signaling protein called MIF emerged as a central factor in these changes. In relapsed samples, MIF activity was elevated, and it appeared to drive communication between the myeloma cells and the dysfunctional CD8+ T cells. The researchers confirmed higher MIF levels in relapsed tissue using two additional lab methods.
The findings point to MIF signaling and CD8+ T cell dysfunction as potential targets for treatments aimed at preventing or reversing myeloma relapse, though this work was conducted in tissue samples and has not yet been tested as a therapeutic strategy in patients.
"Incidence and mortality of multiple myeloma: Global, regional and national estimates and projections from the Global Burden of Disease Study"
Source
Qu F, Hui M, Yang F, He Y, Wang X. Incidence and mortality of multiple myeloma: Global, regional and national estimates and projections from the Global Burden of Disease Study 2021. Br J Haematol. 2026; 00: 1–9. https://doi.org/10.1111/bjh.70415 March 8, 2026.
Overview
Researchers used data from the Global Burden of Disease 2021 study — which tracks illness and death across 204 countries — to examine how rates of myeloma diagnosis, death, and disease burden have changed since 1990 and to project trends through 2050.
Between 1990 and 2021, the number of new myeloma diagnoses rose moderately worldwide. The increase was most pronounced in older adults and in wealthier countries. Men saw larger increases than women, and some middle-income regions — including parts of East Asia, Central Asia, and western sub-Saharan Africa — also recorded notable rises.
Death rates told a different story. Overall mortality grew only slightly over the period, and in women — particularly in high-income countries — age-adjusted death rates fell. The researchers attribute part of this pattern to the countries with the highest development indexes showing the slowest growth in new cases and deaths over time, likely reflecting better access to newer treatments.
One finding that ran in the opposite direction: the share of myeloma deaths and disease burden linked to high body mass index increased across all regions from 1990 to 2021.
Projections through 2050 suggest diagnosis rates will continue rising for both men and women. Death rates and overall disease burden are expected to climb among men, while trends in women remain more favorable.
"Targeting Metabolic Reprogramming in Multiple myeloma: molecular mechanisms and potential therapeutic targets"
Source
Xueting Zhu, Yikun Wang, Yizi He, Yajun Li, Caiqin Wang, Ruolan Zeng, Qianying Ouyang, Chang Su, Qianyu Hu, Guige Lu, Ling Xiao, Hui Zhou, Targeting Metabolic Reprogramming in Multiple myeloma: molecular mechanisms and potential therapeutic targets, Critical Reviews in Oncology/Hematology, 2026, 105257, ISSN 1040-8428, https://doi.org/10.1016/j.critrevonc.2026.105257. March 8, 2026.
Overview
In multiple myeloma, newer treatments, including proteasome inhibitors and immunotherapies, have improved outcomes, but the cancer frequently develops resistance and returns.
One reason resistance develops is that myeloma cells alter how they produce and use energy — a process researchers call metabolic reprogramming. This review article examined the evidence on how myeloma cells change five major metabolic pathways: glucose, fat, amino acid, nucleotide, and trace element metabolism (specifically iron and copper). The authors also looked at how bacteria living in the gut may influence myeloma progression through the chemical signals they produce.
The review argues that these metabolic changes do not occur in isolation. Instead, they form a connected network that helps myeloma cells grow, avoid the immune system, and resist drugs. The specific combination of changes varies depending on a patient's genetic makeup, the environment inside the bone marrow, and which treatments the cancer has already been exposed to.
The authors propose that identifying these metabolic patterns could add useful information beyond what current staging systems capture — potentially helping doctors predict which patients are at higher risk of relapse or which treatments are less likely to work. Several metabolic targets identified in the review are being investigated as possible treatment approaches, though none of the metabolism-based strategies discussed have yet reached routine clinical use.
"Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma"
Source
Kropp, E.M., Matono, S., Wang, O.Y. et al. Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma. Cell Death Dis (2026). https://doi.org/10.1038/s41419-026-08526-2 March 9, 2026.
Overview
Myeloma cells produce large amounts of abnormal protein and depend on a cellular disposal system called ERAD (endoplasmic reticulum-associated degradation) to prevent that protein from accumulating to toxic levels. Blocking ERAD has been explored as a way to kill myeloma cells, particularly those that have stopped responding to proteasome inhibitors — the backbone of most current myeloma treatment — but few effective ERAD-blocking drugs have been identified.
Researchers screened a library of FDA-approved and previously studied drugs to find compounds that block ERAD in myeloma cells. They identified omaveloxolone (also known as RTA408), a drug already in development for other conditions, as a potent ERAD inhibitor. In myeloma cells, it blocked the disposal of proteins inside and embedded in the endoplasmic reticulum without disrupting the breakdown of proteins elsewhere in the cell.
The researchers then traced how ERAD inhibition kills the cells. They expected cell death to follow from protein accumulation stress inside the endoplasmic reticulum, but instead found it was triggered by changes in the cell membrane that activated an external cell-death signaling chain involving a protein complex called DISC and an enzyme called caspase 8. This was an unexpected mechanism.
RTA408 killed myeloma cells taken directly from patients, including cells already resistant to proteasome inhibitors, and showed anti-myeloma activity in animal models.
The drug has not yet been tested in clinical trials for myeloma. These findings are pre-clinical, meaning the next step would be studies in patients to determine whether the results translate.
"Impact of frailty tools on outcomes in myeloma: MRP and simplified index predict survival but differ in infection risk stratification"
Source
Zhang, S., Li, L., Tian, W., Xiang, C., Zhu, Q., Wang, T., … Yao, Q. (2026). Impact of frailty tools on outcomes in myeloma: MRP and simplified index predict survival but differ in infection risk stratification. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2639783 March 9, 2026.
Overview
When doctors assess a newly diagnosed myeloma patient, knowing how physically vulnerable that person is can be as important as knowing the cancer's stage. Frailty — a measure of overall health reserve — affects how well patients tolerate treatment and how long they are likely to live. This study compared two frailty scoring tools to see how well each predicted survival and serious infections in 205 myeloma patients treated at a single hospital between July 2014 and July 2022.
The two tools were the UK Myeloma Alliance Risk Stratification (MRP) and the Simplified Frailty Index (FI). Both classify patients as frail or non-frail based on factors such as age, functional status, and other health conditions.
Patients classified as frail by either tool lived considerably shorter lives than those classified as non-frail. Median overall survival was 36 months in frail patients versus 75 months in non-frail patients by MRP, and 38 months versus 76 months by FI.
Progression-free survival — the time before the disease worsened — followed the same pattern: 11 months in frail patients versus 21 to 23 months in non-frail patients, depending on the tool. One-year mortality was also higher in frail patients under both systems.
For predicting serious infections in the first months of treatment, the two tools diverged. The Simplified FI predicted early severe infections (P = 0.012), while MRP did not reach statistical significance (P = 0.237). Neither tool outperformed the other by a statistically meaningful margin on this measure.
Patients flagged as frail by both tools simultaneously had the worst outcomes, though the difference between that group and those flagged by only one tool was not statistically significant.
"A multicenter retrospective study of plasma d‑dimer levels for evaluating treatment response in multiple myeloma"
Source
Wu, A., Zuo, W., Gao, B. et al. A multicenter retrospective study of plasma d‑dimer levels for evaluating treatment response in multiple myeloma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41696-9 March 9, 2026.
Overview
D-dimer is a protein fragment released into the blood when clots break down. It is already used in hospitals to detect blood clots, but this study examined whether tracking D-dimer levels before and after chemotherapy could also indicate how well myeloma treatment is working.
Researchers enrolled 160 newly diagnosed myeloma patients across multiple hospitals and measured D-dimer levels at diagnosis and again after eight cycles of chemotherapy. They then compared those changes against each patient's treatment response, which was classified as complete response, partial response, stable disease, or progressive disease.
At diagnosis, D-dimer levels were similar across all four groups — there was no meaningful difference between patients who would later respond well and those who would not.
After eight cycles of chemotherapy, the picture changed. Patients whose myeloma responded — either completely or partially — showed substantial drops in D-dimer: a median reduction of 45% in the complete response group and 39% in the partial response group. Patients whose disease progressed showed the opposite: D-dimer rose by a median of 19%. The difference between responders and non-responders was statistically significant (p < 0.001).
The findings suggest that tracking how D-dimer changes during treatment, rather than measuring it at a single point, may give doctors additional information about whether chemotherapy is working. D-dimer testing is inexpensive and widely available, which would make it practical to add to routine monitoring if larger studies confirm these results.
"Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy"
Source
Wang Z, Wang G, Liu Y, Zhao Y, Guo S, Yang Y, et al. Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy. Journal for ImmunoTherapy of Cancer. 2026;14:e014040. https://doi.org/10.1136/jitc-2025-014040 March 9, 2026.
Overview
CAR-T therapy engineers a patient's own immune cells to recognize and kill cancer cells by targeting a specific protein on their surface. In multiple myeloma, one reason CAR-T therapy eventually fails is that myeloma cells reduce or eliminate the surface proteins the engineered cells are designed to attack — a process called antigen escape. Most research has focused on genetic explanations for this, where the gene encoding the target protein is mutated or silenced. This study identified a different mechanism, one that operates without any change to the underlying DNA.
Researchers found that a subset of myeloma cells produces high levels of a metabolic enzyme called RRM2. In these cells, RRM2 acts as a trafficking regulator — it diverts a pair of immune-recognition proteins called MICA and MICB away from the cell surface and into cellular compartments where they are broken down, while simultaneously blocking the recycling pathway that would return them to the surface. The result is that CAR-T cells targeting MICA/B find little to recognize on these myeloma cells.
The researchers identified this RRM2-high subpopulation using single-cell gene analysis and confirmed its presence in patient samples. They then tested whether blocking RRM2 could reverse the problem.
The drug they used was osalmid, an already-approved compound previously characterized as an RRM2 inhibitor. At doses below those that directly kill cells, osalmid restored MICA/B to the myeloma cell surface. When combined with CAR-T cells in laboratory organoid models and animal models, the combination produced more durable tumor control than CAR-T alone. The engineered T cells expanded more, produced more active cytokines, and showed less exhaustion over time.
The findings reframe antigen escape as a dynamic, reversible process in at least some myeloma cells, rather than a permanent genetic loss. Osalmid is already approved for clinical use, which shortens the path to testing this combination in patients. Whether the approach extends to CAR-T therapies targeting proteins other than MICA/B remains to be established in further studies.
"Trends in renal failure–related mortality among U.S. multiple myeloma patients aged ≥ 45 years, 1999–2023: analysis of CDC data"
Source
Jiang, Y., Meng, Z., Liang, G. et al. Trends in renal failure–related mortality among U.S. multiple myeloma patients aged ≥ 45 years, 1999–2023: analysis of CDC data. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43754-8 March 9, 2026.
Overview
CAR-T therapy engineers a patient's own immune cells to recognize and kill cancer cells by targeting a specific protein on their sKidney failure is one of the most serious complications of multiple myeloma, affecting a substantial portion of patients and worsening survival. Researchers examined 24 years of U.S. death certificate data — from 1999 to 2023 — to track how mortality in myeloma patients with kidney failure as a contributing cause of death has changed over time, and whether that change has been equal across different groups.
The data came from the CDC WONDER database, which compiles national death records. The analysis included adults aged 45 and older whose death certificates listed myeloma as the underlying cause and kidney failure as a contributing cause.
Overall, age-adjusted mortality from this combination fell over the study period, dropping from 2.39 to 1.60 deaths per 100,000 people — a decline of about 1.3% per year on average. That trend held across most age groups.
The decline was not evenly distributed. Men died at higher rates than women throughout the entire period. Non-Hispanic Black patients had the highest mortality rates of any racial or ethnic group. People living outside major metropolitan areas and those in the Midwest had persistently higher rates than their counterparts elsewhere. Among adults 85 and older, mortality stopped declining in recent years and showed a modest increase.
The findings identify which groups have benefited least from treatment advances over the past two decades. Older adults, Black patients, rural residents, and people in the Midwest represent populations where targeted efforts to prevent and treat myeloma-related kidney failure are most needed.
"Theranostic Potential of [177Lu]Lu-DOTA-Tocilizumab in Multiple Myeloma: A Preclinical Evaluation"
Source
Camacho X, Cabrera M, Perroni C, Tassano M, Fernández M, Oddone N, Riva E, Gambini JP, Cabral P. Theranostic Potential of [177Lu]Lu-DOTA-Tocilizumab in Multiple Myeloma: A Preclinical Evaluation. Anticancer Agents Med Chem. 2026 Mar 10. doi: 10.2174/0118715206406408251125050709. Epub ahead of print.
Overview
Myeloma cells depend partly on a signaling protein called IL-6 to grow and spread. Tocilizumab is an antibody drug that blocks the receptor IL-6 binds to, and it is already approved for other conditions. Researchers tested whether tocilizumab could be converted into a theranostic agent — a compound that both delivers radiation directly to cancer cells and makes those cells visible on imaging scans — by attaching a radioactive element called lutetium-177.
To do this, the researchers chemically modified tocilizumab to carry a molecular cage called DOTA, which holds the lutetium-177 in place. They then tested the resulting compound, [177Lu]Lu-DOTA-Tocilizumab, in lab conditions and in mice carrying myeloma tumors.
In lab tests, the compound remained chemically stable and retained its ability to bind IL-6 receptors. About 84% of the labeled antibody remained active and capable of recognizing its target — a measure called immunoreactive fraction.
In mice, the compound accumulated in myeloma tumors at substantially higher concentrations than in surrounding muscle tissue. At 24 hours after injection, the tumor-to-muscle ratio was 11.7; at 48 hours it was 9.5, indicating the compound stayed preferentially in tumor tissue over time rather than dispersing broadly.
The results establish that lutetium-177-labeled tocilizumab can be synthesized stably, reaches myeloma tumors selectively in animal models, and retains its receptor-binding function after modification. The compound has not yet been tested in humans. Further studies are needed to assess dosing, safety, and whether the tumor uptake observed in mice translates to patients.
"Toward a cure for multiple myeloma within a decade"
Source
Mohty, M., Malard, F., Facon, T. et al. Toward a cure for multiple myeloma within a decade. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01461-7 March 10, 2026.
Overview
Multiple myeloma has long been considered treatable but not curable. That assumption is being tested by a generation of treatments that are producing deeper and longer remissions than were achievable a decade ago. This review examined where the field stands and what would need to happen for cure to become a realistic outcome for some patients.
The authors argue that the best opportunity for cure lies at diagnosis, before the cancer has had time to diversify genetically and before the immune system has been compromised by years of disease. A stage called smoldering myeloma — where the cancer is present but not yet causing symptoms — may offer a window for early intervention. Several trials have shown that treating high-risk smoldering myeloma with targeted antibody therapies can delay progression to active disease, and some have shown a survival benefit.
A central concept in the review is minimal residual disease, or MRD — a measure of how many myeloma cells remain after treatment, detectable down to one cell in a million. Sustained MRD negativity, meaning no detectable disease for an extended period, is increasingly used as a proxy for long-term disease control. The authors propose that two years of sustained MRD negativity may be sufficient for standard-risk patients, while high-risk patients may need three or more years before treatment can be stopped. Five years off therapy without relapse, they suggest, may be close enough to cure to be treated as such clinically.
Reaching that depth of response requires combining multiple drug classes — typically four agents used together in induction, followed by consolidation and maintenance — and tailoring the approach to each patient's risk profile.
The review identifies several obstacles. MRD testing methods are not yet standardized across centers. Clinical trials have not consistently used MRD negativity as the primary endpoint, making it harder to compare results. Treatment toxicity and quality of life remain concerns, particularly for patients who may be on therapy for years. Access to the newest treatment combinations is uneven globally.
"High body-mass index and multiple myeloma risk: insights from the global burden of disease 2021 study and identification of core target genes"
Source
Zhou, L., Zhang, Y., & Li, J. (2026). High body-mass index and multiple myeloma risk: insights from the global burden of disease 2021 study and identification of core target genes. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2641929 March 10, 2026.
Overview
Higher body weight is an established risk factor for several cancers, and its relationship to multiple myeloma has been drawing increasing attention. This study used data from the Global Burden of Disease 2021 study to measure how much of the global myeloma death toll is attributable to high body mass index (BMI), and combined that with a gene-level analysis to identify biological targets that may link the two.
In 2021, an estimated 9,165 myeloma deaths worldwide were attributed to high BMI — a 203% increase from 1990. The age-standardized mortality rate rose from 0.08 to 0.11 deaths per 100,000 people over that period, and the measure of years of healthy life lost followed a similar trajectory. Men and older adults carried a disproportionate share of that burden. Projections suggest the death toll in this group will continue rising over the next 25 years.
The researchers also analyzed gene expression data to look for biological mechanisms that might explain the BMI-myeloma link. Two genes emerged as candidates: SLC25A13, which is involved in cellular metabolism, and THOC2, which plays a role in how genetic information is processed inside cells. Both appeared connected to pathways related to immune function, cell growth, and metabolism in myeloma.
The gene findings are preliminary. Identifying a candidate target in a bioinformatic analysis is an early step; whether blocking or modifying SLC25A13 or THOC2 affects myeloma in patients would require laboratory and clinical validation.
"Real World Outcomes of Multiple Myeloma Patients that Reach Third Line Therapy: A Canadian Report"
Source
Martha Louzada, Donna Reece, Christopher P. Venner, Darrell White, Jiandong Su, Michael P. Chu, Victor H. Jimenez- Zepeda, Arleigh Mccurdy, Kevin Song, Hira Mian, Michael Sebag, Debra Bergstrom, Julie Stakiw, Anthony Reiman, Rami Kotb, Muhammad Aslam, Rayan Kaedbey, Engin Gul, Smriti Sharma, Richard LeBlanc, Real World Outcomes of Multiple Myeloma Patients that Reach Third Line Therapy: A Canadian Report, Blood Neoplasia, 2026, 100215, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2026.100215. March 10, 2026.
Overview
When myeloma returns after two prior lines of treatment, the choice of what to try next depends on which drugs a patient has already received, how their disease responded, and how healthy they are overall. This study used data from the Canadian Myeloma Research Group database — which holds records on more than 10,000 Canadians with plasma cell disorders — to examine what third-line treatments were used between 2015 and 2020 and how patients did on each.
The analysis included 1,125 patients. The most commonly used drug classes were immunomodulatory agents, used in 62% of patients; proteasome inhibitors, used in 44%; and anti-CD38 antibodies such as daratumumab, used in 25%.
Outcomes varied considerably by regimen. The combination of daratumumab with lenalidomide, with or without a steroid, produced the longest median progression-free survival at 25.6 months. Regimens combining an anti-CD38 antibody with pomalidomide, and other proteasome inhibitor-based combinations, had median progression-free survival between 6 and 9 months. Median overall survival across the full cohort was 29.7 months.
Several factors predicted worse outcomes: high-risk genetic abnormalities on FISH testing, a short interval between diagnosis and needing third-line treatment, prior exposure to three drug classes, prior proteasome inhibitor use, and resistance to lenalidomide.
The findings reflect real-world prescribing patterns rather than controlled trial conditions, which means patient selection and access to specific drugs influenced the results. The data offer a benchmark for what outcomes currently look like in third-line myeloma outside of clinical trials in Canada.
"Autologous Hematopoietic Cell Transplantation (AHCT) for the Treatment of Newly Diagnosed Multiple Myeloma"
Source
Zhubin Gahvari, Natalie S. Callander, Autologous Hematopoietic Cell Transplantation (AHCT) for the Treatment of Newly Diagnosed Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.005. March 10, 2026.
Overview
For 25 years, autologous stem cell transplant — a procedure in which a patient's own stem cells are collected, stored, and reinfused after high-dose chemotherapy — has been a standard part of initial treatment for younger, fitter myeloma patients. The rationale was straightforward: transplant deepened responses beyond what drug therapy alone could achieve.
That rationale is now being tested. Newer drug combinations, including quadruplet regimens and T cell-redirecting therapies, produce high rates of deep remission and, in some patients, no detectable disease by the most sensitive available tests. Whether transplant adds meaningful benefit on top of those responses is no longer obvious.
This review traced the history of transplant in myeloma and examined the most recent phase III trials that included transplant as part of initial treatment, with the aim of separating transplant's contribution to outcomes from the effect of the drug regimens surrounding it. It also summarized ongoing trials directly comparing transplant against drug-only approaches — both chemotherapy-based combinations and regimens built around T cell-redirecting agents such as bispecific antibodies or CAR-T therapy.
The central question the review addresses is whether transplant remains necessary when the drugs available before and after it are substantially more effective than they were when transplant became standard practice.
"Quadruplet daratumumab in combination with bortezomib, lenalidomide, and dexamethasone as front-line regimen improved clinical outcomes in high-risk myeloma patients in China: a multi-centered prospective real-world study"
Source
Cheng, L., Liang, D., Jia, J. et al. Quadruplet daratumumab in combination with bortezomib, lenalidomide, and dexamethasone as front-line regimen improved clinical outcomes in high-risk myeloma patients in China: a multi-centered prospective real-world study. BMC Cancer (2026). https://doi.org/10.1186/s12885-026-15815-8 March 10, 2026.
Overview
Standard initial treatment for multiple myeloma in many centers combines three drugs: bortezomib, lenalidomide, and dexamethasone, known as VRd. Adding a fourth drug, the anti-CD38 antibody daratumumab, to make D-VRd has shown stronger responses in clinical trials. This study examined how the two regimens compared in routine clinical practice across six hospitals in China, with particular attention to patients whose myeloma carries high-risk genetic features.
The study enrolled 100 newly diagnosed patients treated with D-VRd between 2020 and 2024, and compared them to 221 patients treated with VRd from an earlier period. Because the groups were treated at different times, follow-up was longer in the VRd group (40 months versus 16 months), which limits direct comparison of longer-term outcomes.
At one year, 92% of patients on D-VRd had not progressed, compared to 84.5% on VRd. One-year overall survival was 99% versus 97%. Both differences were statistically significant.
The benefit was more pronounced in patients with high-risk genetic abnormalities. Among those with at least one high-risk chromosomal change, one-year progression-free survival was 91.5% with D-VRd versus 80% with VRd. In patients with two or more high-risk features — the highest-risk group — one-year progression-free survival was 95% versus 72%. Patients with specific abnormalities, including deletion of chromosome 17p and extra copies of chromosome 1q, also showed meaningful improvements with D-VRd.
The safety profiles differed in two respects: low white blood cell counts were more common with D-VRd (23% versus 7%), while peripheral neuropathy — nerve pain and numbness — was less common (17% versus 33%).
The findings add real-world data supporting D-VRd over VRd as initial treatment, particularly for high-risk patients, though the non-randomized design and difference in follow-up length mean the survival comparisons should be interpreted with caution.
"Precision medicine in myeloma demands precision imaging: is whole body MRI the solution?"
Source
Messiou, C., Kaiser, M. Precision medicine in myeloma demands precision imaging: is whole body MRI the solution?. Cancer Imaging 26, 37 (2026). https://doi.org/10.1186/s40644-026-01017-9 March 11, 2026.
Overview
Myeloma treatment has improved substantially over the past two decades, with median survival more than doubling in many patient groups. As patients live longer with the disease, the tools used to monitor it need to keep pace. This review examined the evidence for whole-body MRI (WB-MRI) in myeloma, what current guidelines recommend, and where the technology is heading.
Traditional bone imaging in myeloma used X-rays or CT scans to detect holes in bone caused by the cancer. By the time those holes appear, irreversible damage has already occurred. MRI images the bone marrow directly, detecting disease before bone destruction begins. The International Myeloma Working Group updated its diagnostic criteria to include a positive MRI — defined as one or more lesions larger than 5mm — as sufficient evidence to start treatment, even without bone damage on other scans.
A standardized whole-body MRI protocol called MY-RADS was developed to ensure consistent imaging across centers. It covers the skull to the upper thighs using a combination of sequences that detect both individual lesions and more diffuse disease spread throughout the marrow.
In the UK, national guidance from NICE recommends WB-MRI as the first imaging test for all patients with suspected myeloma. Adoption has grown from 27% of centers in 2018 to 69% in 2024. In the US, insurance and reimbursement barriers have slowed uptake, though a number of centers have negotiated pre-authorizations and are using it routinely.
Beyond diagnosis, WB-MRI is playing a growing role in smoldering myeloma — a precursor state where the cancer is present but not yet causing symptoms. In some patients, WB-MRI finds lesions that blood and marrow tests miss, reclassifying them as having active disease that warrants treatment. In others, a normal scan provides evidence that watchful waiting is safe.
WB-MRI also adds information in patients assessed for minimal residual disease. Patients with residual disease visible on WB-MRI have shorter progression-free and overall survival even when marrow sampling shows no detectable cells, because myeloma is unevenly distributed and a single marrow biopsy can miss disease present elsewhere.
Several developments are likely to expand WB-MRI's role. Faster scanning protocols are reducing the time patients spend in the scanner. AI tools are being developed to automate image reading, which could reduce the radiologist time required and make results more consistent. Quantitative measurements — including the total volume of diseased marrow and the water content of lesions — are being validated as objective markers of treatment response that could eventually be incorporated into standard response criteria. Trials comparing WB-MRI directly with PET/CT are ongoing, and hybrid PET/MRI scanners that combine both modalities are being evaluated.
The main barriers to wider use are scanner availability, the need for trained radiologists, and reimbursement structures that do not yet reflect the clinical value of the technique in many health systems.
"Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed Refractory Multiple Myeloma"
Source
Rintu Sharma, Andree-Anne Pelland, Katherine Lajkosz, Esther Masih-Khan, Harjot Singh. Vohra, Sita Bhella, Christine I. Chen, Vishal Kukreti, A. Keith Stewart, Suzanne Trudel, Chloe Yang, Donna E. Reece, Chris Venner, Guido Lancman; Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed Refractory Multiple Myeloma. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-25-0372 March 11, 2026.
Overview
Teclistamab is a bispecific antibody that redirects immune cells to kill myeloma cells. It produces responses in most patients, but 30 to 40% do not respond to initial treatment. This study identified clinical features that predict non-response and tested whether chemotherapy given before teclistamab could improve outcomes in those patients.
Researchers analyzed data from 90 patients across two independent cohorts. They identified four features associated with poor response: disease that had spread outside the bone marrow, plasma cell leukemia (myeloma cells circulating in the blood), myeloma cells making up 50% or more of the bone marrow, and a blood transfusion within the prior 30 days. Patients with any of these features were classified as having high-intensity myeloma, or Hi-MM.
The difference in outcomes between the two groups was large. Patients without Hi-MM had overall response rates of 84 to 96%. Those with Hi-MM responded at rates of only 20 to 40%, with significantly shorter progression-free and overall survival.
The researchers then tested whether reducing disease burden with chemotherapy before starting teclistamab could change outcomes for Hi-MM patients. Among 19 patients who received debulking chemotherapy first, 79% subsequently responded to teclistamab. All patients who no longer met Hi-MM criteria after chemotherapy responded. Four patients had previously failed a different BCMA-targeting bispecific antibody immediately before debulking; all four achieved deep responses to teclistamab afterward.
The findings suggest that a small set of readily available clinical measurements can identify patients unlikely to respond to teclistamab, and that reducing disease burden first may convert non-responders into responders.
"Dynamic biomarker-based machine learning model predicts short-term treatment response in multiple myeloma"
Source
Xiong, Y., Xu, J., Li, B. et al. Dynamic biomarker-based machine learning model predicts short-term treatment response in multiple myeloma. J Transl Med (2026). https://doi.org/10.1186/s12967-026-07946-0 March 11, 2026.
Overview
Standard myeloma staging systems — including the ISS and R-ISS — use measurements taken at diagnosis to estimate prognosis. They do not update as treatment proceeds, which limits their ability to flag patients whose disease is not responding until progression becomes clinically obvious. This study tested whether immune and tumor markers measured repeatedly during treatment could predict short-term outcomes more accurately.
Researchers analyzed data from 662 newly diagnosed myeloma patients treated between 2017 and 2021. At baseline and every two treatment cycles up to cycle 10, they measured three categories of markers: lymphocyte subsets in the blood (including CD8+ T cells and CD56+ natural killer cells), cytokine levels, and the surface characteristics of myeloma cells in the bone marrow. They used these measurements to train a machine learning model and compared its predictive accuracy against conventional staging systems.
Standard staging performed poorly at predicting short-term treatment response beyond cycle 2. The biomarker-based model outperformed it at every measured cycle. At cycle 4, the model achieved an F1 score — a combined measure of precision and completeness — of 0.75, compared to 0.32 for R-ISS. The model's performance held up whether all measured biomarkers were included or a reduced set of the most informative ones was used.
The practical implication is timing. If a model can identify patients whose treatment is unlikely to produce an adequate response by cycle 2, doctors have the opportunity to intensify treatment or switch regimens before the disease has progressed further. Whether acting on those early predictions improves long-term survival would need to be tested in a prospective trial.
"The role of KPNA3 in multiple myeloma: implications for targeting nuclear import"
Source
Luo, H., Mi, Z., Huang, J. et al. The role of KPNA3 in multiple myeloma: implications for targeting nuclear import. Apoptosis 31, 98 (2026). https://doi.org/10.1007/s10495-026-02292-4 March 11, 2026.
Overview
Cells constantly shuttle proteins and other molecules between the cytoplasm and the nucleus, a process controlled in part by a family of transport proteins called importins. This study examined one member of that family, KPNA3, in myeloma.
The researchers found that KPNA3 is expressed at high levels in myeloma cells, and that patients with higher KPNA3 expression had worse outcomes than those with lower levels. When they reduced KPNA3 activity in myeloma cells — in both cell culture and animal models — the cells divided more slowly, died at higher rates, and became more sensitive to existing drugs. Tracing the mechanism, the researchers found that reducing KPNA3 suppressed a gene called ALDH2 and reduced activity in the hedgehog signaling pathway, both of which support myeloma cell survival.
The researchers then identified ivermectin — an antiparasitic drug already approved for human use — as a compound that binds directly to KPNA3. In myeloma cells, ivermectin reduced KPNA3 protein levels and triggered cell death. When combined with selinexor, a drug that targets a related nuclear transport protein already approved for myeloma, the two drugs produced a synergistic effect in both cell and animal models, meaning the combination was more effective than either drug alone.
The findings identify KPNA3 as a functional contributor to myeloma cell survival and suggest that disrupting nuclear transport — either through ivermectin, selinexor, or their combination — warrants further investigation as a treatment approach. This work was conducted in cell and animal models; clinical testing in patients has not yet been done.
"Quantifying the contribution of modifiable risk factors for progression of MGUS to multiple myeloma in a Veteran population"
Source
Wang M, Sigel B, Liu L, et al. Quantifying the contribution of modifiable risk factors for progression of MGUS to multiple myeloma in a Veteran population. Int J Cancer. 2026;1-11. doi:10.1002/ijc.70412 March 11, 2026.
Overview
Multiple myeloma is almost always preceded by a condition called MGUS (monoclonal gammopathy of undetermined significance), in which abnormal proteins appear in the blood but have not yet caused disease. Most people with MGUS never develop myeloma, but some do — and identifying which risk factors drive that progression could point toward prevention strategies.
Researchers analyzed data from 35,073 veterans with MGUS in the Veterans Health Administration. Veterans were chosen as a study population because they have higher rates of several myeloma risk factors than the general population, including older age, higher proportions of men, and potential past exposure to Agent Orange.
The study calculated how much of the progression burden in this population could be statistically attributed to each known risk factor, after accounting for the others and for the competing risk of death from other causes.
Excess body weight — defined as a BMI of 25 or higher — was the largest contributor across all groups. An estimated 27% of MGUS progressions in the cohort were attributable to excess BMI, and that figure was consistent across Black veterans (27.1%), White veterans (27.2%), and the full cohort. No other evaluated risk factor came close.
The finding is relevant because BMI is modifiable — unlike age, sex, or race, which were also examined. The authors suggest that weight management interventions in people already diagnosed with MGUS could reduce their risk of progressing to active myeloma, though a prospective trial would be needed to determine whether weight loss actually lowers progression rates rather than simply correlating with them.
"Positioning of Melflufen in Heavily Pretreated RRMM Patients: Real-World Evidence in a Rapidly Evolving Therapeutic Landscape"
Source
K.Mancuso, S.Masci, M.Talarico, et al., “Positioning of Melflufen in Heavily Pretreated RRMM Patients: Real-World Evidence in a Rapidly Evolving Therapeutic Landscape,” European Journal of Haematology (2026): 1–9, https://doi.org/10.1111/ejh.70156. March 11, 2026.
Overview
When myeloma has stopped responding to three or more prior treatment classes, options become limited. Melflufen, a chemotherapy drug that concentrates inside cells before releasing an active form of melphalan, was approved in Europe combined with dexamethasone for patients in exactly this situation. Real-world data on how it performs outside clinical trials remain sparse.
Researchers at a single center in Bologna, Italy, treated 17 patients with relapsed or refractory myeloma with melflufen-dexamethasone between December 2021 and July 2025. All had received multiple prior therapies and were treated outside of a clinical trial.
41% of patients responded to treatment. Among those who responded, median progression-free survival was 9 months. In the full cohort it was 3.7 months. Median overall survival had not been reached at the time of analysis.
Blood count toxicities were common: neutropenia and thrombocytopenia each occurred in 53% of patients at grade 3 or higher, and anemia in 35%. Serious non-blood toxicities were less frequent — infections in 23.5% and fatigue in 6%. No secondary cancers were recorded.
Eleven of the 17 patients went on to receive further treatment after melflufen, including seven who received newer immunotherapies such as bispecific antibodies or CAR-T. Those who subsequently received immunotherapy achieved deeper and more durable responses than those who received conventional regimens, suggesting melflufen did not compromise the effectiveness of later T cell-redirecting treatments.
The cohort was small and the follow-up short, and patients were older and more heavily pretreated than those enrolled in the trials that supported approval. The results should be interpreted accordingly.
"Real-World Treatment Patterns of Elranatamab in Patients with Multiple Myeloma in Japan: The EVEREST Study. ClinicoEconomics and Outcomes Research"
Source
Yoshihara, S., Meche, A., Hlavacek, P., Johnson, S. M., Demers, A. S., Nador, G., … Chen, Y. (2026). Real-World Treatment Patterns of Elranatamab in Patients with Multiple Myeloma in Japan: The EVEREST Study. ClinicoEconomics and Outcomes Research, 18. https://doi.org/10.2147/CEOR.S581258 March 11, 2026.
Overview
Elranatamab is a bispecific antibody that targets BCMA on myeloma cells and CD3 on T cells, redirecting the immune system to kill the cancer. It was approved in Japan in March 2024 for relapsed or refractory myeloma. This study examined how the drug has been administered in routine practice using claims data from a large Japanese hospital database.
The analysis included 253 patients who started elranatamab between March 2024 and March 2025. Median age was 74 years. Median treatment duration was 60 days, though this varied considerably — the middle 50% of patients were treated for between 26 and 136 days.
Elranatamab is given in three phases: an initial step-up period using lower doses to reduce the risk of cytokine release syndrome, followed by weekly dosing, then every-two-weeks dosing. During the step-up phase, dosing intervals closely matched the approved schedule. During the weekly maintenance phase, some patients received doses less frequently than recommended — the mean interval between doses was 9.8 days rather than 7. During the every-two-weeks phase, dosing was closer to the label.
Almost all step-up doses were given in inpatient settings. Most maintenance doses were given in outpatient settings.
Projected annual vial usage was 34.4 per patient, compared to 39.0 per patient implied by the full label schedule — a difference driven by the less frequent dosing seen during the weekly maintenance period.
The study describes administrative patterns rather than clinical outcomes, so it cannot address whether the dosing variations observed affected response rates or survival.
"PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma"
Source
Liu, Y., Yan, S., Shu, X., Xu, Q., Zhang, M., Wang, Y., … Guo, T. (2026). PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma. Annals of Medicine, 58(1). https://doi.org/10.1080/07853890.2026.2639658 March 11, 2026.
Overview
Myeloma cells rely heavily on mitochondria — the energy-producing structures inside cells — to fuel their growth. This study examined a protein called PPRC1, which helps regulate mitochondrial activity, and asked whether it plays a functional role in myeloma and whether its levels in tumor cells correlate with patient outcomes.
Researchers analyzed PPRC1 expression using data from public myeloma databases and an independent patient cohort. PPRC1 was expressed at higher levels in myeloma cells than in normal plasma cells, and patients with higher PPRC1 expression had shorter overall survival. In multivariate analysis — which accounts for other known prognostic factors — PPRC1 remained an independent predictor of worse outcomes. Adding PPRC1 to the standard R-ISS staging system improved survival prediction beyond what R-ISS alone provided.
Gene pathway analysis showed that PPRC1 expression correlated with activity in oxidative phosphorylation — the process by which mitochondria generate energy — and in several cancer-promoting signaling pathways. An association between PPRC1 levels and immune cell infiltration in the tumor environment was also observed, though the functional significance of that relationship was not fully characterized.
When the researchers silenced PPRC1 in myeloma cell lines using siRNA, the cells divided more slowly, underwent cell cycle arrest, died at higher rates, and showed reduced mitochondrial energy production.
The findings identify PPRC1 as a regulator of myeloma cell metabolism and a candidate therapeutic target. The work was conducted in cell lines and patient databases; whether blocking PPRC1 is feasible or effective in patients remains to be tested.
"Carfilzomib, lenalidomide, and dexamethasone compared with lenalidomide treatment after autologous haematopoietic stem-cell transplantation in patients with multiple myeloma (ATLAS): primary analysis of a randomised, open-label, phase 3 trial"
Source
Dytfeld, Dominik et al. Carfilzomib, lenalidomide, and dexamethasone compared with lenalidomide treatment after autologous haematopoietic stem-cell transplantation in patients with multiple myeloma (ATLAS): primary analysis of a randomised, open-label, phase 3 trial. The Lancet Haematology, Volume 0, Issue 0 March 11, 2026.
Overview
After a stem cell transplant for myeloma, patients typically receive maintenance therapy — ongoing treatment at lower doses designed to keep the disease from returning. Lenalidomide taken daily has been the standard approach. The ATLAS trial tested whether adding carfilzomib and dexamethasone to lenalidomide for the first several cycles after transplant would produce better outcomes than lenalidomide alone.
The trial enrolled 180 patients at 12 centers in the US and Poland between 2016 and 2020. Patients were randomly assigned to receive either the three-drug combination (carfilzomib, lenalidomide, and dexamethasone) or lenalidomide alone. Patients in the three-drug group who had standard-risk genetics and no detectable residual disease after six cycles were switched to lenalidomide alone after cycle 8 — a de-escalation approach based on response.
At a median follow-up of 69 months, the difference in progression-free survival was substantial. Four-year progression-free survival was 67.5% in the three-drug group versus 38% in the lenalidomide group. Median progression-free survival was 72.8 months with the combination versus 37.3 months with lenalidomide alone — a hazard ratio of 0.46, meaning patients on the three-drug regimen had roughly half the risk of progression or death at any given time point.
Serious adverse events occurred in 30% of patients on the combination and 23% on lenalidomide alone. Neutropenia was the most common severe side effect in both groups, occurring in 48% of the combination group and 59% of the lenalidomide group. Thrombocytopenia was more common with the combination (13% versus 6%). Four deaths — two in each group — were considered possibly related to treatment.
The results support intensified maintenance for myeloma patients after transplant, with the option to de-escalate in lower-risk patients who achieve deep responses early.
"Characterization of Hypogammaglobulinemia, Infection Incidence, and Mortality in Patients Receiving B-cell Maturation Antigen Chimeric Antigen Receptor (CAR) T-cell Therapy"
Source
Liu, Katherine J. et al. Characterization of Hypogammaglobulinemia, Infection Incidence, and Mortality in Patients Receiving B-cell Maturation Antigen Chimeric Antigen Receptor (CAR) T-cell Therapy. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 0, Issue 0 March 11, 2026.
Overview
BCMA-targeted CAR-T therapy has produced strong responses in relapsed and refractory myeloma, but it can damage the immune system's ability to produce antibodies. This study examined how often patients developed low immunoglobulin G (IgG) levels — a condition called hypogammaglobulinemia — after CAR-T therapy, how long it persisted, and whether it affected infection rates and survival.
Researchers reviewed records from 147 myeloma patients who received BCMA CAR-T at a single large health system. Mean age was 65 years; 57% were male.
Low IgG was already common before treatment: 69% of patients had some degree of hypogammaglobulinemia before CAR-T, and 55% had moderate or severe deficiency. After CAR-T, those figures rose to 80% and 68% respectively. Severe deficiency — IgG at or below 200 mg/dL — was the most common category after treatment, affecting 42% of patients.
The problem persisted. Moderate to severe low IgG was present within the first three months after CAR-T in 62% of patients and remained at 12 months or beyond in 68%.
30% of patients developed a severe infection in the year following treatment, and 25% were hospitalized for infection. Patients who had low IgG before CAR-T were more than twice as likely to develop infections afterward. Lower post-CAR-T IgG levels and larger drops in IgG from baseline were both associated with higher mortality risk.
The findings suggest that monitoring IgG levels before and after CAR-T therapy, and considering immunoglobulin replacement for patients with significant deficiency, may be warranted — though prospective data on whether replacement reduces infections or improves survival in this population are still needed.
"Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape"
Source
Gay F, Buda G, Petrucci MT, Bolli N, Cea M, Derudas D, Mangiacavalli S, Montefusco V, Antonioli E, Barilà G, Basso M, Bertazzoni P, Bertuglia G, Bianco R, Carlisi M, Giudice MLD, Pepa RD, Fazio F, Franceschini L, Furlan A, Gozzetti A, Liberatore C, Mancuso K, Martino EA, Mele G, Monaco F, Morè S, Paris L, Pavan L, Pezzatti S, Rago A, Ribolla R, Roncato R, Rossini B, Sgherza N, Vassallo F, Vincelli DI, Za T, Musto P, Zamagni E. Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape. ESMO Open. 2026 Mar 11;11(3):106054. doi: 10.1016/j.esmoop.2025.106054. Epub ahead of print. .
Overview
Myeloma treatment has changed substantially over the past two decades, with newer drug combinations producing deeper remissions and longer survival than were achievable before. Despite that progress, patients with high-risk genetic features, kidney impairment, or early resistance to standard drugs continue to do poorly, and options for heavily pretreated patients remain limited.
Selinexor works by blocking a protein called XPO1, which normally shuttles tumor-suppressing proteins out of the cell nucleus. When XPO1 is inhibited, those proteins accumulate in the nucleus and can trigger myeloma cell death. It is taken orally, which distinguishes it from most other myeloma drugs given by infusion or injection.
Two selinexor-based regimens are currently approved for relapsed or refractory myeloma: selinexor combined with bortezomib and dexamethasone for patients with at least one prior line of therapy, and selinexor combined with dexamethasone alone for more heavily pretreated patients. Both have shown activity in subgroups that are difficult to treat with other approaches, including patients refractory to three drug classes, those with kidney dysfunction, those with high-risk chromosomal abnormalities, and those previously treated with anti-CD38 antibodies.
This review described selinexor's mechanism, its interactions with other drug classes, combinations under investigation, and its place in treatment sequencing. It also addressed practical management of toxicities — nausea, fatigue, and low platelet counts are the most common — and strategies to support treatment adherence.
As CAR-T therapy and bispecific antibodies have moved into earlier lines of treatment for some patients, selinexor's role has increasingly shifted toward patients who are ineligible for T cell-redirecting therapies or have exhausted them. Data on selinexor used before or after CAR-T, and in combination with bispecific antibodies, are being collected in ongoing trials but are not yet mature.
"Multiple Myeloma as a Second Primary Malignancy"
Source
Aathira, T.S., Mohan, V., Yadav, D.D. et al. Multiple Myeloma as a Second Primary Malignancy. Indian J Hematol Blood Transfus (2026). https://doi.org/10.1007/s12288-026-02361-3 March 11, 2026. .
Overview
As cancer treatments improve and patients survive their first malignancy for longer, a second, unrelated cancer diagnosed afterward is becoming more commonly recognized. This case series described eight patients who developed multiple myeloma after a prior cancer diagnosis at a single center between 2010 and 2024.
Median age at myeloma diagnosis was 68 years. The prior cancers included lymphoid malignancies in three patients, breast cancer in two, prostate cancer in one, tongue cancer in one, and a granulosa cell tumor in one. The median interval between the first cancer diagnosis and the myeloma diagnosis was four years, ranging from under one year to eleven years.
Most patients presented with symptomatic myeloma requiring treatment. IgG-kappa was the most common myeloma protein type, found in four of the eight patients. Six patients received systemic myeloma therapy, and four went on to autologous stem cell transplant. All four transplanted patients achieved sustained remission, with follow-up ranging from 47 to 123 months. Two patients died — one from respiratory failure related to H1N1 influenza, one while receiving supportive care only — and one was lost to follow-up.
The series is small and drawn from a single center, which limits generalizability. It does suggest, however, that standard myeloma treatment including transplant is feasible in patients whose prior cancer is in remission, and that durable responses are achievable in that setting.
"Risk of adverse events in elotuzumab-treated patients with multiple myeloma: a systematic review and meta-analysis"
Source
Zhaoyue Yan, Huali Dong, Yiping Du, Dapeng Li & Linlin Liu (2026) Risk of adverse events in elotuzumab-treated patients with multiple myeloma: a systematic review and meta-analysis, Annals of Medicine, 58:1, 2641930, DOI: 10.1080/07853890.2026.2641930 March 12, 2026.
Overview
Elotuzumab is a monoclonal antibody that targets a protein called SLAMF7 on myeloma cells and is used in combination with other drugs. This meta-analysis pooled safety data from six randomized controlled trials — 1,736 patients in total — to characterize which side effects occur more or less often with elotuzumab-containing regimens compared to control regimens.
Elotuzumab was associated with a lower rate of neutropenia (relative risk 0.86), which is notable given that neutropenia is one of the most common and serious side effects of myeloma treatment generally.
On the other side of the ledger, elotuzumab regimens were associated with higher rates of several adverse events. Overall infections were more frequent (relative risk 1.09), as were pneumonia (1.30), fever (1.47), and diarrhea (1.16). At grade 3 or 4 severity — the threshold where side effects typically require medical intervention or treatment modification — elotuzumab was associated with higher rates of severe lymphopenia (relative risk 1.86), severe pneumonia (1.57), severe diarrhea (1.47), severe infections (1.30), and cataracts (2.87).
The authors flag two important caveats for interpreting the cataract and metabolic findings. Elotuzumab trials tend to involve longer treatment durations and higher cumulative steroid exposure than control arms, and both cataracts and elevated blood sugar are known consequences of prolonged steroid use. Those findings may therefore reflect steroid exposure rather than elotuzumab itself.
No significant differences were found for anemia, thrombocytopenia, nausea, fatigue, rash, or several other commonly monitored side effects.
"MajesTEC-3: Redefining what’s possible in multiple myeloma"
Source
Al Hadidi S, Gaballa M. MajesTEC-3: Redefining what’s possible in multiple myeloma. Clinical Hematology International. 2026;8(1):56-59. doi:10.46989/001c.158751 March 12, 2026.
Overview
The MajesTEC-3 trial tested teclistamab, a bispecific antibody targeting BCMA, combined with daratumumab against standard daratumumab-based regimens in previously treated myeloma patients. At a median follow-up of 34.5 months, median progression-free survival had not been reached in the teclistamab-daratumumab group, compared to 18.1 months in the control arm. Three-year overall survival was 83% versus 65%. The PFS curves flattened after roughly six months, with more than 90% of patients still progression-free — a pattern that held out to three years.
Those numbers are comparable to outcomes reported with BCMA CAR-T therapy, but teclistamab is an off-the-shelf drug that does not require the weeks of manufacturing time that CAR-T demands.
The main safety concern was infection. Grade 3 or 4 infections occurred in 54% of patients, and 13 patients died from infection-related causes. Infection rates were highest in the first six months, before the trial added mandatory immunoglobulin replacement and antimicrobial prophylaxis to the protocol. After those amendments, infection rates fell. Cytokine release syndrome occurred but was grade 1 or 2 in all cases and resolved. Neurological toxicity occurred in 1% of patients.
One limitation in interpreting MajesTEC-3 is its trial population. Only 5% of enrolled patients had prior daratumumab exposure, and none were daratumumab-refractory. That profile is increasingly rare now that daratumumab-based four-drug regimens have become standard frontline treatment. A separate trial, MajesTEC-9, addressed this directly by enrolling patients who were predominantly refractory to anti-CD38 antibodies. In that population — 85% anti-CD38 refractory, 79% lenalidomide refractory — teclistamab monotherapy still reduced the risk of progression or death by 71% and death by 40% compared to standard of care. Together, the two trials establish teclistamab activity across both anti-CD38 sensitive and refractory populations.
Two questions now shape how the field will use these results. The first is treatment duration. Patients on bispecific antibodies currently receive them indefinitely, which sustains immunosuppression and cumulative infection risk. Fixed-duration approaches — stopping after 12 to 24 months in patients who achieve undetectable residual disease — are under investigation. A more individualized version of this would use MRD testing to guide when treatment stops, continuing in patients with persistent detectable disease and discontinuing in those who have sustained deep responses.
The second question is access. Unlike CAR-T, bispecific antibodies can in principle be given in community oncology settings rather than specialized centers. Realizing that potential requires training community oncologists in managing cytokine release syndrome and infections, building infrastructure for close monitoring, and addressing cost — these drugs are expensive, and cost-effectiveness data will be needed to support broader coverage.
Several trials are now testing teclistamab and similar bispecific antibodies earlier in the disease course, including in newly diagnosed patients and in combinations with other novel agents. Whether the outcomes seen in MajesTEC-3 hold in less heavily pretreated populations, and whether time-limited treatment can safely replace indefinite therapy, are the central questions those trials will need to answer.
"Sleep quality and sleepiness in adults with multiple myeloma. Is melatonin a potential treatment?"
Source
Fiori, M., de Azevedo, E. M., Rodrigues, L. S., Turt, K. S., Bruschi, D. P., & Lima, M. M. S. (2026). Sleep quality and sleepiness in adults with multiple myeloma. Is melatonin a potential treatment? Physiological Reports, 14, e70805. https://doi.org/10.14814/phy2.70805 March 12, 2026.
Overview
Poor sleep is a recognized problem in cancer patients, but it has not been well studied in myeloma specifically. This observational study measured sleep quality in 46 myeloma patients and 64 age-matched people without myeloma, and tested whether melatonin supplementation improved outcomes.
Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), a validated questionnaire covering seven components including how long it takes to fall asleep, total sleep duration, and whether sleep medications are needed. Daytime sleepiness was measured separately using the Epworth Sleepiness Scale.
yeloma patients had significantly worse overall sleep quality than controls. 75% of patients met criteria for poor sleep quality or a sleep disorder. Specific components that differed significantly between groups included time to fall asleep, total sleep duration, and reliance on sleep medications.
Daytime sleepiness scores did not differ between the two groups and were not affected by treatment — a finding the authors describe as a dissociation between nighttime sleep quality and daytime function.
The melatonin findings were unexpected. Supplementation did not improve overall sleep quality in myeloma patients, and in controls it was associated with worse PSQI scores. Melatonin affected some individual sleep parameters but not the overall score.
The study was small and observational, which limits what can be concluded about melatonin's role. The results suggest that sleep disturbance in myeloma is common enough to warrant routine assessment, but that melatonin alone is unlikely to be sufficient as a treatment. What approach would be effective remains an open question.
"Targeted MRIs inform clinical management in biochemically stable multiple myeloma patients presenting with new pain"
Source
Alina Denisa Dragan, Kevin Boyd, Erica Scurr, Dow-Mu Koh, Angela Riddell, Martin Kaiser, Christina Messiou, Targeted MRIs inform clinical management in biochemically stable multiple myeloma patients presenting with new pain, Clinical Radiology, 2026, 107309, ISSN 0009-9260, https://doi.org/10.1016/j.crad.2026.107309. March 13, 2026.
Overview
Myeloma can cause bone pain, but new pain does not always mean the disease is progressing — it can also result from degenerative changes, fractures unrelated to active disease, or other causes. When blood markers are stable, deciding whether to order a full whole-body MRI or a more limited scan of the painful area is a practical clinical question. This study examined whether a targeted MRI — covering only the region causing symptoms — could reliably guide management without the time and burden of whole-body imaging.
Researchers reviewed 134 targeted MRI scans performed over two years at a single center in 111 myeloma patients who had new pain but stable biochemical markers. Patients with known non-secretory disease or a second cancer were excluded.
The most common finding was degenerative change, present on 43% of scans. Fractures appeared on 39% of scans, but only one was related to progressive myeloma. 72% of scans showed no active disease. Among the 28% that did show active disease, 16% demonstrated new or growing lesions. Whole-body imaging was ordered as a follow-up in only 9% of cases.
Targeted MRI prompted a clinical intervention — a change in treatment or management — in 28 patients. Among 50 patients followed for a median of 26 months, no recurrence was identified on subsequent follow-up. The sensitivity of targeted MRI for detecting active disease was 96% and specificity was 90%.
The findings suggest that in myeloma patients with new pain and stable blood markers, a targeted scan of the affected area identifies active disease reliably and reduces the number of patients who need a full whole-body scan.
"Liposomal nanoparticles as a drug delivery system for improved treatment of multiple myeloma"
Source
Nemany A. N. Hanafy, Safacan Kolemen, Liposomal nanoparticles as a drug delivery system for improved treatment of multiple myeloma, RSC Advances, Volume 16, Issue 16, 2026, Pages 13995-14009, ISSN 2046-2069, https://doi.org/10.1039/d5ra09823h. March 13, 2026.
Overview
Standard myeloma chemotherapy distributes throughout the body, which limits how much drug can reach the tumor before side effects become unacceptable. Liposomes — tiny spherical particles made of the same lipid material as cell membranes — can carry drugs inside them and be engineered to release their contents preferentially at tumor sites. This review summarized recent research on liposomal drug delivery systems designed specifically for myeloma.
The bone marrow environment presents particular delivery challenges. Its vascular structure is complex, myeloma cells interact closely with surrounding stromal cells in ways that confer drug resistance, and some myeloma cells have stem-like properties that make them harder to kill. Liposomes can be modified with targeting molecules on their surface that bind to proteins expressed on myeloma cells, improving the proportion of drug that reaches the tumor rather than healthy tissue.
One practical advantage of liposomes is their ability to carry more than one drug simultaneously. Packaging two drugs with different mechanisms into a single particle allows them to arrive at the tumor together, which can produce effects greater than either drug alone and may help overcome resistance that develops when only one pathway is blocked.
A widely used modification — coating liposomes with polyethylene glycol (PEG) to extend their circulation time in the blood — introduces its own complication. The body can generate antibodies against PEG, which accelerates clearance of the particles on repeat dosing. Researchers have tested several approaches to reduce this immune response, including altering the shape and molecular weight of PEG chains and combining PEG variants of different sizes. Some liposomal formulations using these modifications have received FDA approval for clinical use in other cancers, establishing that the platform is viable in patients.
Work specific to myeloma remains largely in laboratory and early-stage development. The review identifies bone marrow targeting efficiency and managing immune responses to delivery vehicles as the two areas most in need of further work before liposomal approaches can move more broadly into myeloma clinical practice.
"Validation of the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) in patients with multiple myeloma who were enrolled in the CARTITUDE-4 trial"
Source
Mina, R., Mylin, A.K., Yokoyama, H. et al. Validation of the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) in patients with multiple myeloma who were enrolled in the CARTITUDE-4 trial. J Patient Rep Outcomes (2026). https://doi.org/10.1186/s41687-026-01034-z March 13, 2026.
Overview
Clinical trials increasingly include patient-reported outcome measures — questionnaires completed by patients themselves to capture how a disease and its treatment affect daily life. For those measures to be useful in regulatory submissions and treatment comparisons, they need to demonstrate reliability (producing consistent results under stable conditions) and validity (measuring what they claim to measure). This study assessed those properties for a myeloma-specific questionnaire called the MySIm-Q using data from the CARTITUDE-4 trial.
CARTITUDE-4 is a phase 3 trial comparing the CAR-T therapy ciltacabtagene autoleucel against standard regimens in 419 patients with lenalidomide-refractory myeloma who had received one to three prior lines of treatment. 361 of those patients completed MySIm-Q assessments, which cover two separate concepts: symptoms and their impact on daily functioning.
Internal consistency — the degree to which items within each scale measure the same underlying concept — met the predefined threshold for both the symptom score and the impact score. Test-retest reliability, which measures whether scores remain stable when a patient's condition has not changed, fell slightly below the threshold for both scores (0.67 and 0.65, against a target of 0.70).
The questionnaire performed well on validity assessments. Known-groups validity — the ability to distinguish between patients expected to differ in their scores based on disease characteristics — was established across multiple comparisons. Convergent validity (items correlating with related measures) and discriminant validity (items not correlating with unrelated measures) were supported at both the item and domain level.
The results support using the MySIm-Q as a patient-reported outcome instrument in myeloma trials, with the test-retest findings suggesting some caution in interpreting small score changes over short intervals as clinically meaningful.
"Optimal acquisition time of [68Ga]Ga-PentixaFor PET/CT for initial staging of multiple myeloma: an ancillary study to the PentiMyelo protocol"
Source
François, C., Carlier, T., Touzeau, C. et al. Optimal acquisition time of [68Ga]Ga-PentixaFor PET/CT for initial staging of multiple myeloma: an ancillary study to the PentiMyelo protocol. EJNMMI Res (2026). https://doi.org/10.1186/s13550-026-01410-2 March 13, 2026.
Overview
A PET tracer called [68Ga]Ga-PentixaFor targets a protein called CXCR4, which is expressed on myeloma cells, and is being investigated as an imaging tool to detect myeloma lesions throughout the body. One unresolved question is how long after injection the scan should be performed to produce the clearest images. This study tested several acquisition times to identify which produced the best contrast between tumor and background tissue.
Twenty myeloma patients were scanned at 60 minutes after injection — the time point being evaluated as a potential standard — plus additional scans at either earlier time points (30, 40, and 50 minutes) or later ones (75, 85, and 95 minutes). The researchers measured how much tracer accumulated in lesions relative to background tissue, and how much image noise was present at each time point.
Background uptake in the liver, spleen, and blood pool decreased over time, while image noise increased. Among the 343 lesions detected across both groups, scanning earlier or later than 60 minutes did not change whether a patient's scan was read as positive or negative — 10 of 20 patients had positive scans regardless of timing.
Where the time point mattered was image quality. In patients scanned at the earlier time points, tumor-to-background contrast was highest at 60 minutes. In patients scanned at the later time points, contrast remained stable across the 75 to 95 minute range without meaningful improvement over 60 minutes.
The results support 60 minutes post-injection as the standard acquisition time for this tracer, offering the best lesion contrast without the added noise that comes with longer delays.
"The influence of polymorphisms in cytokine genes on pain and response to palliative radiotherapy in multiple myeloma patients: prospective observational study"
Source
Rudzianskiene, Milda, Inciura, Arturas, Gerbutavicius, Rolandas, Rudzianskas, Viktoras, Ugenskiene, Rasa, Paukstaitiene, Renata, Dambrauskiene, Ruta, Vaitiekus, Domas, Kulboke, Migle and Juozaityte, Elona. "The influence of polymorphisms in cytokine genes on pain and response to palliative radiotherapy in multiple myeloma patients: prospective observational study" Scandinavian Journal of Pain, vol. 26, no. 1, 2026, pp. 20250013. https://doi.org/10.1515/sjpain-2025-0013 March 13, 2026.
Overview
Palliative radiotherapy is commonly used to relieve bone pain in cancer patients, but responses vary — some patients improve substantially while others do not. This study examined whether genetic differences in genes encoding inflammatory signaling proteins called cytokines could help explain that variation.
81 patients were enrolled. Pain severity and analgesic use were measured before radiotherapy and at 4, 12, and 24 weeks afterward. The researchers tested 12 genetic variants across six cytokine genes: IL-6, IL-10, TNF-α, IL-1α, IL-1β, and IL-1RA.
Two findings related to pain severity before treatment. Patients with a Karnofsky performance score of 60% or higher — a measure of functional ability — were less likely to have severe pain at baseline. Among genetic factors, patients carrying the GG variant of a specific IL-1RA gene polymorphism (IL1RN rs2234677) were more likely to have severe pain before radiotherapy began.
Three genetic variants were associated with treatment response. Patients carrying the CC variant of the IL-1α gene (IL1A rs1800587) had significantly better pain response to radiotherapy. The same pattern held for patients with the CC variant of the IL-1β gene (IL1B rs1143634). Patients with the CC variant of a second IL-1RA polymorphism (IL1RN rs315952) responded faster to radiation.
The study was small, which limits how confidently these associations can be generalized. If confirmed in larger cohorts, genetic variants in IL-1 pathway genes could potentially help identify which patients are most likely to benefit from palliative radiotherapy and at what pace.
"IDH2 Clonal Hematopoiesis and IKAROS Loss Cooperate in a B-ALL Subtype after Lenalidomide Therapy for Multiple Myeloma"
Source
Johanna M. Horns, Thomas Beder, Axel Künstner, Malwine Jeanette Barz, Sonja Bendig, Cecilia Bozzetti, Guranda Chitadze, Nikos Darzentas, Katharina Iben, Michaela Kotrova, José-Ignacio Martín-Subero, Mayukh Mondal, Martin Neumann, Raul Fernandez Perez, Aeint-Steffen Ströh, Wiebke Weßels, Lennart Lenk, Lars Velten, Boris Böll, Krischan Braitsch, Veit L. Bücklein, Johannes Duell, Christoph Faul, Walter Fiedler, Maher Hanoun, Snjezana Janjetovic, Felix Klingler, Stefan Knop, Christoph Röllig, Stefan Schwartz, Bernd M Spriewald, Björn Steffen, Klaus Wethmar, Hauke Busch, Nicola Gökbuget, Claudia D Baldus, Lorenz Bastian, Monika Brüggemann; IDH2 Clonal Hematopoiesis and IKAROS Loss Cooperate in a B-ALL Subtype after Lenalidomide Therapy for Multiple Myeloma. Blood 2026; blood.2025031047. doi: https://doi.org/10.1182/blood.2025031047 March 13, 2026.
Overview
Lenalidomide is widely used as maintenance therapy after initial myeloma treatment, but it carries a small risk of secondary cancers, including a type of leukemia called B-cell precursor acute lymphoblastic leukemia (B-ALL). This study molecularly characterized 57 patients who developed B-ALL after lenalidomide treatment, identifying three distinct genetic subgroups and proposing a mechanism for one of them.
The three subgroups were defined by their dominant mutations: TP53 mutations in 30% of patients, IDH2 mutations (specifically at position R140Q) in 23%, and a third group including NRAS and KRAS mutations. The IDH2 R140Q mutation was far more common in lenalidomide-associated B-ALL than in B-ALL arising without prior lenalidomide exposure — a statistically significant enrichment that pointed toward a specific drug-related mechanism.
Further investigation of the IDH2-mutated cases found that the mutation was not confined to the leukemia cells. It persisted in patients who had achieved remission with no detectable disease, and it was present in both lymphoid and myeloid cell populations — two different blood cell lineages. That pattern indicates the mutation originated in an early blood stem cell before leukemia developed, a state called clonal hematopoiesis, where a mutated stem cell silently expands without immediately causing disease.
The researchers propose a sequence of events: lenalidomide promotes the expansion of blood stem cells carrying IDH2 mutations, then suppresses a protein called IKAROS that normally drives B-cell maturation. That suppression stalls developing B cells at an immature stage. Additional genetic or epigenetic changes then push those stalled cells toward leukemia — at which point the process becomes independent of continued lenalidomide exposure.
Gene expression and DNA methylation analysis confirmed that IDH2-mutated lenalidomide-associated B-ALL has a molecular profile distinct from other B-ALL subtypes, with features attributable both to the IDH2 mutation and to lenalidomide exposure.
The findings define IDH2-mutated B-ALL as a molecularly distinct subtype of treatment-related leukemia and identify clonal hematopoiesis as a likely prerequisite for its development.
"METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation"
Source
Wang, G., Gao, X., Zhang, H. et al. METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation. Oncogene (2026). https://doi.org/10.1038/s41388-026-03706-y March 13, 2026.
Overview
Proteasome inhibitors are among the most important drugs in myeloma treatment, but resistance to them is common and limits their long-term effectiveness. This study identified a protein called METTL16 as a contributor to that resistance.
METTL16 is known primarily as an RNA-modifying enzyme, but the researchers found that its role in myeloma resistance operates through a different mechanism — one that does not depend on its RNA-modifying activity. Instead, METTL16 alters how the cell controls protein production. Specifically, high METTL16 levels were associated with changes in the interaction between two proteins, PERK and eIF2α, that regulate how much protein the cell makes under stress. In myeloma cells with elevated METTL16, eIF2α was less phosphorylated than normal, which increased translation of specific proteins including PSMB5 — a component of the proteasome itself — and CCND1, which drives cell division. The result was higher proteasome activity and faster cell proliferation.
When the researchers used a drug to inhibit METTL16 in myeloma cells, proteasome inhibitors became more effective. The combination produced greater cell death than either treatment alone.
The findings identify METTL16 as a regulator of proteasome inhibitor sensitivity that acts outside its known enzymatic role, and suggest that blocking it could restore or enhance the effectiveness of proteasome inhibitors in patients whose disease has become resistant. The work was conducted in cell models; clinical testing has not yet been done.
"Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma"
Source
Zeng, F., Taki, A. Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma. Discov Onc (2026). https://doi.org/10.1007/s12672-026-04812-9 March 14, 2026.
Overview
Treatment for multiple myeloma has improved substantially with proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Yet, most patients relapse, and the disease remains incurable for the majority.
A central reason for relapse is drug resistance. Some myeloma cells are resistant before treatment begins; others acquire resistance during it. Both types involve changes in molecular signaling pathways, genetic mutations, and interactions between myeloma cells and the surrounding bone marrow environment that reduce or eliminate a drug's ability to kill them. This review examined the mechanisms behind those resistance patterns.
Understanding which pathways are active in a given patient's disease has practical implications. Genetic profiling of myeloma cells can identify mutations that predict resistance to specific drugs, potentially allowing treatment to be selected or adjusted before resistance becomes clinically apparent. Combining drugs that target different pathways simultaneously may reduce the chance that resistant subpopulations survive and expand.
The review discusses how advances in genomic profiling and functional laboratory assays are being applied to translate molecular findings into treatment decisions — including identifying which drug combinations are most likely to overcome resistance in individual patients.
The field has not yet reached the point where resistance profiling routinely guides treatment selection in standard practice, and prospective data showing that molecularly guided strategies improve survival over standard approaches remain limited.
"Nutritional and immunological scoring systems to predict complications and outcome after anti-B cell maturation antigen chimeric antigen receptor-T therapy in relapsed/refractory multiple myeloma"
Source
Xuezhu Xu, Zujie Lin, Rui Liu, Yun Yang, Wanhong Zhao, Fangxia Wang, Wanggang Zhang, Jie Liu, Bo Lei, Baiyan Wang, Liufang Gu, Aili He, Ju Bai, Nutritional and immunological scoring systems to predict complications and outcome after anti-B cell maturation antigen chimeric antigen receptor-T therapy in relapsed/refractory multiple myeloma, Cytotherapy, 2026, 102781, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2026.102781. March 14, 2026.
Overview
Patients with relapsed or refractory myeloma who receive CAR-T therapy vary considerably in how well they tolerate it. This study examined whether three nutritional and inflammatory scoring tools measured before treatment could identify patients at higher risk of complications or worse outcomes.
The analysis drew on data from 57 patients treated at a single site in the LEGEND-2 phase 1 trial. The three scores assessed were the Controlling Nutritional Status score (CONUT), the Prognostic Nutritional Index (PNI), and the modified Glasgow Prognostic Score (mGPS), each of which uses routine blood markers to estimate nutritional and inflammatory status. All 57 patients had CONUT and PNI scores available; mGPS was calculable in 24.
Nutritional status as measured by these scores declined in the first two weeks after CAR-T infusion before recovering by three weeks — a pattern consistent with the metabolic demands of cytokine release and immune activation during that period.
Each scoring tool predicted a different set of complications. A CONUT score above 4 before treatment was associated with higher rates of severe early neutropenia, disseminated intravascular coagulation, prolonged clotting time, and low fibrinogen — all markers of coagulation dysfunction. A PNI below 36.5 was associated with higher rates of low immunoglobulin levels after treatment. Baseline mGPS correlated with progression-free survival.
The study was small and retrospective, and the mGPS analysis was limited to fewer than half the patients. The findings suggest that routine pre-treatment nutritional scoring could flag patients who need closer monitoring or early supportive care after CAR-T, though prospective validation would be needed before these scores are incorporated into standard pre-treatment assessment.
"Targeted immunoPET imaging of multiple myeloma"
Source
Gary A. Ulaner, Ola Landgren, Targeted immunoPET imaging of multiple myeloma, Seminars in Hematology, 2026, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2026.03.005. March 14, 2026.
Overview
Standard imaging for myeloma has meaningful limitations. FDG-PET/CT, which tracks glucose uptake to identify active disease, misses up to half of myeloma lesions. This review described an emerging alternative called immunoPET, which uses antibodies or antibody fragments labeled with radioactive tracers to locate myeloma cells throughout the body by binding directly to proteins on their surface.
The proteins targeted in myeloma immunoPET agents include CD38, CD46, CD138, BCMA, CS1, VLA-4, and CXCR4 — all expressed at high levels on myeloma cells in most patients. Because the labeled antibody travels through the bloodstream and binds wherever those proteins are present, a single scan can map disease across the entire body without a biopsy.
Clinical applications under investigation go beyond detection. ImmunoPET may help localize disease precisely enough to guide biopsy to the most active lesion, quantify total tumor burden more accurately than current methods, and assess how much disease remains after treatment. One application with particular near-term relevance is predicting response to targeted therapies: CD38-directed immunoPET agents are being tested as a way to measure how much CD38 is present on a patient's myeloma cells before treatment with CD38-targeting drugs, using scan uptake as a predictor of whether those drugs are likely to work.
The same molecular targeting used for imaging can, in principle, be converted into treatment. When the imaging radioisotope is replaced with one that emits high-energy beta or alpha particles — which damage cells rather than just illuminating them — the same antibody construct becomes a radioligand therapy that delivers radiation directly to myeloma cells. Several such agents are in early development.
The field is still investigational. None of the immunoPET agents described in the review have reached routine clinical use in myeloma, and prospective data on whether immunoPET-guided decisions improve patient outcomes are still being collected.
"Blood-based MRD testing in multiple myeloma: Update on mass spectrometry methods for detecting the monoclonal immunoglobulin"
Source
Katie L. Thoren, Blood-based MRD testing in multiple myeloma: Update on mass spectrometry methods for detecting the monoclonal immunoglobulin, Seminars in Hematology, 2026, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2026.03.006. March 14, 2026.
Overview
Myeloma is tracked during and after treatment by measuring a protein produced by the cancer cells, called the M-protein, in the blood. Traditional methods — protein electrophoresis and immunofixation — were adequate when treatments produced modest responses, but they are not sensitive enough to detect the very low disease levels that newer treatments now achieve. Bone marrow biopsy with next-generation sequencing or flow cytometry can detect one malignant cell among a million normal ones, but biopsies are invasive, expensive, and cannot be repeated frequently. They also miss disease that has spread outside the bone marrow.
Mass spectrometry offers a potential alternative: a blood test sensitive enough to detect tiny amounts of M-protein in serum, without a biopsy. Two main technical approaches have been developed. The intact light chain method measures the M-protein directly based on its molecular weight. The clonotypic peptide method breaks the M-protein into fragments and identifies a unique sequence specific to that patient's cancer. Several commercial assays based on these approaches are now available, and some are moving into routine clinical use.
MRD status — whether any detectable disease remains after treatment — is one of the strongest predictors of how long a myeloma patient will stay in remission. Multiple studies have linked MRD negativity to longer progression-free and overall survival, and the FDA's oncology advisory committee endorsed MRD as an endpoint for accelerated drug approvals in myeloma, which will affect how quickly new treatments reach patients.
This review summarized the different mass spectrometry methods for M-protein detection, compared their performance against established bone marrow MRD tests across published studies, and described what further validation would be needed before mass spectrometry can be used as a standalone MRD tool in clinical practice and trials.
"DIS3 mutations enhance AID-driven translocations during B-cell activation, promoting transformation to multiple myeloma"
Source
Kuliński, T.M., Gewartowska, O., Mahé, M. et al. DIS3 mutations enhance AID-driven translocations during B-cell activation, promoting transformation to multiple myeloma. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70386-3 March 14, 2026.
Overview
Multiple myeloma frequently carries mutations in a gene called DIS3, which encodes an enzyme that degrades RNA inside the cell nucleus. These mutations are among the most common genetic alterations in myeloma, but how they contribute to the cancer's development has been unclear. This study used a mouse model and human myeloma samples to trace the mechanism.
DIS3 normally plays a role in a process called class switch recombination, which occurs in B cells when they are activated by infection or vaccination and need to change the type of antibody they produce. This process requires controlled DNA cutting by an enzyme called AID. The researchers found that a specific DIS3 mutation found in myeloma patients — G766R — disrupts the precision of that cutting.
In mice engineered to carry the G766R variant, B cells developed chromosomal translocations — abnormal joins between different chromosomes — that bore the molecular signature of misdirected AID activity. When those mice were exposed to pristane, a chemical that triggers plasma cell tumors, they developed plasmacytomas, an early-stage form of the disease that models the precursor states before myeloma. In human myeloma samples, DIS3 mutations correlated with translocations involving the immunoglobulin heavy chain gene and with AID-associated damage in cancer-driving genes.
The mechanism the researchers identified involves mutated DIS3 protein accumulating on RNA that is bound to chromatin — the packaged form of DNA — at sites where AID should not normally act. This causes AID to create double-strand DNA breaks at those abnormal locations, which are then repaired by a process called microhomology-mediated end joining that produces oncogenic rearrangements. The translocations occurred specifically during class switch recombination, which otherwise proceeded normally.
Critically, the mutation does not disrupt the overall architecture of the genome in activated B cells. Instead, it exploits the normal spatial proximity of chromosomal regions during recombination to permanently fuse enhancers — regulatory elements that amplify gene activity — with proto-oncogenes, converting them into active cancer drivers.
The findings establish that DIS3 mutations drive myeloma development by expanding AID's range of targets during a normal B cell process, producing the chromosomal rearrangements characteristic of the disease without broadly impairing B cell function..
"Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells"
Source
Yusuke Konishi, Tomohiro Omura, Takeshi Ijichi, Hiroki Nishiguchi, Ryunosuke Hayakawa, Yumi Kitahiro, Kotaro Itohara, Kazuhiro Yamamoto, Ikuko Yano, Bortezomib Induces Apoptosis via Upregulation of Abhd4 in Peripheral Nerve Cells, Biological and Pharmaceutical Bulletin, 2026, Volume 49, Issue 3, Pages 496-502, Released on J-STAGE March 14, 2026, Online ISSN 1347-5215, Print ISSN 0918-6158, https://doi.org/10.1248/bpb.b25-00800, https://www.jstage.jst.go.jp/article/bpb/49/3/49_b25-00800/_article/-ch…;
Overview
Multiple myeloma frequently carries mutations in a gene called DIS3, which encodes an enzyme that degrades RNA inside the cell nucleus. These mutations are among the most common genetic alterations in myeloma, but how they contribute to the cancer's development has been unclear. This study used a mouse model and human myeloma samples to trace the mechanism.
DIS3 normally plays a role in a process called class switch recombination, which occurs in B cells when they are activated by infection or vaccination and need to change the type of antibody they produce. This process requires controlled DNA cutting by an enzyme called AID. The researchers found that a specific DIS3 mutation found in myeloma patients — G766R — disrupts the precision of that cutting.
In mice engineered to carry the G766R variant, B cells developed chromosomal translocations — abnormal joins between different chromosomes — that bore the molecular signature of misdirected AID activity. When those mice were exposed to pristane, a chemical that triggers plasma cell tumors, they developed plasmacytomas, an early-stage form of the disease that models the precursor states before myeloma. In human myeloma samples, DIS3 mutations correlated with translocations involving the immunoglobulin heavy chain gene and with AID-associated damage in cancer-driving genes.
The mechanism the researchers identified involves mutated DIS3 protein accumulating on RNA that is bound to chromatin — the packaged form of DNA — at sites where AID should not normally act. This causes AID to create double-strand DNA breaks at those abnormal locations, which are then repaired by a process called microhomology-mediated end joining that produces oncogenic rearrangements. The translocations occurred specifically during class switch recombination, which otherwise proceeded normally.
Critically, the mutation does not disrupt the overall architecture of the genome in activated B cells. Instead, it exploits the normal spatial proximity of chromosomal regions during recombination to permanently fuse enhancers — regulatory elements that amplify gene activity — with proto-oncogenes, converting them into active cancer drivers.
The findings establish that DIS3 mutations drive myeloma development by expanding AID's range of targets during a normal B cell process, producing the chromosomal rearrangements characteristic of the disease without broadly impairing B cell function.
"Role of Radiotherapy in the Era of Novel Immune-Based Treatment Strategies for Multiple Myeloma"
Source
Schlusemann, Tom, Evgenii Shumilov, Gabriele Reinartz, et al. 2026. “Role of Radiotherapy in the Era of Novel Immune-Based Treatment Strategies for Multiple Myeloma,” Hematological Oncology: e70186. https://doi.org/10.1002/hon.70186. March 15, 2026.
Overview
Radiotherapy has long been used in myeloma to relieve pain from bone lesions, prevent fractures, and reduce the risk of neurological complications from tumors pressing on the spinal cord or nerves. Those indications have not disappeared, but the introduction of CAR-T therapy, bispecific antibodies, and monoclonal antibody-based frontline regimens over the past decade has created new situations where radiotherapy is being used in ways that were not previously relevant.
This review summarized the published evidence on combining radiotherapy with each major class of systemic myeloma therapy and examined what is known about safety, feasibility, and efficacy in each setting.
Three newer indications have emerged alongside the older palliative ones. First, radiotherapy is being used as bridging therapy before CAR-T infusion — targeting specific lesions to control disease during the weeks between T cell collection and reinfusion, when patients cannot receive their prior systemic treatment. Second, radiotherapy is being used as salvage treatment after CAR-T failure, particularly for localized disease that has progressed or for extramedullary lesions that were not adequately controlled. Third, in patients on bispecific antibodies who develop progression in only one or a few sites — called oligoprogression — radiotherapy can address those sites without requiring a change in the overall systemic regimen.
The evidence base for these newer combinations is thin. Most data come from small retrospective series, and prospective trials examining the safety and efficacy of combining radiotherapy with bispecific antibodies or CAR-T are limited. Whether radiotherapy enhances or interferes with the immune mechanisms these treatments depend on remains an open question that current data cannot answer.
"IRF2 is an Essential Transcription Factor with Pathogenic and Prognostic Impact in Multiple Myeloma"
Source
Nahia Gómez-Echarte, Arantxa Carrasco-León, Alba Maiqués-Díaz, Naroa Barrena, Estibaliz Miranda, Leire Garate, Ane Amundarain, Patxi San Martín-Uriz, Stella Charalampopoulou, Luis Vitores Valcárcel, Beñat Ariceta, Paula Rodriguez-Marquez, Juan Roberto Rodriguez-Madoz, Kazuya Ishiguro, Francisco J. Planes, Paula Rodriguez-Otero, Constantine S. Mitsiades, José Ignacio Martín-Subero, Edurne San José-Enériz, Felipe Prosper, Xabier Agirre, IRF2 is an Essential Transcription Factor with Pathogenic and Prognostic Impact in Multiple Myeloma, Blood, 2026, ISSN 0006-4971, https://doi.org/10.1182/blood.2025029422. March 16, 2026.
Overview
Transcription factors are proteins that control which genes are switched on or off in a cell. This study used a CRISPR-Cas9 screen — a method that systematically disables individual genes to identify which ones a cancer cell cannot survive without — to find transcription factors essential for myeloma cell survival. The screen identified 22 candidates, including several members of the interferon regulatory factor (IRF) family.
IRF4 is already well established as a myeloma dependency. The study found that a related protein, IRF2, is also essential, a finding that had not previously been recognized. Mapping experiments showed that IRF2 binds extensively across the genome in myeloma cells, both at gene promoters on its own and at intronic regions in cooperation with IRF1 and IRF4. Functionally, IRF2 suppresses a form of cell death called necroptosis and promotes cell migration — two properties that support tumor survival and spread.
The researchers then examined whether IRF2 activity was relevant beyond established myeloma. Gene expression data from patients with MGUS and smoldering myeloma — precursor conditions that precede active disease — showed IRF2-associated transcriptional changes already present at those earlier stages, suggesting it contributes to disease evolution before myeloma is clinically apparent.
In myeloma patients, higher IRF2 expression correlated with shorter progression-free and overall survival. That association held in multivariate analysis after accounting for standard genetic risk factors, indicating IRF2 level carries prognostic information independent of established markers.
Inhibiting IRF2 in myeloma cells disrupted several signaling pathways involved in the disease. No IRF2 inhibitors are currently in clinical use for myeloma; the findings identify it as a candidate target for drug development.
"Descriptive study of current routine clinical practice in the management of patients with multiple myeloma in Spain: CROMMAS study"
Source
Enrique M. Ocio, María-Victoria Mateos, Descriptive study of current routine clinical practice in the management of patients with multiple myeloma in Spain: CROMMAS study, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.004. March 16, 2026.
Overview
Treatment options for myeloma have expanded rapidly, but published guidelines often lag behind clinical practice, and data on what doctors actually prescribe outside of clinical trials are limited. This survey collected treatment pattern data from 23 hematologists working in Spain's public health system, covering both newly diagnosed and relapsed or refractory myeloma.
For patients fit enough for autologous stem cell transplant, the most commonly used induction regimen was daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd), prescribed in 50% of cases, followed by daratumumab, bortezomib, thalidomide, and dexamethasone (23%), and bortezomib, lenalidomide, and dexamethasone (20%). Nearly all transplant-eligible patients — 98% — received maintenance therapy afterward, most commonly lenalidomide alone (77%) or lenalidomide combined with bortezomib (13%).
For patients not eligible for transplant, daratumumab, lenalidomide, and dexamethasone (DRd) was the most frequently prescribed first-line regimen, used in 66% of cases, followed by daratumumab, bortezomib, melphalan, and prednisone (17%).
In patients whose disease had relapsed or become refractory to lenalidomide, the most commonly used second-line regimen was isatuximab, carfilzomib, and dexamethasone (58%), followed by daratumumab, bortezomib, and dexamethasone (14%) and pomalidomide-based combinations (12%).
The survey reflects practice at a single point in time across a small group of specialists and does not capture outcomes. Its value lies in documenting what regimens are being used in routine Spanish clinical practice during a period when treatment options are changing faster than guidelines are being updated.
"Mapping the Landscape of Quality of Life in Smoldering Multiple Myeloma Clinical Trials: A Systematic Review"
Source
Gómez-Almaguer David, Saldaña-Vázquez Roxana, Tarín-Arzaga Luz, Herrera-Rojas Miguel Angel, Vázquez-Mellado de Larracoechea Alberto, Cantú-Rodríguez Olga Graciela, Gutiérrez-Aguirre Cesar Homero, Jaime-Pérez José Carlos, "Mapping the Landscape of Quality of Life in Smoldering Multiple Myeloma Clinical Trials: A Systematic Review", Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.006. March 16, 2026.
Overview
Smoldering myeloma is a precursor condition that sits between the benign protein abnormality called MGUS and active myeloma requiring treatment. As trials have shown that early treatment can delay progression and, in some cases, improve survival in high-risk patients, the question of whether treatment also affects how patients feel and function has become more pressing. Treatment can cause side effects; watchful waiting carries its own anxieties. Both can affect quality of life, and neither is well captured by survival data alone.
This systematic review searched six databases for clinical trials testing drug treatments in smoldering myeloma, with the aim of identifying how often and how well those trials measured health-related quality of life.
The central finding was that most trials did not measure quality of life at all. Only four randomized trials included quality of life as an outcome, and only two reported enough detail to be interpretable. Both — the AQUILA and ECOG-ACRIN trials — reported improvements in quality of life, but those improvements appeared specific to the treatments studied rather than reflecting a generalizable pattern across interventions.
The authors frame this not only as a methodological gap but as an ethical one. When doctors and patients weigh whether to treat a condition that may never progress to active disease, or may not do so for many years, information about how treatment affects daily life is directly relevant to that decision. Trials that measure only disease progression or survival provide an incomplete basis for those conversations.
As more treatments enter trials for smoldering myeloma, systematic inclusion of validated quality of life measures from the outset would allow treatment comparisons that reflect patient experience alongside biological outcomes.
"Obesity Accelerates Multiple Myeloma Progression in Certain Mouse Models and in Humans"
Source
Heather Fairfield, Catherine R. Marinac, Habib Hamidi, Katherine Knox, Brian Nestor, Constance Marques-Mourlet, Giovanni Diaz, Cheryl V. Wong, Ameet K. Mishra, Allyson Schimelman, Ya-Wei Qiang, Michelle Karam, Mariah Farrell, Edward Jachimowicz, J Patrizia. Stohn, Brenda M. Birmann, Peter Cornelius, Michaela R. Reagan; Obesity Accelerates Multiple Myeloma Progression in Certain Mouse Models and in Humans. Cancer Prev Res (Phila) 2026; https://doi.org/10.1158/1940-6207.CAPR-25-0213 March 16, 2026.
Overview
Obesity is associated with higher myeloma risk and worse survival, making it a potential target for prevention. Studying that relationship in the laboratory requires animal models that accurately reproduce the effect — but not all myeloma mouse models respond to obesity the same way. This study tested three established mouse models under high-fat diet conditions to identify which one captures obesity-driven myeloma acceleration.
The three models tested were a SCID-beige xenograft using human myeloma cells, a syngeneic model using Vk*MYC myeloma cells in C57BL/6J mice, and a semi-syngeneic model using 5TGM1 myeloma cells in C57BL/6J mice. Only the third — the 5TGM1 semi-syngeneic model — showed obesity-accelerated disease. Obese mice in that model had higher myeloma incidence, higher serum IgG levels, and stronger tumor bioluminescent signal than lean controls. The other two models did not reproduce the effect.
The 5TGM1 model used here is the first to track myeloma engraftment in obese mice using bioluminescent imaging, which allows tumor growth and clearance to be monitored non-invasively over time in the same animal. That capability makes it suitable for testing how obesity-related factors — including immune dysfunction — contribute to myeloma progression, and for evaluating interventions aimed at disrupting that relationship.
The researchers also analyzed clinical data from the MMRF CoMMpass study, a large longitudinal dataset of myeloma patients. Moderate and severe obesity at diagnosis were associated with higher mortality. Gene expression analysis identified differences in the molecular profiles of myeloma cells from obese versus normal-weight patients, pointing toward specific pathways that may mediate the obesity-cancer relationship.
The mouse model and the clinical associations together support obesity as a biologically active contributor to myeloma progression rather than a passive risk marker.
"VS-4718 enhances apoptosis induced by low-dose carfilzomib and overcomes carfilzomib resistance in PSMB5-mutated proteasome inhibitor resistant multiple myeloma"
Source
Leich-Zbat, E., Heredia-Guerrero, S.C., Evers, M. et al. VS-4718 enhances apoptosis induced by low-dose carfilzomib and overcomes carfilzomib resistance in PSMB5-mutated proteasome inhibitor resistant multiple myeloma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43205-4 March 16, 2026.
Overview
Proteasome inhibitors are central to myeloma treatment, but resistance develops in many patients and the drugs carry significant side effects at full doses. This study tested whether combining a drug called VS-4718 — which blocks two signaling enzymes, PYK2 and FAK — with the proteasome inhibitor carfilzomib could produce effective anti-myeloma activity at lower carfilzomib doses, and whether it could restore sensitivity in cells already resistant to proteasome inhibitors.
The experiments were conducted in seven standard human myeloma cell lines and in cell lines engineered to be resistant to three proteasome inhibitors simultaneously.
In the standard cell lines, VS-4718 reduced cell viability in a dose-dependent manner across all seven lines. The effect did not depend on whether the cells expressed high or active levels of PYK2, suggesting VS-4718 acts through a mechanism beyond direct PYK2 inhibition. When combined with carfilzomib, the two drugs produced more than additive cell death in five of the seven lines. Titration experiments using low and sublethal carfilzomib doses showed that the combination retained specific anti-tumor activity while having little effect on normal immune cells from peripheral blood — a finding relevant to tolerability.
In the triple-resistant cell lines, adding VS-4718 to carfilzomib restored sensitivity to the proteasome inhibitor and again produced more than additive reduction in cell survival.
The results suggest this combination warrants further investigation as a lower-toxicity approach for relapsed or refractory myeloma, including in patients whose disease has become resistant to proteasome inhibitors. The work was conducted in cell models; animal and clinical studies would be needed to evaluate the combination's behavior in vivo.
"CD38-Targeted Small-Molecule PET Radiotracer for Noninvasive Tumor Evaluation and Preliminary Therapy Monitoring in Multiple Myeloma"
Source
Duan C, Guo S, Xu P, Han W, Lu Y, Guo Z, Fu P, Liu G, Zhao C. CD38-Targeted Small-Molecule PET Radiotracer for Noninvasive Tumor Evaluation and Preliminary Therapy Monitoring in Multiple Myeloma. J Med Chem. 2026 Mar 16. doi: 10.1021/acs.jmedchem.5c03340. Epub ahead of print.
Overview
CD38 is a protein expressed on myeloma cells and is the target of several approved antibody drugs, including daratumumab. How much CD38 a patient's myeloma expresses may influence how well those drugs work, but current methods for measuring CD38 require a bone marrow biopsy and capture only a single location. This study developed and tested small-molecule PET tracers designed to measure CD38 expression non-invasively across the whole body.
The researchers synthesized a series of gallium-68-labeled compounds and evaluated their stability and imaging properties. One compound, 68Ga-NOTA-MK0159, performed best. In myeloma animal models, PET/CT signal from the tracer correlated with CD38 expression levels — higher signal in tumors with more CD38, lower signal in tumors with less. Administering excess unlabeled MK-0159 blocked tracer uptake, confirming the signal was specific to CD38 binding rather than nonspecific accumulation.
The most clinically relevant finding was that daratumumab did not block tracer uptake under the experimental conditions tested. Daratumumab binds to CD38 and could in principle occupy the binding site and prevent the tracer from attaching, which would make imaging during treatment uninformative. The fact that the tracer and daratumumab appear to bind at different sites on CD38 suggests the tracer could be used to monitor CD38 expression in patients who are already receiving daratumumab — potentially identifying whether CD38 levels are changing during treatment in ways that might predict response or resistance.
The findings are preclinical. Whether 68Ga-NOTA-MK0159 performs similarly in patients, and whether CD38 PET imaging improves treatment decisions in practice, would require clinical studies.
"Geriatric nutritional risk index predicts 10-year survival in patients with multiple myeloma"
Source
Kazuhito Suzuki, Tadahiro Gunji, Riku Nagao, Hideki Uryu, Hiroki Yokoyama, Atsushi Katsube, Hiroto Ishii, Daiki Hattori, Yasutaka Mochizuki, Mitsuji Katori, Kei Hirano, Takashi Nakamura, Keita Ishii, Kaichi Nishiwaki, Shingo Yano, Geriatric nutritional risk index predicts 10-year survival in patients with multiple myeloma, Japanese Journal of Clinical Oncology, 2026;, hyag040, https://doi.org/10.1093/jjco/hyag040 March 16, 2026.
Overview
Most myeloma patients do not survive ten years from diagnosis, but roughly one in five does. Identifying what distinguishes long-term survivors from others could help clinicians target supportive interventions and set more individualized expectations. This retrospective study examined whether nutritional status at diagnosis — alongside disease characteristics — predicted long-term survival in 163 newly diagnosed myeloma patients treated between 2009 and 2014.
Nutritional status was measured using the Geriatric Nutritional Risk Index (GNRI), a score calculated from height, weight, and serum albumin. A GNRI above 91.7 was identified as the threshold separating higher and lower nutritional status groups.
21% of patients survived ten or more years. Patients with higher GNRI scores at diagnosis had lower rates of CRAB symptoms — the organ damage criteria used to define active myeloma — and were less likely to have advanced-stage disease by ISS classification.
Ten-year overall survival was 39.6% in the high GNRI group versus 27.9% in the low GNRI group. In multivariate analysis, high GNRI and the absence of early disease progression were both independently associated with longer survival. Among patients with high GNRI who did not experience early progression, ten-year survival reached 49.2%.
The study was retrospective and drew from a single center over a period when treatment options were less advanced than they are now, which limits how directly the findings apply to patients treated with current regimens. The results suggest nutritional status at diagnosis carries prognostic information beyond standard staging, though whether nutritional interventions before or during treatment improve long-term outcomes would require prospective study.
"CD8+CD38+ T cells Identify Functional High-Risk Multiple Myeloma After Autologous Transplant"
Source
Nezar Mehanna, Andriy Derkach, Billel Gasmi, Theodora Anagnostou, Heather J. Landau, Oscar B. Lahoud, Michael Scordo, Gunjan L. Shah, Hani Hassoun, Kylee Maclachlan, Malin Hultcrantz, Neha Korde, Sham Mailankody, Urvi A. Shah, Carlyn R. Tan, Saad Z. Usmani, Sergio A. Giralt, Alexander M. Lesokhin, David J. Chung, CD8+CD38+ T cells Identify Functional High-Risk Multiple Myeloma After Autologous Transplant: BTM CTN 0702 Correlates, Blood Neoplasia, 2026, 100221, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2026.100221. March 17, 2026.
Overview
Patients whose myeloma returns within 24 months of autologous stem cell transplant have shorter overall survival than those who maintain longer remissions. Identifying those patients early — before relapse occurs — would allow closer monitoring and potentially earlier intervention. This study examined whether immune cell profiles in the blood and bone marrow at day 100 after transplant could distinguish patients likely to relapse early from those likely to stay in remission.
The researchers first analyzed bone marrow samples from 110 myeloma patients with long-term follow-up using immunohistochemistry. CD3+PD-1+ T cells — a marker of activated T cells — were associated with early relapse independently of maintenance therapy and genetic risk factors, suggesting the immune environment after transplant carries prognostic information beyond standard risk markers.
To refine that finding, the researchers analyzed peripheral blood samples from 96 participants in the BMT CTN 0702 clinical trial: 45 who relapsed within 24 months and 51 who remained in remission beyond four years. Using high-dimensional flow cytometry and unsupervised clustering, they identified differences in several T cell markers between the two groups, including HLA-DR, granzyme B, CTLA4, CD27, TIGIT, and CD38. After statistical variable reduction, CD38 expression on a specific CD8+ T cell subset — defined by co-expression of the transcription factor Eomes and associated with effector memory function — was the single most predictive feature, with an area under the curve of 86% for distinguishing early relapse from long-term remission. The finding was confirmed in an independent cohort of 18 patients.
A blood draw at day 100 post-transplant is already standard practice for monitoring recovery. Whether measuring this T cell signature at that time point could guide treatment decisions — such as maintenance therapy intensification — would require prospective validation.
"Choosing Wisely in First Relapse of Multiple Myeloma: Expert Insights on Treatment Selection"
Source
Samer Al Hadidi, Caitlin Costello, Luciano J. Costa, Binod Dhakal, Peter Georges, Ajeet Gajra, Yi Lin, Ranjana S Bhargava, Agne Paner-Straseviciute, Ravi Vij, Choosing Wisely in First Relapse of Multiple Myeloma: Expert Insights on Treatment Selection, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.009. March 17, 2026. .
Overview
Most myeloma patients relapse after initial treatment, and selecting what to use next is increasingly complex. The number of available drug combinations has grown, each with different mechanisms, toxicity profiles, and implications for what can be used afterward. This review summarized practical guidance from experienced clinicians on how to approach treatment selection at first relapse.
Several patient and disease factors shape that decision: age, functional status, other health conditions, chromosomal risk features, which drugs were used in initial treatment, and how long the first remission lasted. The choice at second line also affects third line and beyond — drugs that exhaust certain targets or damage T cell function may limit options later, including eligibility for CAR-T therapy and bispecific antibodies.
CAR-T therapy and bispecific antibodies targeting BCMA and other myeloma antigens have become important options in later lines of treatment, and their availability has changed how earlier treatment decisions should be framed. Preserving T cell fitness and avoiding agents that compromise it is relevant for patients who may be candidates for these therapies in the future.
CAR-T logistics introduce an additional planning consideration. Manufacturing takes three to four weeks or longer depending on the product, and patients need effective disease control during that window. Without adequate bridging therapy between the collection of T cells (apheresis) and infusion, disease can progress substantially before treatment is delivered. Early referral to a CAR-T center — before the patient has exhausted other options and while they are still in adequate condition — allows time for manufacturing and for selecting appropriate bridging treatment. The review recommends referral well before CAR-T is immediately needed rather than waiting until it becomes the only remaining option.
"Surface-enhanced Raman spectroscopy for the characterization of filtrate portions of blood serum samples of Multiple Myeloma patients using 50kDa filtration devices and Ag-NPs as SERS substrat"
Source
Adeela Ismail, Samra Ashfaq, Muhammad Irfan Majeed, Haq Nawaz, Nosheen Rashid, Najah Alwadie, Laraib Kiran, Allah Ditta, Rifsha Rabbani, Fozia Sarfraz, Areej, Saira Ramzan, Farzana Shamim, Muhammad Arslan, Muhammad Imran, Surface-enhanced Raman spectroscopy for the characterization of filtrate portions of blood serum samples of Multiple Myeloma patients using 50kDa filtration devices and Ag-NPs as SERS substrate, Vibrational Spectroscopy, 2026, 103911, ISSN 0924-2031, https://doi.org/10.1016/j.vibspec.2026.103911. March 17, 2026.
Overview
Diagnosing and monitoring myeloma currently relies on blood tests, bone marrow biopsies, and imaging. This study explored whether a technique called surface-enhanced Raman spectroscopy (SERS) could detect myeloma-associated changes in blood serum without a biopsy, by analyzing the molecular fingerprint of small molecules in the blood.
SERS works by shining a laser on a sample placed on a surface coated with silver nanoparticles. The nanoparticles amplify the light signals scattered by molecules in the sample, producing a spectrum of peaks that reflect the molecular composition. Different diseases alter the balance of molecules in the blood, potentially producing distinct spectral patterns.
One technical challenge is that blood serum contains both large and small molecules, and the large ones tend to dominate the signal, masking smaller molecules that may be more informative for early disease detection. The researchers addressed this by filtering serum samples through a membrane that retains molecules above 50 kilodaltons, then analyzing only the smaller molecules that passed through.
Comparing filtered serum from myeloma patients and healthy controls, the researchers identified five spectral peaks — at 561, 797, 988, 1167, and 1538 cm⁻¹ — that differed between the two groups. They then applied statistical classification methods to determine whether those spectral differences could reliably distinguish myeloma from healthy samples. A model using partial least squares discriminant analysis achieved an area under the ROC curve of 0.92, indicating strong discriminatory performance in this dataset.
The study was conducted on a limited number of samples in controlled laboratory conditions. Validation in larger, more diverse patient cohorts — including patients at different disease stages and with other plasma cell disorders — would be needed before this approach could be considered for clinical use.
"Covalent JAK3 inhibitors based on 2-arylamino and 7H-pyrrolo[2,3-d]pyrimidine scaffold: design, synthesis, and biological evaluation for the potential treatment of Bortezomib-resistant multiple myeloma"
Source
Liangliang Tian, Jiaxun Li, Jiawen Yu, Qingxuan Han, Nafiseh Bolghanabadi, Ke Wang, Zhiping Chen, Xu Zheng, Peng Chu, Lixue Chen, Covalent JAK3 inhibitors based on 2-arylamino and 7H-pyrrolo[2,3-d]pyrimidine scaffold: design, synthesis, and biological evaluation for the potential treatment of Bortezomib-resistant multiple myeloma, European Journal of Medicinal Chemistry, 2026, 118764, ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2026.118764. March 17, 2026.
Overview
Bortezomib is a proteasome inhibitor used in most myeloma treatment regimens, but resistance — both present at the start of treatment and acquired during it — limits its long-term effectiveness. One mechanism that has been linked to resistance is persistent activation of the JAK/STAT signaling pathway, which promotes cell survival. This study designed and tested a series of compounds aimed at blocking JAK3, a key enzyme in that pathway, with the goal of overcoming bortezomib resistance.
The researchers synthesized a series of small molecules and screened them for JAK3 inhibitory activity. The most promising compound, designated 7n, bound JAK3 with an IC50 of 0.75 nM — a measure of potency indicating that very low concentrations were sufficient to inhibit half the enzyme activity. Against bortezomib-resistant myeloma cells in culture, 7n inhibited cell growth with an IC50 of 0.25 µM. When tested against a panel of 76 kinases, 7n showed 97% inhibition of JAK3 at 5 nM, with the strongest selectivity for JAK3 in the panel.
In bortezomib-resistant myeloma cells, 7n reduced cell migration, increased apoptosis, and suppressed JAK-STAT pathway activity. In mice carrying bortezomib-resistant myeloma tumors, 7n reduced tumor growth. Pharmacokinetic testing showed the compound achieved 39% oral bioavailability, meaning it can be absorbed when taken by mouth — a practical consideration for drug development.
The findings support JAK3 as a relevant target in bortezomib-resistant myeloma and identify 7n as a candidate for further preclinical development. No human studies have been conducted.
"A review of the clinical efficacy of monoclonal antibody (mAb)-based therapies for relapsed/refractory multiple myeloma (RRMM)"
Source
Liu, Y., Lee, J. H., Mo, C. C., Salman, T. J., Hossain, S., Midha, S., … Richardson, P. G. (2015). A review of the clinical efficacy of monoclonal antibody (mAb)-based therapies for relapsed/refractory multiple myeloma (RRMM). Expert Opinion on Biological Therapy. https://doi.org/10.1080/14712598.2026.2646947 March 17, 2026.
Overview
Four antibody-based drugs have established roles in relapsed or refractory myeloma: daratumumab and isatuximab, which target CD38; elotuzumab, which targets SLAMF7; and belantamab mafodotin, an antibody-drug conjugate that delivers a cytotoxic payload to cells expressing BCMA. This review examined the mechanisms, efficacy data, real-world effectiveness, and key safety considerations for each, along with how their roles are shifting as the treatment landscape changes.
Daratumumab and isatuximab have moved well beyond relapsed disease — both are now part of standard frontline regimens. That shift has a direct consequence for later lines: patients who relapse after daratumumab-containing induction are anti-CD38 exposed, and often refractory, by the time they need second or third-line treatment. What these drugs can contribute in that more heavily pretreated population, and how to sequence them relative to CAR-T and bispecific antibodies, is an active clinical question.
Belantamab mafodotin targets BCMA, the same antigen as most approved CAR-T products and several bispecific antibodies. How to sequence BCMA-directed therapies — whether prior ADC exposure affects response to subsequent CAR-T or bispecific therapy, and vice versa — is not yet resolved by available data.
The review also covers antibody and ADC combinations under investigation beyond the four approved agents, including those targeting newer antigens.
The authors identify two priorities for the field: developing immune biomarkers that predict which patients will respond to specific antibody-based regimens, and generating prospective sequencing data to inform rational treatment ordering across the growing number of available options.
"IRX4204 sensitizes multiple myeloma to ferroptosis and improves lenalidomide efficacy through the HMOX1-GPX4 axis"
Source
Wu, J., Yan, Z., Burcher, K. et al. IRX4204 sensitizes multiple myeloma to ferroptosis and improves lenalidomide efficacy through the HMOX1-GPX4 axis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42123-9 March 17, 2026.
Overview
Ferroptosis is a form of cell death driven by iron accumulation and lipid oxidation damage, distinct from the apoptosis pathways that most current myeloma drugs target. Whether myeloma cells can be pushed toward ferroptosis, and how to achieve that, has not been well characterized. This study identified a drug that sensitizes myeloma cells to ferroptotic death by activating a transcription factor called RXR.
The compound tested was IRX4204, a third-generation RXR agonist. In myeloma cell lines, IRX4204 increased susceptibility to ferroptotic stress and produced synergistic cell death when combined with drugs that directly induce ferroptosis. The researchers then traced the mechanism.
IRX4204 activates transcription of a gene called HMOX1 through a complex involving PPARα and RXRα. At the same time, it reduces levels of GPX4, an enzyme that normally protects cells from lipid peroxidation damage. The combined effect — more HMOX1 activity and less GPX4 protection — leads to iron accumulation and oxidative lipid damage, triggering ferroptosis. When HMOX1 was deleted using CRISPR, the ferroptosis-sensitizing effects of IRX4204 were abolished, confirming HMOX1 as the essential intermediary.
In animal models, IRX4204 combined with lenalidomide reduced tumor burden, extended survival, and increased ferroptosis markers compared to either drug alone, without added toxicity. In clinical myeloma datasets, higher HMOX1 expression correlated with longer overall survival.
The findings describe an RXR–HMOX1–GPX4 regulatory axis that controls ferroptosis sensitivity in myeloma and identify RXR activation as a strategy for enhancing it. The work was conducted in cell and animal models; clinical testing has not yet been done.
"Elranatamab Versus Teclistamab in Relapsed and Refractory Multiple Myeloma: A Real-World Propensity Score-Matched Study"
Source
Wang, YC., Li, PH., Lin, CH. et al. Elranatamab Versus Teclistamab in Relapsed and Refractory Multiple Myeloma: A Real-World Propensity Score-Matched Study. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01209-0 March 17, 2026.
Overview
Elranatamab and teclistamab are both bispecific antibodies that redirect T cells to kill myeloma cells by targeting BCMA. Both are approved for relapsed or refractory myeloma, but they have not been compared directly in a randomized trial. This retrospective study used electronic health record data from a multinational research network to compare outcomes and side effects between the two drugs in routine clinical practice.
After propensity score matching to balance patient characteristics between groups, 188 patients receiving elranatamab and 188 receiving teclistamab were included. Median time to the next treatment — a proxy for how long the current treatment remained effective — was 11.0 months with elranatamab and 12.3 months with teclistamab, a difference that did not reach statistical significance. Three-year overall survival rates were 58.8% and 59.7% respectively, also not significantly different.
Two subgroups showed a longer time to next treatment with teclistamab: patients with low platelet counts at baseline, and those who had received more than five prior lines of treatment.
The two drugs differed in their side effect profiles. Grade 3 or higher neutropenia was more common with teclistamab (85% versus 75%). Cytokine release syndrome — an immune reaction that occurs when T cells are activated — occurred more often with elranatamab (45% versus 27%). Rates of neurological toxicity and infections were similar between the two groups.
The study's retrospective design and reliance on matched observational data limit causal conclusions. The findings suggest that the two drugs produce comparable effectiveness in routine practice but differ in toxicity in ways that may influence choice for individual patients — particularly those with low platelets or prior neutropenia, where the higher neutropenia rate with teclistamab is relevant, and those at higher infection risk, where the more frequent cytokine release syndrome with elranatamab warrants consideration..
"Daratumumab, bortezomib and dexamethasone for previously treated myeloma—Real-world outcomes for 2545 patients treated in England"
Source
Lawton, S.L., Bishton, M., Thackray, K.E., Kipps, E. and Smith, D. (2026), Daratumumab, bortezomib and dexamethasone for previously treated myeloma—Real-world outcomes for 2545 patients treated in England. Br J Haematol. https://doi.org/10.1111/bjh.70425 March 17, 2026.
Overview
This analysis presents outcomes from 2,545 patients treated with daratumumab, bortezomib, and dexamethasone (D-Vd) at first relapse through the NHS England Cancer Drugs Fund between March 2019 and June 2021 — the largest population-based dataset for this regimen in second-line myeloma to date.
Median age was 70 years. 70% had prior bortezomib exposure and 42% had received a prior stem cell transplant. Median time to next treatment was 16.9 months and median overall survival was 51.8 months across the full cohort.
Prior bortezomib exposure was the strongest predictor of shorter outcomes. Patients who had not previously received bortezomib had a median time to next treatment of 22.7 months versus 15.6 months in those who had, and overall survival was not reached versus 49.8 months. Prior lenalidomide exposure did not significantly affect time to next treatment, though it was associated with shorter overall survival (43.4 versus 53.6 months). This is the largest dataset for D-Vd second-line treatment in patients with prior lenalidomide exposure, with 275 such patients compared to 15 in the CASTOR trial.
Prior transplant did not affect time to next treatment, suggesting D-Vd produces similar disease control in transplant-ineligible patients. Overall survival was longer in patients who had received a prior transplant, though that group was substantially younger — median age 65 versus 74 years — making the survival difference likely attributable to age and fitness rather than transplant history.
Better functional status at baseline (ECOG 0 versus 1 or above) was associated with longer time to next treatment and longer overall survival. Older patients had shorter overall survival but, counterintuitively, longer time to next treatment than younger patients — a pattern the authors attribute partly to older patients being observed for longer before starting the next treatment, and partly to higher rates of prior bortezomib exposure in younger patients.
Compared to the CASTOR trial's one-prior-line cohort, real-world outcomes were shorter: overall survival 51.8 months versus not reached, and time to next treatment 16.9 versus 27 months. The real-world cohort was older (median 70 versus 63 years) and had more prior bortezomib exposure (70% versus 51%), which likely accounts for most of that difference.
"Next Generation Flow and Next Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma Patients: A Real-Life Italian Multicenter Harmonization Experience"
Source
S.Oliva, M.Martello, E.Saraci, et al., “Next Generation Flow and Next Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma Patients: A Real-Life Italian Multicenter Harmonization Experience,” Cancer Medicine15, no. 3 (2026): e71678, https://doi.org/10.1002/cam4.71678. March 17, 2026
Overview
Measuring minimal residual disease (MRD) — detecting tiny numbers of remaining myeloma cells after treatment — has become one of the most important tools for assessing how well treatment is working. Patients who achieve MRD negativity, meaning no detectable disease by sensitive testing, have longer remissions and better survival than those who do not. Two methods are used: next-generation flow cytometry (NGF), which identifies myeloma cells by their surface protein patterns, and next-generation sequencing (NGS), which tracks unique genetic sequences from a patient's myeloma cells.
A practical problem is that results from different laboratories are not always comparable, which limits the ability to combine data across centers or use results interchangeably in clinical trials. The Italian MM-MRD network project tested how consistently these methods perform across multiple laboratories.
Seven laboratories participated in the flow cytometry workgroup, all using the same standardized protocol. When operators at different centers analyzed the same pre-prepared samples (Stage 1), agreement was high (intraclass correlation coefficient 0.90). When the same laboratories analyzed bone marrow samples from actual patients processed independently at each site (Stage 2), agreement was moderate (ICC 0.63). Detection sensitivity reached the target level of one myeloma cell in 100,000, with a median limit of detection of 8 in a million.
Four laboratories participated in the sequencing workgroup. The first quality control round, focused on identifying the unique genetic marker from each patient's myeloma, achieved 100% agreement. Subsequent rounds measuring MRD in standardized test samples achieved 81% and then 91% concordance, with 95% and 83% of samples reaching the target sensitivity level respectively.
The results show that both methods can achieve the required sensitivity across multiple sites, but that real-world sample variability introduces more discordance than controlled conditions suggest. The network is expanding with the aim of reducing that variability through further protocol standardization.
"Early intervention for high-risk smoldering multiple myeloma (SMM)"
Source
Chen PH, Jhou HJ, Ho CL, Huang HL, Lee CH. Early intervention for high-risk smoldering multiple myeloma (SMM). Cochrane Database Syst Rev. 2026 Mar 18;3:CD015494. doi: 10.1002/14651858.CD015494.pub2. March 18, 2026.
Overview
Smoldering myeloma sits between a benign protein abnormality called MGUS and active myeloma requiring treatment. People with high-risk smoldering myeloma have a substantially higher chance of progressing to active disease within a few years.
Whether treating before symptoms appear improves outcomes — and which drugs are worth using — has been an active area of debate. This Cochrane systematic review pooled data from seven randomized controlled trials (1,096 participants) comparing early intervention against observation or placebo in high-risk smoldering myeloma.
The trials tested four drug classes: one monoclonal antibody (daratumumab, one trial, 390 participants), immunomodulatory agents including lenalidomide and thalidomide (three trials, 427 participants), alkylating agents (two trials, 195 participants), and a cytokine inhibitor, siltuximab (one trial, 85 participants). Follow-up ranged from 29 months to 150 months across studies.
Daratumumab produced the clearest signal. Compared to active monitoring, it reduced the risk of progression or death by roughly half (HR 0.49) and reduced the risk of death (HR 0.52). Both findings were rated low-certainty, meaning the true effect may differ from the estimate, primarily because the evidence comes from a single trial. Adverse event data were rated very uncertain. Quality of life showed little difference between groups, also with very uncertain evidence.
For immunomodulatory agents, pooled analyses showed little to no difference from observation for progression-free survival, overall survival, or quality of life. Results conflicted between lenalidomide and thalidomide, and heterogeneity between trials was substantial, leaving the evidence at very low certainty.
Evidence for siltuximab and for melphalan-prednisone was insufficient to draw conclusions about either efficacy or harm.
The review concludes that daratumumab may reduce progression and death in high-risk smoldering myeloma, but that the evidence base remains limited and the safety picture uncertain. The authors recommend individualized risk-benefit discussion rather than a uniform treatment policy.
"Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings"
Source
Janakiram, M., Fan, L., Ghosh, S., Alegria, V., Perciavalle, M., Emond, B., … Dima, D. (2026). Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings. Journal of Medical Economics, 29(1), 871–884. https://doi.org/10.1080/13696998.2026.2640811 March 18, 2026.
Overview
Ciltacabtagene autoleucel (cilta-cel) is a CAR-T therapy approved for relapsed or refractory myeloma after four or more prior lines of treatment. It has traditionally been given in an inpatient setting to allow monitoring for cytokine release syndrome and other early complications, but outpatient administration is increasingly used at centers with appropriate monitoring infrastructure. This study compared hospital resource use and clinical outcomes between the two approaches using insurance claims data from 242 patients treated between February 2022 and June 2024.
148 patients (61%) received cilta-cel as inpatients and 94 (39%) as outpatients. Baseline characteristics were comparable between groups.
In the three months after infusion, the outpatient group used substantially fewer inpatient days — 2.4 per patient per month versus 6.6 in the inpatient group. Nearly a third of outpatient recipients (32%) required no inpatient admission at all during that period. Outpatient visits were more frequent in the outpatient group, as expected. From month four onward, hospital resource use was similar between the two groups.
Rates of cytokine release syndrome and neurological toxicity were comparable. Six-month and twelve-month treatment-free interval and overall survival did not differ significantly between groups.
The findings suggest that outpatient cilta-cel administration produces similar safety and effectiveness outcomes as inpatient administration while reducing inpatient bed use in the months immediately following infusion. The study was observational and based on claims data, which captures resource use but not all clinical detail. Patient selection for outpatient administration — centers likely chose lower-risk patients or those with stronger support systems — may have contributed to the comparable outcomes observed
"Effective resolution of daratumumab-induced false-positive antibody screening with commercial reagents"
Source
Kim HJ, Seo SW, Chung Y, Kim H, Hwang S-H, Oh H-B, et al. Effective resolution of daratumumab-induced false-positive antibody screening with commercial reagents. Vox Sang. 2026. March 18, 2026.
Overview
Daratumumab is an antibody drug used in myeloma treatment that targets a protein called CD38. CD38 is also present on the surface of donor red blood cells used in laboratory testing, which means daratumumab remaining in a patient's blood can falsely react with all donor cells tested — making it appear as though the patient has antibodies against multiple blood types when they do not. This interferes with pre-transfusion compatibility testing and can delay safe blood transfusions.
The standard method for removing this interference involves treating the test red blood cells with a chemical called dithiothreitol (DTT), which strips CD38 from the cell surface. DTT works, but it also removes other blood group antigens, meaning some clinically significant antibodies — particularly those in the Kell blood group system — cannot be detected after treatment. The process is also labor-intensive and produces inconsistent results in some cases.
This study tested a commercial reagent called DaraEx, which contains anti-CD38 antibody fragments that block daratumumab from binding to test cells without removing other surface antigens. Twenty-two blood samples from 17 patients on daratumumab were tested using both methods.
All samples showed false-positive panreactivity before treatment. After treatment, 19 samples were negative with both DTT and DaraEx. Three samples remained reactive after DTT treatment but became negative with DaraEx. Those three cases had lower albumin levels, reduced kidney function, and higher monoclonal protein levels — factors that may affect how daratumumab behaves in the blood. DaraEx-treated cells retained reactivity with anti-E and anti-D antibodies, confirming that clinically important antibodies remain detectable.
DaraEx removed daratumumab interference completely in all samples, including the three where DTT failed, and preserved detection of other clinically relevant antibodies.
"Elranatamab in Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Emerging Perspectives"
Source
M. E.Alvaro, E. A.Martino, S.Caserta, et al., “Elranatamab in Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Emerging Perspectives,” European Journal of Haematology (2026): 1–13, https://doi.org/10.1111/ejh.70167. March 18, 2026.
Overview
Elranatamab is a bispecific antibody that simultaneously binds BCMA on myeloma cells and CD3 on T cells, physically linking the two and triggering T cell-mediated killing of the myeloma cell. Unlike standard monoclonal antibodies, it does not depend on the immune system having previously recognized the tumor — it activates T cells directly at the tumor surface regardless of prior exposure. It is given by subcutaneous injection, which supports outpatient administration in appropriate patients.
A step-up dosing schedule is used at initiation: two lower priming doses (12 mg then 32 mg) are given before the first full 76 mg dose, with weekly dosing continuing through the initial treatment phase. Patients who achieve a sustained response after six cycles can transition to every-two-week dosing. This de-intensification is built into the treatment design rather than being optional — it reduces cumulative immune activation and the infection risk that comes with it.
The main efficacy data come from MagnetisMM-3, a phase 2 single-arm trial in 123 patients with BCMA-naïve relapsed or refractory myeloma who had received a median of four or more prior lines of treatment. The overall response rate was 61%, and 35% achieved a complete response or better. Responses occurred quickly — median time to first response was 1.2 months — and frequently deepened over time. At 15 months of follow-up, median duration of response, progression-free survival, and overall survival had not been reached. Among the 50 evaluable responders who had switched to every-two-week dosing at least six months before data cutoff, 80% maintained or improved their response and 40% deepened further.
The safety profile follows a predictable two-phase pattern. In the first weeks of treatment, cytokine release syndrome (CRS) is the dominant concern, occurring in 58% of patients in MagnetisMM-3, almost always during the first three doses and almost always low grade. Median onset was two days and median duration was two days. Neurological toxicity occurred at low rates and was not a major dose-limiting issue. As treatment continues, the dominant risks shift: infections occurred in 70% of patients and grade 3 or 4 infections in 40%; anemia and neutropenia each occurred in 49%, with high-grade events in 37% and 49% respectively.
After switching to every-two-week dosing, the rate of grade 3 or 4 adverse events fell from 59% to 47% in responders. Successful long-term use requires proactive infection prophylaxis, immunoglobulin monitoring with replacement when levels fall, and ongoing hematologic surveillance.
Patient-reported outcomes from MagnetisMM-3 showed a transient worsening in side-effect-related quality of life domains through the second cycle, consistent with the CRS-concentrated initiation period, followed by recovery and stabilization. Pain and disease symptom scores improved from later cycles onward. By cycle 1, day 15, roughly 40% of patients rated their overall condition as better than at baseline.
Elranatamab's practical advantage over CAR-T therapy is availability. It is off-the-shelf and can be started without the three to four weeks of manufacturing time that CAR-T requires — a meaningful difference when a patient needs rapid disease control. For patients ineligible for CAR-T, or who have relapsed after it, elranatamab provides a way to re-engage anti-myeloma immunity.
Sequencing across BCMA-directed therapies remains the least resolved clinical question. Elranatamab has produced responses in patients previously exposed to BCMA-targeting drugs, but response rates are lower in that population than in BCMA-naïve patients. How much prior BCMA exposure matters likely depends on the type of prior therapy (antibody-drug conjugate, CAR-T, or another bispecific), how deep and durable the prior response was, and how long ago that treatment ended. T cell exhaustion and reduced BCMA surface expression are the two most likely biological contributors to attenuated responses after prior BCMA therapy, though the relative weight of each is not yet defined. For patients in whom BCMA sensitivity appears diminished, bispecific antibodies targeting GPRC5D or FcRH5 offer alternative options.
Key unanswered questions include how elranatamab performs in randomized comparisons with physician's choice regimens, what its long-term survival benefit is as overall survival data mature, whether fixed-duration treatment is feasible in deep responders, and what biomarkers predict who is most likely to benefit or to develop serious infections.
"Synthesis and Evaluation of a Potential RSK2 Degrader in Human Multiple Myeloma Cell Line"
Source
Daisuke Ide, Hidetomo Yokoo, Shinsuke Mizutani, Yu Inoue, Haruya Okamoto, Taku Tsukamoto, Yosuke Demizu, Yuji Shimura, Makoto Oba, Junya Kuroda, Synthesis and Evaluation of a Potential RSK2 Degrader in Human Multiple Myeloma Cell Lines, Chemical and Pharmaceutical Bulletin, 2026, Volume 74, Issue 3, Pages 240-246, Released on J-STAGE March 18, 2026, Online ISSN 1347-5223, Print ISSN 0009-2363, https://doi.org/10.1248/cpb.c25-00731, https://www.jstage.jst.go.jp/article/cpb/74/3/74_c25-00731/_article/-ch…;
Overview
Conventional drugs work by blocking a protein's activity. A newer approach called targeted protein degradation uses the cell's own disposal machinery to eliminate the protein entirely, which can overcome some forms of drug resistance and affect proteins that are difficult to block with traditional inhibitors. This study developed and tested the first degrader compounds targeting RSK2, a signaling enzyme associated with cancer progression, in myeloma cells.
The researchers first evaluated LJH685, an existing RSK2-binding compound, and found it reduced total RSK2 protein levels in myeloma cell lines by engaging the ubiquitin-proteasome system — the cell's primary protein disposal pathway.
They then built four PROTAC compounds based on LJH685. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that simultaneously bind a target protein and an E3 ligase — an enzyme that tags proteins for degradation — bringing them into proximity and triggering destruction of the target. All four PROTACs used pomalidomide as the E3 ligase-binding end, connected to LJH685 by linkers of varying length made from polyethylene glycol units.
All four reduced both total RSK2 and its active phosphorylated form in myeloma cells. The compound with the shortest linker — one PEG unit — showed the strongest degradation activity and anti-proliferative effect, comparable to LJH685 alone. Molecular docking simulations showed that PROTACs with PEG linkers formed stable three-way complexes between RSK2, the PROTAC, and the E3 ligase, while a version without a linker failed to form the correct geometry and showed weaker activity.
The findings establish proof of concept for RSK2 degradation in myeloma cells and identify linker length as a determinant of PROTAC efficacy for this target. The work was conducted in cell models; in vivo studies and clinical testing have not yet been done.
"Multiple myeloma with concomitant chronic lymphocytic leukemia: evidence for independent clonal origin"
Source
Wobst, J., Ruge, H., Senk, S. et al. Multiple myeloma with concomitant chronic lymphocytic leukemia: evidence for independent clonal origin. Leukemia (2026). https://doi.org/10.1038/s41375-026-02918-1 March 18, 2026.
Overview
Multiple myeloma and chronic lymphocytic leukemia (CLL) are both blood cancers that originate from B cells, but at different stages of B cell development. Myeloma arises from plasma cells — the most mature B cell stage — while CLL involves mature B cells that have not completed differentiation into plasma cells. When both cancers occur in the same patient, a question arises: did they develop independently, or do they share a common cell of origin?
Cases of concurrent myeloma and CLL have been reported in the medical literature since the 1960s, but the evidence on whether the two malignancies are clonally related — meaning they descended from the same ancestral cell — has been conflicting. This study examined that question in what the authors describe as the largest published cohort to date, by analyzing the B cell receptor (BCR) sequences in both tumor populations from each patient.
The BCR is a protein unique to each B cell clone, encoded by gene segments that rearrange during B cell development. If myeloma and CLL in the same patient share the same BCR rearrangement, they likely arose from a common precursor. If their BCR sequences differ, they developed independently.
BCR sequencing was performed on plasma cells from bone marrow for the myeloma component and on peripheral blood or CD138-depleted bone marrow fractions for CLL, using validated clinical-grade sequencing kits. Additional genetic analysis included chromosomal copy number testing, IGH translocation assessment by FISH, and targeted sequencing for somatic mutations. One case underwent whole-genome and whole-transcriptome sequencing for deeper characterization.
The methods and patient consent procedures followed standard institutional and ethical requirements. Results from the clonal relationship analysis are reported in the full paper.
"Burden of disease for multiple myeloma in China and the Asia–Pacific region, 1990–2021: a systematic analysis of the Global Burden of Disease (GBD)"
Source
Wang, SX., Luo, T., Yang, N. et al. Burden of disease for multiple myeloma in China and the Asia–Pacific region, 1990–2021: a systematic analysis of the Global Burden of Disease (GBD) 2021 study. Ann Hematol 105, 185 (2026). https://doi.org/10.1007/s00277-026-06923-3 March 18, 2026. 6.
Overview
This study used data from the Global Burden of Disease 2021 database to track myeloma incidence, deaths, and disability-adjusted life years across Asia-Pacific countries from 1990 to 2021, and to project future trends using two forecasting models.
The overall myeloma burden in the region grew substantially over the study period. The increase was most pronounced in China, where age-standardized incidence rose by 919%, deaths by 326%, and disease burden measured in disability-adjusted life years by 622%. Decomposition analysis attributed roughly 60% of the increase in East Asia to population aging rather than changes in underlying disease rates.
Men were more affected than women across the region, with most cases occurring in adults over 70. Higher myeloma rates correlated with higher sociodemographic development index scores across most countries — meaning wealthier, more developed regions had higher reported incidence — with Japan as a notable exception, where the relationship ran in the opposite direction. In lower-income communities, early diagnosis was more commonly documented, though the authors note this may reflect differences in detection practices rather than true disease patterns.
Projections suggest myeloma incidence in China will continue rising, while death rates are expected to stabilize. The gap between male and female disease burden is projected to persist.
The Japan finding — where higher development correlated with lower incidence — is identified as potentially informative for regional prevention planning, though the study does not establish what drives that pattern.
The analysis relies on GBD data, which varies in completeness and quality across countries in the region, and projections based on historical trends may not account for the impact of newer treatments on survival or changes in diagnostic practice
"Multiple Myeloma and Mimicry: Gastrointestinal Tract Histologic Findings in Patients Following Chimeric Antigen Receptor T-cell Therapy and Anti-CD38 Monoclonal Antibodies"
Source
Domenika Ortiz Requena, Elizabeth A. Montgomery, Nemencio R. Ronquillo, Monica Garcia-Buitrago, Rhonda K. Yantiss, Multiple Myeloma and Mimicry: Gastrointestinal Tract Histologic Findings in Patients Following Chimeric Antigen Receptor T-cell Therapy and Anti-CD38 Monoclonal Antibodies, Modern Pathology, 2026, 100991, ISSN 0893-3952, https://doi.org/10.1016/j.modpat.2026.100991. March 19, 2026.
Overview
CAR-T therapy can cause gastrointestinal symptoms months after treatment, but what that injury looks like under the microscope has not been well characterized. This study examined biopsy and surgical specimens from eight patients who developed gastrointestinal symptoms after CAR-T therapy, aiming to identify whether a recognizable tissue pattern exists.
Seven patients had relapsed or refractory myeloma and one had diffuse large B-cell lymphoma. Mean age was 63 years. Diarrhea was the most common symptom, occurring in 88% of patients; nausea or vomiting occurred in 22%. Symptoms developed a mean of 294 days after CAR-T infusion, ranging from 41 to 700 days.
Endoscopic findings varied — some patients had normal-appearing mucosa or mild redness, while others had mucosal granularity and ulcers in both the upper and lower gastrointestinal tract. Infection was ruled out in the five patients tested; one had enteropathogenic E. coli, but no viral pathogens were identified on immunohistochemistry. None of the patients had taken medications known to cause gastrointestinal injury in the three months before endoscopy.
Across all 43 mucosal biopsy sets and three surgical specimens, a consistent tissue pattern emerged. The crypts and glands — particularly in the deeper layers of the mucosa — showed regenerative changes and cells with reduced cytoplasm. Apoptotic epithelial cells and increased lymphocytes within the epithelium were present in every case. The surrounding connective tissue was largely quiet, with few inflammatory cells and notably absent or reduced plasma cells.
The authors propose that this combination of features — epithelial apoptosis, intraepithelial lymphocytosis, and deep mucosal involvement with minimal surrounding inflammation — represents a recognizable pattern of CAR-T-associated gastrointestinal injury. Identifying it may help pathologists flag the possibility of CAR-T-related injury when reviewing biopsies from patients with a relevant treatment history.
"Enhancing antitumour response to proteasome inhibitors with inhibitors of insulin-degrading enzyme, a new molecular vulnerability in multiple myeloma"
Source
Lesire, L., Deprez-Poulain, R., Bosc, D., Leroux, F., Landry, V., Ourabah, S., Tardy, M., Maillard, C., Gealageas, R., Dumont, J., Herledan, A., Warenghem, S., Cruette, M., Lenglart, C., Biela, A., Piveteau, C., De Smedt, E., Muylaert, C., Liang, W., … Deprez, B. (2026). Enhancing antitumour response to proteasome inhibitors with inhibitors of insulin-degrading enzyme, a new molecular vulnerability in multiple myeloma. British Journal of Pharmacology, 1–22. https://doi.org/10.1111/bph.70407 March 19, 2026.
Overview
CAR-T therapy can cause gastrointestinal symptoms months after treatment, but what that injury looks like under the microscope Resistance to proteasome inhibitors is a common problem in myeloma, and identifying ways to restore their effectiveness is an active area of research. This study investigated whether blocking an enzyme called IDE (insulin-degrading enzyme) could make myeloma cells more sensitive to proteasome inhibitors.
The researchers first examined gene expression data from myeloma patients and found that lower IDE expression correlated with longer overall survival — suggesting IDE activity may support myeloma cell survival.
They then developed novel IDE inhibitor compounds and confirmed using X-ray crystallography and enzymatic assays that these compounds bind IDE with high affinity. When myeloma cell lines and primary myeloma cells from newly diagnosed and relapsed patients were treated with IDE inhibitors at concentrations that fully blocked IDE activity, the cells became more sensitive to proteasome inhibitors. The combination reduced levels of c-Myc — a protein that drives cell proliferation — and activated two stress response pathways: the integrated stress response and the DNA damage response. Together, those changes increased cell death in myeloma cells that were resistant to proteasome inhibitors alone.
Importantly, the combination did not appear to harm the non-myeloma cells in the surrounding bone marrow environment, suggesting some selectivity for tumor cells.
The results were confirmed in a mouse model of myeloma using an optimized IDE inhibitor combined with bortezomib. The combination outperformed bortezomib alone in that immunocompetent animal model.
The findings identify IDE as a candidate therapeutic target in proteasome inhibitor-resistant myeloma and provide preclinical evidence that IDE inhibitors could be used alongside proteasome inhibitors to restore drug sensitivity. Clinical testing has not yet been conducted.
"Impact of Pre-Transplant Depth of Response on Outcomes in Patients With Multiple Myeloma: A Report on Behalf of Pakistan Blood and Marrow Transplant Group"
Source
N.Ali, D.Ahmed, R.Iftikhar, et al. “Impact of Pre-Transplant Depth of Response on Outcomes in Patients With Multiple Myeloma: A Report on Behalf of Pakistan Blood and Marrow Transplant Group.” Asia-Pacific Journal of Clinical Oncology (2026): . https://doi.org/10.1111/ajco.70104 March 20, 2026.
Overview
How well myeloma responds to induction chemotherapy before a stem cell transplant has been linked to how long patients stay in remission afterward. This retrospective study examined that relationship across six transplant centers in Pakistan over 18 years, in a setting where resources and treatment access differ from high-income countries where most of the existing evidence originates.
The analysis included 223 patients with a mean age of 49 years; 70% were male. Back pain was the most common presenting symptom (56%), followed by pathological fractures (15%). Anemia was present in 45% and kidney impairment in 26%. IgG kappa was the most common myeloma protein subtype. By ISS staging, 33% had stage I, 27% stage II, and 38% stage III disease. Induction therapy was RVd in 42% of patients and CyBorD in 41%.
After induction, 7% achieved stringent complete response, 22% complete response, 19% very good partial response, and 18% partial response. By the time of transplant, 58% had achieved complete response or better and 20% had achieved very good partial response.
Patients who went to transplant in complete response or stringent complete response had significantly better overall survival and disease-free survival than those with lesser responses. Age under 50 and achieving at least very good partial response before transplant were also independently associated with better outcomes. Median overall survival was 72 months and median disease-free survival was 47 months across the full cohort.
The findings are consistent with data from higher-income settings and support prioritizing treatment intensity during induction to achieve the deepest possible response before transplant, even where newer drug combinations are less accessible. The retrospective design and variation in practice across six centers over 18 years limit precision, but the consistency of the response-depth finding with established evidence strengthens its interpretation.
"The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma"
Source
S.Barachini, R.Cassano Cassano, F.Ronca, I.Petrini, S.Galimberti, and G.Buda, “The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma,” European Journal of Haematology (2026): 1–19, https://doi.org/10.1111/ejh.70168. March 19, 2026.
Overview
Bispecific antibodies and CAR-T therapy have produced deep responses in relapsed and refractory myeloma, but many patients eventually relapse. This review examined why the environment surrounding myeloma cells in the bone marrow — called the tumor microenvironment — limits how well bispecific antibodies work, and what combination strategies are being developed to address that.
Bispecific antibodies work by grabbing a T cell with one arm and a myeloma cell with the other, forcing the T cell to kill the cancer cell. That mechanism depends on T cells being functional and present in sufficient numbers. The bone marrow in myeloma is not neutral territory — it contains cell types and chemical signals that actively suppress T cell activity. Regulatory T cells and myeloid-derived suppressor cells dampen immune responses. Stromal cells produce cytokines including IL-6 and TGF-β that impair T cell activation. Low oxygen levels and metabolic competition within the marrow further reduce T cell effectiveness.
A separate problem is T cell exhaustion. When T cells are continuously stimulated by CD3-engaging bispecific antibodies without adequate co-stimulation, they can enter a dysfunctional state in which they stop responding effectively — a recognized cause of relapse after initial response.
Myeloma cells can also reduce or eliminate the surface proteins that bispecific antibodies target, a process called antigen escape. When BCMA expression falls on myeloma cells, BCMA-targeting bispecific antibodies lose their grip.
Several strategies are in development to address these barriers. Trispecific antibodies add a third binding arm to the construct. One approach co-engages CD28 alongside CD3, providing a co-stimulatory signal that reduces T cell exhaustion. Another targets two myeloma antigens simultaneously — such as BCMA and GPRC5D — to reduce the chance that antigen loss in one pathway allows the cancer to escape entirely. A compound called HPN217 adds an albumin-binding domain to extend the drug's half-life in the blood.
Combinations pairing bispecific antibodies with immunomodulatory drugs such as iberdomide, or with checkpoint inhibitors that remove suppressive signals on T cells, are being tested in trials including MonumenTAL-3, which is evaluating talquetamab combined with daratumumab with or without pomalidomide.
The central argument of the review is that bispecific antibody efficacy cannot be understood or optimized by looking at the drug alone — the immune environment the drug operates in shapes its effects as much as the drug's intrinsic properties. Improving outcomes will require reshaping that environment alongside deploying more sophisticated antibody constructs.
"On-target, off-tumor oral toxicities of talquetamab in heavily pretreated multiple myeloma"
Source
Alves, F.A., Perez Perez, A., Jaguar, G.C. et al. On-target, off-tumor oral toxicities of talquetamab in heavily pretreated multiple myeloma. Support Care Cancer 34, 347 (2026). https://doi.org/10.1007/s00520-026-10583-4 March 20, 2026.
Overview
Talquetamab is a bispecific antibody that targets a protein called GPRC5D on myeloma cells alongside CD3 on T cells. It produces responses in roughly 70% of heavily pretreated patients, but it causes a distinct set of side effects in the mouth, tongue, and salivary glands that are not seen with other bispecific antibodies. This review summarized the published evidence on those toxicities, including how common they are, when they appear, and how they are managed.
GPRC5D is expressed not only on myeloma cells but also on epithelial cells in the tongue, salivary glands, and other keratinized tissues in the mouth. When talquetamab activates T cells against myeloma cells, those same T cells can attack these normal oral tissues — an on-target but off-tumor effect.
In the MonumenTAL-1 trial, taste disturbance (dysgeusia) occurred in up to 72% of patients, dry mouth in 39%, and difficulty swallowing in 24%. These effects typically began within the first few weeks of treatment and tended to persist rather than resolve. The functional consequences are not trivial — impaired taste and dry mouth reduce the desire and ability to eat, and weight loss exceeding 6% of baseline body weight was commonly reported.
Current management is supportive: steroid mouthwashes, saliva substitutes or stimulants, nutritional counseling, and dose reductions or delays when toxicity is severe. None of these approaches have shown strong efficacy in resolving the underlying problem. The TALISMAN trial is prospectively evaluating whether prophylactic dexamethasone mouthwash and pregabalin can prevent or reduce oral toxicities before they develop.
Early identification of these side effects and involvement of dietitians and dental or oral medicine specialists alongside the oncology team appears important for maintaining nutrition and treatment continuity in patients on talquetamab.
"Efficacy of stem cell boost (SCB) for chimeric antigen receptor-T cell therapy (CAR-T)-related hematologic toxicity in patients with relapsed/refractory multiple myeloma (RRMM)—real world experience from the US multiple myeloma immunotherapy consortium"
Source
Varga, C., Robinson, M., Davis, J.A. et al. Efficacy of stem cell boost (SCB) for chimeric antigen receptor-T cell therapy (CAR-T)-related hematologic toxicity in patients with relapsed/refractory multiple myeloma (RRMM)—real world experience from the US multiple myeloma immunotherapy consortium. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01469-z March 20, 2026.
Overview
Low blood counts lasting weeks or months after CAR-T infusion — called prolonged cytopenias — affect a meaningful proportion of patients and can cause serious complications. One approach to accelerating blood count recovery is to infuse previously collected stem cells, a procedure called a stem cell boost (SCB). This retrospective multi-center study compared outcomes in patients who received a stem cell boost for prolonged cytopenias after CAR-T therapy against matched patients managed with supportive care alone.
Of 590 CAR-T recipients reviewed across participating centers between June 2021 and March 2024, 91 (15%) developed prolonged cytopenias. 39 of those received a stem cell boost. The comparison group was selected from the remaining patients by matching on cytopenia severity at the 75th percentile threshold for the stem cell boost cohort.
The median CD34+ cell dose infused was 2.9 million cells per kilogram, given at a median of 53 days after CAR-T infusion. 97% of patients who received the boost achieved hematologic recovery, with a median time to recovery of 24 days. No new toxicities attributable to the stem cell boost were observed.
At day 90 after CAR-T infusion, patients who had received the boost had higher median hemoglobin (10.6 versus 8.7 g/dL) and higher median platelet counts (135 versus 35 × 10³/µL) than matched controls, both differences statistically significant.
Median progression-free survival was 11.0 months in the stem cell boost group and 8.2 months in the comparison group. Median overall survival was not reached in the boost group versus 12.3 months in the comparison group, though these comparisons should be interpreted cautiously given the non-randomized design and potential for selection differences between groups.
The findings support stem cell boost as a safe and effective intervention for prolonged cytopenias after CAR-T, with rapid recovery in nearly all patients and no apparent compromise of CAR-T efficacy.
"Advancing multiple myeloma therapy: A systematic analysis of corticosteroids and monoclonal antibodies as dual therapeutic agents"
Source
Alam F, Siddiqui H, Nihal A, Andleeb M, Zaman AQU, Khushk MI, Hussain F, Rai R, Fatima FB, Kumar D, Rizvi SAFA, Jabeen S, Jawed I, Qadir U, Zakeri MA. Advancing multiple myeloma therapy: A systematic analysis of corticosteroids and monoclonal antibodies as dual therapeutic agents. World J Methodol 2026; 16(1): 107864 [DOI: 10.5662/wjm.v16.i1.107864] March 20, 2026.
Overview
Low blood counts lasting weeks or months after CAR-T infusion — called prolonged cytopenias — affect a meaningful proportion of patients and can cause serious complications. One approach to accelerating blood count recovery is to infuse previously collected stem cells, a procedure called a stem cell boost (SCB). This retrospective multi-center study compared outcomes in patients who received a stem cell boost for prolonged cytopenias after CAR-T therapy against matched patients managed with supportive care alone.
Of 590 CAR-T recipients reviewed across participating centers between June 2021 and March 2024, 91 (15%) developed prolonged cytopenias. 39 of those received a stem cell boost. The comparison group was selected from the remaining patients by matching on cytopenia severity at the 75th percentile threshold for the stem cell boost cohort.
The median CD34+ cell dose infused was 2.9 million cells per kilogram, given at a median of 53 days after CAR-T infusion. 97% of patients who received the boost achieved hematologic recovery, with a median time to recovery of 24 days. No new toxicities attributable to the stem cell boost were observed.
At day 90 after CAR-T infusion, patients who had received the boost had higher median hemoglobin (10.6 versus 8.7 g/dL) and higher median platelet counts (135 versus 35 × 10³/µL) than matched controls, both differences statistically significant.
Median progression-free survival was 11.0 months in the stem cell boost group and 8.2 months in the comparison group. Median overall survival was not reached in the boost group versus 12.3 months in the comparison group, though these comparisons should be interpreted cautiously given the non-randomized design and potential for selection differences between groups.
The findings support stem cell boost as a safe and effective intervention for prolonged cytopenias after CAR-T, with rapid recovery in nearly all patients and no apparent compromise of CAR-T efficacy.
"Steady-state mobilization with on-demand plerixafor after CD38 antibody-based induction in multiple myeloma patients"
Source
Röhnert MA, Seifert A, Trautmann-Grill K, Röllig C, Zimmer K, Egger-Heidrich K, et al. Steady-state mobilization with on-demand plerixafor after CD38 antibody-based induction in multiple myeloma patients. Transfusion. 2026. https://doi.org/10.1111/trf.70165 March 20, 2026.
Overview
Autologous stem cell transplant remains standard treatment for fit, newly diagnosed myeloma patients. Before transplant, stem cells must be collected from the patient's blood — a process called mobilization and apheresis. The widespread adoption of four-drug induction regimens that include daratumumab has raised questions about whether daratumumab impairs stem cell collection.
This retrospective single-center study compared stem cell mobilization outcomes in 85 patients who received daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) against 68 patients who received bortezomib, cyclophosphamide, and dexamethasone (VCd).
Dara-VTd produced deeper responses — 81% of patients achieved very good partial response or better, compared to 42% with VCd. Despite that, stem cell mobilization was substantially more difficult in the Dara-VTd group. CD34+ cell counts in the blood before the first apheresis session were lower (16 versus 50 cells/µL after adjusting for plerixafor use), and 64% of Dara-VTd patients required plerixafor — a drug that forces stem cells out of the bone marrow — compared to 15% in the VCd group.
With plerixafor used on demand when mobilization was poor, final stem cell yields were comparable between the two groups (6.4 versus 6.0 × 10⁶ CD34+ cells/kg), and target collection was achieved in 90% of Dara-VTd patients and 94% of VCd patients. In multivariate analysis, Dara-VTd induction, prior radiation, and higher tumor burden were independent predictors of mobilization difficulty.
A secondary observation was that a high proportion of collected stem cells went unused in both groups — a finding that may be relevant for planning how many cells to collect and store.
The results indicate that daratumumab-based induction impairs mobilization kinetics but that adequate stem cell collection remains achievable when plerixafor is used reactively in patients who mobilize poorly.
"Cost-Effectiveness of Maintaining Higher Stem-Cell Collection Thresholds in the Chimeric Antigen Receptor T-Cell Era for Multiple Myeloma"
Source
Ehsan Malek et al. Cost-Effectiveness of Maintaining Higher Stem-Cell Collection Thresholds in the Chimeric Antigen Receptor T-Cell Era for Multiple Myeloma. JCO Clin Cancer Inform 10, e2500308(2026). DOI:10.1200/CCI-25-00308 March 20, 2026.
Overview
Prolonged low blood counts after CAR-T therapy increase the risk of serious infection. Having a stored supply of the patient's own stem cells available to infuse if counts fail to recover — called a stem cell boost — can accelerate blood count recovery. But collecting and storing those cells adds cost and procedural burden upfront, and not every patient will need them. This study used a mathematical model to estimate whether routinely collecting stem cells before CAR-T therapy is economically justified.
Researchers built a Markov model simulating 10,000 patients undergoing CAR-T therapy over eight years, comparing two strategies: no stem cell collection versus universal proactive collection with a boost available for patients who develop prolonged cytopenias. Transition probabilities for neutropenia, infection, and infection-related death were drawn from the CARTITUDE-4 trial and published stem cell boost data.
Universal reserve collection reduced severe infections from approximately 650 to approximately 260 per 10,000 patients and prevented roughly 50 infection-related deaths. However, the per-patient cost was substantially higher in the collection arm — approximately $19,700 versus $4,500 — driven primarily by the upfront collection cost of roughly $18,000 per patient. Long-term survival was similar between strategies, as relapse-related mortality dominated outcomes over the full model horizon and was not affected by the stem cell boost.
Sensitivity analysis identified hospitalization cost and stem cell collection cost as the variables that most influenced the results.
The model suggests that universal proactive collection is not cost-effective when applied to all CAR-T recipients. A risk-adapted approach — collecting stem cells only in patients identified as most likely to develop prolonged cytopenias — would reduce unnecessary collection costs while preserving benefit for those at highest risk. Defining that high-risk group precisely enough to make selective collection practical remains an open question.
"Diagnostic brain-to-liver [18f]fdg uptake ratio predicts survival in multiple myeloma: A retrospective study"
Source
Takahashi, M.E.S., dos Santos, T.P., Cralcev, C. et al. Diagnostic brain-to-liver [18f]fdg uptake ratio predicts survival in multiple myeloma: A retrospective study. Eur J Nucl Med Mol Imaging (2026). https://doi.org/10.1007/s00259-026-07844-z March 21, 2026.
Overview
PET/CT scans measure how much radioactive glucose a tissue absorbs, reflecting its metabolic activity. In several cancers, the brain shows reduced glucose uptake relative to normal — thought to reflect competition for glucose between tumor cells and normal tissues, a phenomenon linked to high lactate production by cancer cells. This study tested whether the ratio of brain to liver glucose uptake on a diagnostic PET/CT scan carries prognostic information in myeloma.
Researchers retrospectively analyzed PET/CT scans from 72 newly diagnosed myeloma patients (58% male, median age 65 years, 67% ISS stage III). The brain-to-liver ratio (BLR) was calculated by dividing the mean standardized uptake value of the whole brain by that of the liver — both measurements routinely available from standard PET/CT acquisitions.
BLR correlated with established markers of disease burden. It differed significantly by sex and body weight status, and inversely correlated with beta-2 microglobulin levels — a standard marker of tumor burden — with a correlation coefficient of −0.42.
At a median follow-up of 23 months, 74% of patients had died from myeloma-related causes. Patients with a BLR above 2.7 had substantially better outcomes: 60-month overall survival was 52% versus 10%, and 60-month progression-free survival was 19% versus 3%. In multivariate Cox regression, BLR remained an independent predictor of both overall and progression-free survival after accounting for ISS stage and transplant use, with hazard ratios of 1.86 and 1.93 respectively.
The BLR requires no additional imaging or blood tests beyond what is already collected at diagnosis. Whether it adds clinically actionable information beyond standard risk factors, and whether the threshold of 2.7 holds in larger prospective cohorts, would need further validation.
"Efficacy and Tolerability of Weekly Bortezomib, Lenalidomide, and Dexamethasone Protocols in Transplant-Ineligible Newly Diagnosed Myeloma: An Australian Real-World, Multicenter Study"
Source
S.Kurniawan, A.Hwang, N. W.Doo, et al. “Efficacy and Tolerability of Weekly Bortezomib, Lenalidomide, and Dexamethasone Protocols in Transplant-Ineligible Newly Diagnosed Myeloma: An Australian Real-World, Multicenter Study.” Asia-Pacific Journal of Clinical Oncology (2026): . https://doi.org/10.1111/ajco.70101 March 22, 2026.
Overview
Bortezomib, lenalidomide, and dexamethasone (RVD) is widely used as initial treatment for myeloma, but the twice-weekly bortezomib schedule used in pivotal clinical trials produces substantial toxicity, particularly in older or frailer patients who are not candidates for stem cell transplant. Weekly bortezomib is used in practice to reduce that burden, but prospective data on how modified weekly schedules perform outside of trials are limited. This study reported outcomes from 83 transplant-ineligible newly diagnosed myeloma patients treated at six Australian hospitals with one of two weekly bortezomib RVD schedules — Modified SWOG and Modified RVD Lite — adapted from their corresponding trials.
At a median follow-up of 27.4 months, both regimens produced high response rates. Modified SWOG achieved an overall response rate of 91%, with 71% reaching very good partial response or better and a 24-month progression-free survival of 63%. Modified RVD Lite achieved a 94% overall response rate, 65% reaching very good partial response or better, and a 24-month progression-free survival of 54%.
Despite the shift to weekly dosing and dose attenuation in practice, toxicity remained substantial. 48% of patients required hospitalization and 31% stopped treatment early due to side effects. Peripheral neuropathy occurred in 39% of patients overall, but severe neuropathy (grade 3) was seen in only two patients — lower than rates reported in trials using twice-weekly bortezomib.
The findings suggest that weekly RVD schedules produce efficacy comparable to twice-weekly regimens reported in trials, while reducing severe neuropathy. However, the overall toxicity burden in this older, transplant-ineligible population remains considerable, with nearly one in three patients unable to complete planned treatment.
"FTO–CHRM3 axis regulates multiple myeloma progression: a machine learning-based identification"
Source
Lu, B., Bin, T., Deng, XF. et al. FTO–CHRM3 axis regulates multiple myeloma progression: a machine learning-based identification. Ann Hematol 105, 201 (2026). https://doi.org/10.1007/s00277-026-06940-2 March 23, 2026.
Overview
FTO is an enzyme that removes a chemical modification called m6A from RNA, altering how genes are expressed. It has been associated with cancer progression in several tumor types, but its role in myeloma has not been well characterized. This study used machine learning, gene expression analysis, and single-cell sequencing to identify which genes work alongside FTO in myeloma and what biological processes they affect.
FTO was expressed at higher levels in myeloma tissue than in normal tissue, and higher expression correlated with worse prognosis. Machine learning and correlation analysis identified four genes with expression patterns consistently linked to FTO in myeloma: CHRM3, GINS3, RRM2, and SHCBP1. Immunohistochemical staining of myeloma tissue confirmed the correlation between FTO and CHRM3 expression, focusing subsequent analysis on that pair.
Pathway analysis showed that FTO and CHRM3 were both associated with DNA replication and cell cycle regulation — processes that support tumor cell proliferation. Immune infiltration analysis found that myeloma samples with high FTO and CHRM3 expression had altered levels of two immune cell types: M2 macrophages and eosinophils. M2 macrophages are generally associated with an immunosuppressive tumor environment, though the functional significance of the eosinophil finding was not fully characterized.
Single-cell RNA sequencing identified a gene called SLC8A1, involved in calcium signaling, as specifically expressed in monocytes within the myeloma microenvironment in high-FTO cases.
The authors propose that FTO promotes myeloma progression partly through CHRM3 and dysregulation of calcium signaling. The work was conducted through data analysis and tissue staining; functional experiments in cell or animal models would be needed to establish causal relationships before these targets could be considered for therapeutic development.
"External Validation of Predictive Models for Infection in Patients With Newly Diagnosed Multiple Myeloma"
Source
Daniel Andrés Ribero-Vargas, Juan Camilo Jaramillo-Álvarez, José C Álvarez-Payares, Juan Carlos Hernández-Rodríguez, Roberto Mario Cárdenas-Ramos, Daniela Vélez-Henao, Carlos José Atencia-Flórez, EXTERNAL VALIDATION OF PREDICTIVE MODELS FOR INFECTION IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA, Blood Global Hematology, 2026, 100087, ISSN 3050-5658, https://doi.org/10.1016/j.bglo.2026.100087. March 23, 2026.
Overview
Serious infections are common in the weeks after a myeloma diagnosis, before treatment has had time to work and while the immune system is most compromised. Several scoring models have been developed to identify which patients are at highest risk, but most were built and tested in populations from Europe or North America. This study tested four of those models in 321 newly diagnosed myeloma patients from three hospitals in Medellín, Colombia, between 2012 and 2021.
52% of patients developed a grade 3 or higher infection within 90 days of diagnosis — a higher rate than typically reported in clinical trial populations, likely reflecting the real-world severity of disease at presentation and limited prophylaxis use. 75% of infections were healthcare-associated. Pneumonia was most common (30%), followed by bloodstream infections (29%) and urinary tract infections (24%). The most frequently isolated organisms were Staphylococcus aureus (27%), Escherichia coli (22%), and Klebsiella pneumoniae (18%), with gram-negative bacteria accounting for 54% of isolates overall. TMP/SMX resistance was present in 40% of isolates and quinolone resistance in 12% — findings relevant to prophylaxis choices in this setting. Only 11% of patients received antibiotic prophylaxis. Median time from diagnosis to first infection was 15 days.
Of the four models validated, a combined model performed best (AUC 0.70), followed by the FIRST and IRMM models (AUC 0.67 each). Four variables were independently associated with infection risk: LDH at or above 200 U/L (odds ratio 2.62), albumin at or below 3 g/dL (OR 1.91), diabetes mellitus (OR 2.69), and beta-2 microglobulin at or above 6 mg/L (OR 1.68).
"Predictors of 30-day readmissions post-CAR-T in patients with relapsed/refractory multiple myeloma using the United States nationwide readmission database"
Source
Shah, R., Vojjala, N., Cheng, T. et al. Predictors of 30-day readmissions post-CAR-T in patients with relapsed/refractory multiple myeloma using the United States nationwide readmission database. Ann Hematol 105, 198 (2026). https://doi.org/10.1007/s00277-026-06927-z March 23, 2026.
Overview
BCMA-directed CAR-T therapy produces high response rates in relapsed and refractory myeloma, but the period after hospital discharge carries substantial risk. This retrospective study used the US National Readmission Database to examine 30-day readmission rates, causes, and predictors in 1,180 myeloma patients who received ide-cel or cilta-cel at hospitals across the United States between January 2021 and November 2022.
82% received ide-cel and 18% cilta-cel. Mean age was 63 years; 62% were male. 80% were treated at large urban teaching hospitals. Medicare was the primary insurer for 51% of patients.
During the initial hospitalization, 68% developed cytokine release syndrome, though only 5% required tocilizumab. ICANS occurred in 8% overall — 7% in ide-cel recipients and 9% in cilta-cel recipients. Neutropenia developed in 38% of patients. Sepsis occurred in 4% and septic shock in 2%. Mean length of stay was 14 days for ide-cel and 16 days for cilta-cel. In-hospital mortality was 2.3% for ide-cel and 3.6% for cilta-cel.
Of 1,155 patients discharged alive, 226 (17%) were readmitted within 30 days. Readmission rates did not differ significantly between the two CAR-T products (16% versus 18%). Immune effector complications were the most common cause of readmission (33%), followed by infections (17%). Mean length of stay during readmission was 6.5 days, with 7% mortality during the readmission hospitalization. Mean hospital charges for readmission were $105,390.
In multivariate analysis, three factors were associated with significantly higher readmission risk: hemophagocytic lymphohistiocytosis during the index admission (hazard ratio 3.42), mechanical ventilation during the index admission (HR 11.30), and treatment at a non-metropolitan hospital (HR 4.77). Patients who developed CRS during the index admission had lower readmission rates (HR 0.46), which the authors suggest may reflect more intensive post-discharge monitoring in that group. Standard comorbidities — diabetes, kidney disease, cardiovascular disease — did not predict readmission, suggesting treatment-related factors outweigh baseline health status in driving early returns to hospital.
"Real-world effectiveness of bortezomib maintenance following VMP induction in transplant-ineligible multiple myeloma: a target trial emulation study"
Source
Lee, J.Y., Choi, S., Jung, S. et al. Real-world effectiveness of bortezomib maintenance following VMP induction in transplant-ineligible multiple myeloma: a target trial emulation study. Ann Hematol 105, 193 (2026). https://doi.org/10.1007/s00277-026-06849-w March 23, 2026.
Overview
For patients with myeloma who are not candidates for stem cell transplant, bortezomib combined with melphalan and prednisone (VMP) is an established induction regimen. Whether continuing bortezomib as maintenance therapy after completing VMP improves outcomes is less well established. This study used target trial emulation — a method that applies clinical trial logic to observational data — to compare bortezomib maintenance against no maintenance following VMP.
The maintenance cohort came from a prospective Korean study (KMMWP-174) and the control cohort from a multicenter registry. Eligible patients had completed nine VMP cycles, achieved at least a partial response, and remained progression-free for 60 days. After propensity score matching, 54 patients per group were analyzed.
Median progression-free survival was 26.5 months with bortezomib maintenance versus 8.8 months without it — a hazard ratio of 0.44, indicating patients on maintenance had less than half the risk of progression or death at any given time point. The benefit was consistent across subgroups including patients aged 70 and older, those with ISS stage II or III disease, and those with high-risk cytogenetics. Overall survival showed a trend favoring maintenance (HR 0.70) that did not reach statistical significance.
Grade 3 or higher adverse events occurred in 19% of the maintenance group and 31% of the control group. No grade 3 or higher peripheral neuropathy was observed in either group.
The non-randomized design is the primary limitation, and the E-value sensitivity analysis conducted by the authors provides some reassurance about unmeasured confounding but cannot eliminate it. The findings support bortezomib maintenance as a reasonable post-VMP strategy in transplant-ineligible patients, particularly older adults in settings where VMP remains a primary induction option and newer quadruplet regimens are less accessible.
"Dynamic Cytogenetic Evolution in Multiple Myeloma: Prognostic Implications from Diagnosis to First Relapse"
Source
Qi Chen, Tian Tian, Yu Shi, Xuxing Shen, Hairong Qiu, Yuanyuan Jin, Lijuan Chen, Rui Guo, Dynamic Cytogenetic Evolution in Multiple Myeloma: Prognostic Implications from Diagnosis to First Relapse, The Oncologist, 2026;, oyag105, https://doi.org/10.1093/oncolo/oyag105 March 23, 2026. .
Overview
Myeloma's genetic profile is not fixed at diagnosis. As the disease progresses and responds to treatment, the mix of chromosomal abnormalities in tumor cells can shift — new abnormalities can appear and existing ones can become more prevalent. This study tracked those changes in 106 myeloma patients in China, comparing chromosomal findings at diagnosis with those at first relapse using a technique called cIg-FISH, which identifies specific chromosomal changes in individual plasma cells.
At first relapse, 33% of patients had acquired at least one new chromosomal abnormality not present at diagnosis. Two abnormalities became significantly more common at relapse: extra copies of chromosome 1q21 (1q21+) and deletion of chromosome 17p13 (del(17p13)), both of which are associated with high-risk disease. Among patients with 1q21+, the proportion with amplification — defined as four or more copies rather than three — grew from 27% at diagnosis to 41% at relapse, while the lower-level gain remained stable.
The prognostic implications differed depending on when and how 1q21+ was detected. Amplification at diagnosis predicted shorter first progression-free survival. Gain (three copies) at relapse correlated with shorter second progression-free survival, particularly when it co-occurred with del(17p13), which happened in 28% of those cases. Both persistent 1q21+ and newly acquired del(17p13) at relapse were associated with shorter overall survival.
Clonal dynamics also carried prognostic weight independently of which specific abnormality was present. Patients whose abnormal clone expanded by more than 20% between diagnosis and relapse had shorter first progression-free survival than those with stable clone size. Patients who acquired new abnormalities at relapse had shorter second progression-free survival and a trend toward worse overall survival.
The findings support repeating chromosomal testing at relapse rather than relying solely on the diagnosis result, as the genetic risk profile can change in ways that affect treatment planning.
"Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma"
Source
Lu, P., Shangguan, W., Qian, W. et al. Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma. Cell Death Dis (2026). https://doi.org/10.1038/s41419-026-08591-7 March 23, 2026.
Overview
KDM5C is an enzyme known for removing methyl groups from histone proteins — a modification that normally represses gene activity. This study found that KDM5C contributes to bortezomib resistance in myeloma through a completely different mechanism, one that does not involve its demethylase activity.
KDM5C was expressed at higher levels in myeloma cells from patients who had become resistant to bortezomib and in those with relapsed disease. Higher KDM5C expression correlated with shorter overall survival. When the researchers reduced KDM5C levels in myeloma cells, the cells became more sensitive to bortezomib in both cell culture and animal models.
The mechanism involves KDM5C forming a protein complex with two other molecules — CBP and MYC — through a structural domain called PHD2. This complex does not affect the histone methylation marks that KDM5C normally regulates. Instead, it promotes acetylation of histone H3 at lysine 27 (H3K27ac), a modification associated with active gene expression, specifically at the promoter region of a gene called PERK. This activates PERK transcription, which in turn promotes phosphorylation of a protein called Nrf2, strengthening the unfolded protein response — a stress-management pathway that myeloma cells depend on to survive proteasome inhibitor treatment. The histone methylation marks at the same PERK promoter region were unaffected, confirming the effect is independent of KDM5C's canonical demethylase function.
The findings identify a non-canonical role for KDM5C in sustaining the stress response that allows myeloma cells to tolerate proteasome inhibition. Targeting KDM5C or disrupting the KDM5C-CBP-MYC complex represents a potential strategy for overcoming bortezomib resistance, though clinical studies have not yet been conducted.
"Circulating levels of insulin-like growth factor I (IGF-I) and risk of multiple myeloma: An observational and Mendelian randomisation study"
Source
Benavente Y, Hermosa S, Papadimitriou N, Clay-Gilmour A, Brown EE, Hofmann JN, et al. Circulating levels of insulin-like growth factor I (IGF-I) and risk of multiple myeloma: An observational and Mendelian randomisation study. Br J Haematol. 2026;00:1–12. https://doi.org/10.1111/bjh.70444 March 23, 2026.
Overview
Insulin-like growth factor I (IGF-I) is a hormone that promotes cell growth and has been implicated in several cancers, but its relationship to myeloma has been inconsistent across studies. This analysis combined two approaches to examine whether IGF-I levels influence myeloma risk: a prospective analysis of blood samples from UK Biobank participants, and a Mendelian randomization analysis using genetic data from the InterLymph consortium.
The UK Biobank analysis included 444,187 participants, of whom 732 developed myeloma during follow-up. Each one standard deviation increase in circulating IGF-I at baseline was associated with an 11% higher risk of myeloma (HR 1.11, 95% CI 1.01–1.22). The association was stronger in the years immediately before diagnosis, which may reflect early disease effects on IGF-I levels rather than a purely causal relationship running in the other direction.
Mendelian randomization uses genetic variants that predict IGF-I levels as a natural experiment, reducing the influence of confounding and reverse causation. In the InterLymph dataset of 2,434 myeloma cases and 2,567 controls, genetically predicted higher IGF-I was associated with a 27% higher myeloma risk (OR 1.27, 95% CI 1.05–1.54). This association was specific to myeloma — genetically predicted IGF-I levels were not associated with any other lymphoid malignancy examined. Genetically predicted IGFBP-3 levels, which modulate IGF-I bioavailability, showed no association with any lymphoid cancer.
A secondary finding replicated prior evidence linking IGF-I to chronic lymphocytic leukemia in obese men, where the association was stronger than in the general population.
The convergence of the observational and genetic analyses points toward IGF-I as a contributor to myeloma susceptibility rather than simply a marker of early disease, though the mechanism by which IGF-I may promote myeloma development warrants further investigation.
"CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target"
Source
Forster, S., Reinhardt, C., Boy, M. et al. CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target. Leukemia (2026). https://doi.org/10.1038/s41375-026-02899-1 March 23, 2026.
Overview
As myeloma progresses and becomes resistant to treatment, it sometimes spreads outside the bone marrow — a pattern called extramedullary disease that is associated with particularly poor outcomes. This study identified a surface protein called CD70 as a contributor to that progression.
CD70 expression on myeloma cells was an independent predictor of shorter overall survival in patient data. The researchers found that CD70 activates its receptor CD27 on the same or neighboring myeloma cells, triggering two downstream signaling pathways — MAPK/ERK and Wnt — that promote cell division and proliferation. This was demonstrated in both myeloma cell lines and primary cells taken directly from patients. As a result of this proliferative advantage, CD70 expression increased at advanced disease stages and was particularly elevated in extramedullary myeloma.
When the researchers blocked CD70/CD27 signaling — either by deleting CD70 from myeloma cells using gene editing or by using blocking antibodies — tumor growth was completely abolished in mouse xenograft models. They also tested cusatuzumab, an antibody engineered to enhance immune-mediated killing (ADCC-enhanced), and found it produced strong anti-myeloma activity in the same models.
The findings identify CD70 as a driver of myeloma proliferation rather than just a marker of advanced disease, and suggest that blocking CD70 — through antibodies that either neutralize the signaling or recruit immune effectors to kill CD70-expressing cells — may be effective in patients whose disease has progressed to extramedullary stages. Clinical testing of this approach has not yet been reported.
"Body composition predicts poor outcomes and reveals immunometabolic dysfunction via single-cell profiling in anti-BCMA CAR T-treated myeloma"
Source
Wiemers, T.C., Rade, M., Grieb, N., Ferle, M., Dermendzhiev, T., Fandrei, D., Born, P., Fischer, L., Seiffert, S., Grahnert, A., Friedrich, M., Baber, R., Kreuz, M., Metzeler, K.H., Herling, M., Herling, C.D., Jentzsch, M., Franke, G.-N., Boldt, A., Neumuth, T., Shah, U.A., Köhl, U., Reiche, K., Denecke, T., Platzbecker, U., Vučinić, V., Meyer, H.-J. and Merz, M. (2026), Body composition predicts poor outcomes and reveals immunometabolic dysfunction via single-cell profiling in anti-BCMA CAR T-treated myeloma. HemaSphere, 10: e70314. https://doi.org/10.1002/hem3.70314 March 24, 2026.
Overview
CAR-T therapy produces variable outcomes in relapsed and refractory myeloma, and identifying which patients are most likely to benefit — or to do poorly — before treatment begins is an active area of research. This study examined whether body composition measured from routine CT imaging before treatment could predict outcomes in 108 myeloma patients who received BCMA-directed CAR-T therapy.
CT scans were used to quantify four body composition parameters: total adipose tissue, subcutaneous adipose tissue (the fat layer beneath the skin), visceral adipose tissue (fat around the internal organs), and skeletal muscle area as a measure of sarcopenia — the loss of muscle mass associated with poor nutritional status and frailty.
Patients with a BMI below 25 had significantly worse overall survival than those with higher BMI. Among the fat tissue measures, low subcutaneous adipose tissue — rather than visceral fat — drove the association between low total adipose tissue and worse outcomes. Low subcutaneous fat was associated with inferior overall survival, lower response rates, and higher levels of soluble BCMA in the blood, the last of which can reduce CAR-T efficacy by acting as a decoy target. Sarcopenia independently predicted worse overall survival. Progression-free survival was not significantly affected by either parameter.
Low subcutaneous fat and sarcopenia both correlated with lower numbers of bystander T cells at the time of cell collection. Longitudinal immune profiling — including T cell receptor sequencing and single-cell transcriptomics — showed that patients with these body composition features had reduced cytotoxic T cell activity, lower T cell clonal diversity, and higher oxidative phosphorylation activity after infusion, suggesting a less effective immune response following CAR-T treatment.
Both measurements can be extracted from CT scans already performed as part of routine myeloma staging, requiring no additional procedures. The findings suggest that body composition assessment before CAR-T could identify patients who may benefit from nutritional or physical interventions before treatment, though prospective studies would be needed to determine whether improving body composition before infusion translates into better outcomes.
"Diagnosis Disclosure and Related Illness Experience in Patients with Multiple Myeloma and Precursor Plasma Cell Disorders"
Source
Maria A. Malik, Akshay A. Dalvi, Andriy Derkach, Jorge A. Martínez, Jay R. Hydren, Gia Merlo, Ana M. Aldana, Jennifer M. Ahlstrom, Saad Z. Usmani, Susan Chimonas, Robin Ortiz, Urvi A. Shah, Diagnosis Disclosure and Related Illness Experience in Patients with Multiple Myeloma and Precursor Plasma Cell Disorders, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.015. March 24, 2026.
Overview
Telling others about a cancer diagnosis is a personal decision with real consequences for emotional support, relationships, and coping. This survey examined how patients with myeloma and precursor plasma cell disorders — including MGUS and smoldering myeloma — approached diagnosis disclosure and what they experienced as a result.
510 patients responded to a 34-question survey distributed through HealthTree Foundation's patient portal between April and November 2023. 98% had shared their diagnosis with at least one person. Among those who disclosed, 88% did so within a day or a week of diagnosis, 86% shared in person, and the most common recipients were spouses or partners and friends (81% each).
The effects of disclosure were largely positive. 84% of those who shared reported that it helped them cope, and 55% said it strengthened their relationships. 87% did not regret disclosing to anyone. Among the nine patients who had not shared their diagnosis, 56% reported feeling more isolated.
One finding stood out in subgroup analysis: patients with precursor conditions — smoldering myeloma or MGUS — were less likely to report coping well than patients with active myeloma (56% versus 78%, p < 0.001). The authors suggest this may reflect the particular uncertainty of living with a condition that may or may not progress, without the clarity that an active treatment course can sometimes provide.
In open-ended responses, participants advising newly diagnosed patients emphasized considering timing before disclosing, starting with close relationships, maintaining privacy where desired, and learning about the diagnosis before sharing it with others.
The survey reached patients through a single patient advocacy platform, which may not represent the full range of experiences across different demographics or health literacy levels.
"Isolation and profiling of single circulating tumor cells in myeloma: a new workflow for liquid biopsies"
Source
Shifrin, Y., Alikhah, A., Husain, Z., Nguyen, M., Baslik, A., Dyck, D., … Mai, S. (2026). Isolation and profiling of single circulating tumor cells in myeloma: a new workflow for liquid biopsies. BioTechniques, 78(1–12), 123–136. https://doi.org/10.1080/07366205.2026.2645352 March 24, 2026.
Overview
Monitoring how much myeloma remains after treatment — minimal residual disease testing — currently requires bone marrow biopsy, which is invasive, expensive, and cannot be performed frequently. Circulating tumor cells (CTCs) shed by myeloma into the bloodstream offer a potential alternative, but isolating them in sufficient numbers and quality for detailed analysis has been technically difficult. This study described a proof-of-concept workflow for capturing myeloma CTCs from peripheral blood and performing detailed molecular profiling on them.
The isolation method used size-based filtration — passing blood through a membrane that retains larger tumor cells while smaller normal blood cells pass through. In controlled experiments spiking known numbers of myeloma cells into blood samples, the method detected approximately one tumor cell per ten million white blood cells, establishing analytical sensitivity comparable to some bone marrow-based methods.
Critically, the isolated cells retained their structural integrity — nuclear morphology was preserved well enough to allow immunophenotyping (identifying surface proteins to confirm the cells are myeloma plasma cells) and three-dimensional telomere FISH analysis. Telomeres are the protective caps at chromosome ends, and abnormal telomere patterns are associated with genomic instability and disease progression in myeloma. The workflow enabled single-cell telomere profiling, revealing distinct telomeric features in myeloma CTCs compared to normal lymphocytes.
The researchers applied the workflow to blood samples from myeloma patients at different disease stages and demonstrated feasibility across that range.
The method measures genomic instability rather than simply counting tumor cells, which may provide different — and potentially complementary — information to standard MRD tests. Whether telomere-based CTC profiling from blood predicts clinical outcomes as reliably as bone marrow MRD testing would require validation in larger prospective studies.
"FREEDOMM: Fifth-Line or Later Real-World Evaluation of Efficacy and Disease Outcomes in Multiple Myeloma with Ciltacabtagene Autoleucel: Treatment-Free Interval and Overall Survival in the USA"
Source
Ailawadhi, S., Hansen, D.K., Dhakal, B. et al. FREEDOMM: Fifth-Line or Later Real-World Evaluation of Efficacy and Disease Outcomes in Multiple Myeloma with Ciltacabtagene Autoleucel: Treatment-Free Interval and Overall Survival in the USA. Adv Ther (2026). https://doi.org/10.1007/s12325-026-03554-y March 24, 2026.
Overview
Ciltacabtagene autoleucel (cilta-cel) was approved in the US in February 2022 for relapsed or refractory myeloma after four or more prior lines of therapy. This study examined how the drug performs in routine clinical practice using insurance claims data from 242 patients treated between 2016 and June 2024.
Mean age was 63 years; 46% were female. Median follow-up was 11 months. At 18 months after infusion, 80% of patients had not yet started a next line of treatment — the treatment-free interval endpoint used as a proxy for progression-free survival — and 93% were still alive. Median treatment-free interval and median overall survival had not been reached at the time of analysis.
75% of patients received bridging therapy — treatment given between T cell collection and CAR-T infusion to control disease during the manufacturing period. Patients who received bridging therapy had higher comorbidity burden and higher frailty scores than those who did not, indicating they represented a sicker group at baseline. Despite that, bridging therapy recipients were numerically less likely to experience a treatment-free interval event (HR 0.76) and more likely to remain alive (HR 0.48) than those without bridging therapy, though neither difference reached statistical significance given the wide confidence intervals.
The findings are consistent with outcomes from the CARTITUDE-4 pivotal trial and add real-world evidence that cilta-cel produces durable disease control in heavily pretreated patients treated outside of clinical trial conditions. The short median follow-up and claims-based data source — which lacks granular clinical detail on disease characteristics, response depth, and toxicity — limit the conclusions that can be drawn.
"Enhanced dynamic risk stratification of smoldering multiple myeloma"
Source
Chabrun, F., Schwartz, D.E., Gentile, S. et al. Enhanced dynamic risk stratification of smoldering multiple myeloma. Nat Med (2026). https://doi.org/10.1038/s41591-026-04304-x March 24, 2026.
Overview
Ciltacabtagene autoleucel (cilta-cel) was approved in the US in February 2022 for relapsed or refractory myeloma after four or more prior lines of therapy. This study examined how the drug performs in routine clinical practice using insurance claims data from 242 patients treated between 2016 and June 2024.
Mean age was 63 years; 46% were female. Median follow-up was 11 months. At 18 months after infusion, 80% of patients had not yet started a next line of treatment — the treatment-free interval endpoint used as a proxy for progression-free survival — and 93% were still alive. Median treatment-free interval and median overall survival had not been reached at the time of analysis.
75% of patients received bridging therapy — treatment given between T cell collection and CAR-T infusion to control disease during the manufacturing period. Patients who received bridging therapy had higher comorbidity burden and higher frailty scores than those who did not, indicating they represented a sicker group at baseline. Despite that, bridging therapy recipients were numerically less likely to experience a treatment-free interval event (HR 0.76) and more likely to remain alive (HR 0.48) than those without bridging therapy, though neither difference reached statistical significance given the wide confidence intervals.
The findings are consistent with outcomes from the CARTITUDE-4 pivotal trial and add real-world evidence that cilta-cel produces durable disease control in heavily pretreated patients treated outside of clinical trial conditions. The short median follow-up and claims-based data source — which lacks granular clinical detail on disease characteristics, response depth, and toxicity — limit the conclusions that can be drawn.
"Efficacy and safety of selinexor combined with VRD in newly diagnosed multiple myeloma with EMD: a phase 2 trial"
Source
Yuanyuan Jin, Xin Cheng, Xuezhong Zhang, Qinglin Shi, Yu Zhu, Jianyong Li, Lei Fan, Lijuan Chen; Efficacy and safety of selinexor combined with VRD in newly diagnosed multiple myeloma with EMD: a phase 2 trial. Blood Adv 2026; 10 (6): 2016–2022. doi: https://doi.org/10.1182/bloodadvances.2025018945 March 24, 2026.
Overview
Extramedullary myeloma — disease that has spread outside the bone marrow into soft tissues or organs — carries a worse prognosis than myeloma confined to the marrow and responds less well to standard treatments. This single-arm phase 2 trial tested whether adding selinexor, an oral drug that blocks nuclear export, to the standard three-drug backbone of bortezomib, lenalidomide, and dexamethasone (the SVRD combination) could produce deep responses in newly diagnosed patients with extramedullary disease.
30 patients were enrolled between October 2022 and November 2025; 29 received treatment and formed the analysis population. Median age was 60 years. 31% had high-risk cytogenetics and 28% met ultra-high-risk criteria with two or more high-risk features. Induction consisted of four 28-day SVRD cycles, followed by consolidation and maintenance, with autologous stem cell transplant optional for eligible patients.
Among the 29 treated patients, the overall response rate was 90%. 59% achieved a stringent complete response — the deepest measurable level of response. Imaging confirmed extramedullary disease regression in 90% of patients, with complete resolution of extramedullary lesions in 79%.
At a median follow-up of 18 months, 12-month progression-free survival was 88% and 12-month overall survival was 96%; neither median had been reached. 52% of patients proceeded to autologous stem cell transplant.
Grade 3 or higher adverse events occurred in 37% of patients, most commonly thrombocytopenia (24%), pneumonia (10%), and neutropenia (7%). No treatment-related deaths occurred.
The results support SVRD as an active regimen for extramedullary myeloma at diagnosis. The single-arm design and relatively small sample size mean that randomized comparisons against current four-drug standard regimens and cellular therapies will be needed to establish its place in treatment.
"Efficacy and safety profile of busulfan plus low-dose melphalan (BUMEL) versus high-dose melphalan (MEL200) as a conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma patients: a systematic review and meta-analysis"
Source
Maqbool, S., Khan, I., Ibrahim, M., Thida, A. M., Faisal, M. S., Faraz, F., … Rehman, A. (2026). Efficacy and safety profile of busulfan plus low-dose melphalan (BUMEL) versus high-dose melphalan (MEL200) as a conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma patients: a systematic review and meta-analysis. Expert Review of Hematology, 1–11. https://doi.org/10.1080/17474086.2026.2649831 March 24, 2026.
Overview
Before an autologous stem cell transplant, patients receive high-dose chemotherapy to eradicate as much myeloma as possible — a step called conditioning. High-dose melphalan alone has been the standard conditioning regimen for decades, but busulfan combined with melphalan (BUMEL) has been used at some centers as a potentially more potent alternative. This systematic review and meta-analysis pooled data from 11 comparative studies to assess how the two approaches differ in efficacy and toxicity.
BUMEL conditioning was associated with longer progression-free survival than high-dose melphalan alone (hazard ratio 0.83, 95% CI 0.76–0.89), a statistically significant difference. Overall survival did not differ significantly between the two regimens (HR 1.10, 95% CI 1.00–1.21, p = 0.05), meaning the improvement in disease control with BUMEL did not translate into a clear survival advantage.
BUMEL was associated with higher rates of three specific toxicities: mucositis (inflammation of the mouth and gastrointestinal lining), infections, and liver toxicity. These are clinically meaningful differences, as mucositis affects quality of life and the ability to eat during the transplant period, and liver toxicity can occasionally be serious.
The findings present a trade-off: BUMEL offers better disease control but at the cost of greater toxicity, without a demonstrated survival benefit. The authors suggest that conditioning choice should be individualized — weighing a patient's ability to tolerate the additional toxicity of BUMEL against the potential for deeper disease suppression — particularly in settings where upfront transplant remains standard practice and the choice of conditioning has not been superseded by newer induction regimens.
"Meaningful change in patient-reported outcomes after CAR-T for multiple myeloma: differences by race and ethnicity"
Source
Laura B. Oswald, Xiaoyin Li, Carina E. Ferraris, Gabe De Avila, David Scheiber-Camoretti, Lisa M. Gudenkauf, Brent J. Small, Brian D. Gonzalez, Aasha I. Hoogland, Oanh Nguyen, Yvelise Rodriguez, Sylvia L. Crowder, Nathan Parker, Tiffany L. Carson, Christine E. Vinci, Rachid C. Baz, Kenneth H. Shain, Brandon Blue, Ariel F. Grajales-Cruz, Kristy Matte, Brandon Kale, David Kaldas, Fabiana Perna, Melissa Alsina, Ciara L. Freeman, Omar Castaneda Puglianini, Taiga Nishihori, Hien Liu, Frederick L. Locke, Heather S. L. Jim, Doris K. Hansen, Lauren C. Peres; Meaningful change in patient-reported outcomes after CAR-T for multiple myeloma: differences by race and ethnicity. Blood Adv 2026; 10 (6): 1959–1963. doi: https://doi.org/10.1182/bloodadvances.2025018951 March 24, 2026.
Overview
Most studies of CAR-T therapy measure response rates and survival, but how patients feel before and after treatment has received less attention, particularly in real-world settings and across different racial and ethnic groups. This study measured patient-reported outcomes in 99 adults with relapsed or refractory myeloma receiving standard-of-care CAR-T at a single center, comparing results between non-Hispanic White patients and patients from racial and ethnic minority groups.
Participants completed validated questionnaires before lymphodepleting chemotherapy and again 90 days after CAR-T infusion. 32% identified as racial or ethnic minorities (16 non-Hispanic Black, 15 Hispanic, 1 other). Minority participants had lower household incomes and higher employment rates than non-Hispanic White participants. Best overall response rate was 88% across the full cohort.
Average quality-of-life scores were within normal ranges for both groups at both time points, with moderate pain intensity and mildly impaired physical function as exceptions. The two groups did not differ in average scores or in the proportion reporting meaningful deficits at either time point.
Looking at change from baseline to day 90, nearly half of all participants had meaningfully improved overall quality of life, physical wellbeing, emotional wellbeing, and pain interference — findings consistent with the known disease control benefits of CAR-T.
Three differences emerged between racial and ethnic groups. Minority participants were more likely to have meaningfully improved fatigue (47% versus 26%) but also more likely to have meaningfully worsened fatigue (27% versus 16%) — a divergence suggesting greater variability in how CAR-T affects this symptom in minority patients. Minority participants were more likely to have meaningfully improved pain intensity (50% versus 19%). They were also more likely to report meaningfully worsened social function (40% versus 20%).
These differences held after adjusting for age, performance status, disease risk features, and prior BCMA therapy. The sample size limited more detailed comparisons between individual minority subgroups, and 90 days is a single snapshot that does not capture longer-term trajectories.
"Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models"
Source
Mackenzie M. Lieberman, Jason H. Tong, Nkechi U. Odukwe, Colin A. Chavel, Gina G. Bishara, Kimberly M. Crasti, Megan M. Herr, Payal Goala, Terence J. Purdon, Rebecca Burchett, Bryan M. Gillard, Craig M. Brackett, Joseph D. Tario, Spencer R. Rosario, A.J. Robert McGray, Jonathan L. Bramson, Marco L. Davila, Renier J. Brentjens, Ehsan Malek, Kelvin P. Lee, Scott H. Olejniczak; Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-25-0092 March 25, 2026.
Overview
Most patients treated with BCMA-directed CAR-T therapy for myeloma eventually relapse. One hypothesis for why is that CAR-T cells lose effectiveness over time due to exhaustion or insufficient survival signaling. CD28 is a co-stimulatory receptor on T cells that promotes their survival and proliferation, and the researchers hypothesized that blocking CD28 signaling on myeloma cells — which express CD28's binding partners CD80 and CD86 — might reduce a survival advantage the cancer cells exploit. Instead, they found the opposite.
When CD28 interaction with CD80/CD86 was blocked in preclinical myeloma and lymphoma CAR-T models, tumors regrew faster, not slower. Follow-up experiments using genetic knockout of CD28 on the CAR-T cells themselves revealed why: endogenous CD28 signaling on the infused T cells — not on the tumor cells — was doing the important work. CAR-T cells with intact CD28 signaling persisted longer in vivo, maintained better mitochondrial energy balance and redox homeostasis, and produced inflammatory cytokines in the tumor environment that were associated with tumor control. Removing CD28 from the CAR-T cells compromised all of these functions.
When CD28 blockade was applied transiently rather than continuously, it reduced levels of some cytokines in the tumor environment without significantly affecting survival of treated mice — a partial dissociation between cytokine effects and overall outcome.
The findings demonstrate that endogenous CD28 signaling on 4-1BB co-stimulated CAR-T cells contributes to their effectiveness in myeloma and lymphoma models, and that blocking this signal — even with the intention of targeting tumor cell survival — may undermine the CAR-T cells themselves. The work was conducted in preclinical models; how these findings translate to human CAR-T therapy requires further investigation.
"Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma"
Source
Schjesvold F, Spencer A, Cohen YC, et al. Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma. Cancer. 2026;e70341. doi:10.1002/cncr.70341 March 25, 2026.
Overview
BCMA is the most commonly targeted protein in myeloma immunotherapy, but one challenge with BCMA-directed treatments is that BCMA can be shed from the myeloma cell surface by an enzyme called gamma-secretase, reducing the amount available for targeting. Gamma-secretase inhibitors block that shedding and increase surface BCMA levels, potentially improving the effectiveness of BCMA-directed drugs. This phase 1 study tested a new BCMA×CD3 bispecific antibody called WVT078 both alone and combined with the gamma-secretase inhibitor WHG626 in 56 patients with relapsed or refractory myeloma.
The primary goals were to establish safety, tolerability, and recommended doses for further study. Cytokine release syndrome was the most common treatment-related side effect across all dose levels. Seven patients experienced dose-limiting toxicities.
WVT078 alone produced an overall response rate of 27% and a complete response rate of 12%. When combined with WHG626, the overall response rate was 48% and the complete response rate was 22% — numerically higher across both measures, though the study was not designed to formally compare the two approaches.
Recommended doses for expansion were not declared and dose expansion was not initiated, meaning the trial did not progress to its next planned stage. The reasons for this are not detailed in the abstract.
The combination of a BCMA bispecific antibody with a gamma-secretase inhibitor produced more responses than the antibody alone in this early-stage study. Whether that improvement is clinically meaningful and durable would require larger studies with longer follow-up.
"Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma"
Source
Kumar, S., Jagannath, S., Weisel, K.C. et al. Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01466-2 March 25, 2026.
Overview
Linvoseltamab is a bispecific antibody that targets BCMA on myeloma cells and CD3 on T cells. The LINKER-MM1 phase 1/2 trial tested it in patients with relapsed or refractory myeloma who had received three or more prior lines of therapy and were exposed or refractory to three drug classes. Because the trial lacked a randomized control arm, the researchers constructed an external control arm from real-world patient data to provide context for the efficacy results.
The comparison included 105 patients who received linvoseltamab at the 200 mg dose in LINKER-MM1 and 203 patients from International Myeloma Working Group centers whose medical records confirmed they met the same eligibility criteria and received standard care. An independent committee reviewed the real-world data for quality and comparability, and inverse probability of treatment weighting was applied to balance baseline characteristics between the two groups before comparison.
Linvoseltamab produced a higher response rate than standard care (weighted odds ratio 3.0). Progression-free survival was longer with linvoseltamab (weighted hazard ratio 0.33), as was time to next treatment (wHR 0.34) and overall survival (wHR 0.72). All comparisons favored linvoseltamab.
The external control design is an important limitation to note. Patients in observational datasets differ from trial participants in ways that statistical weighting cannot fully correct — selection into a clinical trial, the intensity of monitoring, and supportive care practices all differ from routine practice. The comparison nonetheless provides a reference point for interpreting linvoseltamab's activity in a population where randomized data against standard care are not available.
"In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study"
Source
An, N., Wang, D., Zhang, P. et al. In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study. Nat Med (2026). https://doi.org/10.1038/s41591-026-04244-6 March 25, 2026.
Overview
Standard CAR-T therapy requires collecting a patient's T cells, sending them to a manufacturing facility where they are genetically modified over several weeks, and then reinfusing them — a process that delays treatment, requires lymphodepleting chemotherapy to prepare the body, and limits access to centers with specialized infrastructure. This phase 1 trial tested a different approach: delivering the CAR gene directly into the patient's T cells using a viral vector administered as a single intravenous infusion, bypassing cell collection, manufacturing, and lymphodepletion entirely.
The drug, ESO-T01, is a lentiviral vector engineered to target T cells in the body and deliver a BCMA-directed CAR gene. Five heavily pretreated male patients with relapsed or refractory myeloma received a single infusion at a dose of 0.2 × 10⁹ transduction units. Median prior lines of therapy were three. Median follow-up was six months. The trial was stopped early in 2025 and no additional patients were enrolled.
No dose-limiting toxicities occurred. All five patients experienced at least one grade 3 or higher adverse event. Cytokine release syndrome occurred in four patients — three at grade 3 and one at grade 2 — and was managed with corticosteroids, tocilizumab, or supportive care. The most common toxicities were transient low blood counts and reversible liver enzyme elevations; three patients had grade 2 infections. One patient developed grade 1 neurological toxicity and died from spinal cord compression caused by extramedullary myeloma lesions.
Four of five patients achieved an objective response, including three stringent complete remissions. All four evaluable responders had no detectable residual disease at the level of one cell in 100,000 by day 60.
The results provide early evidence that in vivo CAR-T generation is feasible and can produce deep responses in heavily pretreated myeloma without leukapheresis or lymphodepletion. The small number of patients, early trial termination, and short follow-up mean these findings should be interpreted as preliminary.
"Impact of clinical surveillance on myeloma-related complications in patients with precursor plasma cell disorders"
Source
Koo, E., Albert, S., Patrick, B. et al. Impact of clinical surveillance on myeloma-related complications in patients with precursor plasma cell disorders. Blood Cancer J. 16, 40 (2026). https://doi.org/10.1038/s41408-026-01463-5 March 26, 2026.
Overview
Multiple myeloma is almost always preceded by a precursor condition — either monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma — that can be detected years before active disease develops. This retrospective study examined whether patients who were already being followed for a precursor condition fared better at the time of myeloma diagnosis than those in whom myeloma was the first plasma cell diagnosis.
415 patients diagnosed with myeloma at a single Canadian tertiary center between January 2019 and July 2024 were included. 95 had a prior documented precursor diagnosis (71 MGUS, 16 smoldering myeloma, 8 solitary plasmacytoma) at least three months before myeloma was diagnosed. The remaining 320 had no known precursor history.
Patients with a prior precursor diagnosis presented with substantially less organ damage. Rates of anemia (35% versus 65%), kidney impairment (11% versus 23%), bone lesions (45% versus 59%), and high calcium (6% versus 13%) were all lower.
Pathological fractures (26% versus 42%), spinal cord compression (6% versus 13%), dialysis (2% versus 8%), and blood transfusions (16% versus 39%) were also less common. Emergency department presentations before diagnosis occurred in 37% of the monitored group versus 64% of those without prior follow-up, and hospitalizations in 35% versus 57%.
Time from symptom onset to diagnosis was shorter in the monitored group — 4.5 months versus 7.6 months — suggesting that patients already engaged in hematology care sought assessment more quickly when new symptoms appeared.
In multivariate analysis accounting for age and sex, a prior precursor diagnosis was associated with a 71% reduction in the odds of experiencing a composite of serious myeloma-defining complications at diagnosis — including fracture, spinal cord compression, dialysis, hospitalization, high calcium requiring treatment, and blood transfusion.
No significant difference in progression-free or overall survival was observed, though the authors note the cohort may be too small and follow-up too short to detect a survival benefit that larger population studies have estimated at 13–14%.
The findings suggest that the benefit of monitoring precursor conditions extends beyond survival to include less severe disease at presentation and lower healthcare utilization — outcomes that population-level survival data do not capture.
"Evolution of multiple myeloma from a genomic perspective"
Source
Francesco Maura, Mehmet Samur, Nikhil Munshi; Evolution of multiple myeloma from a genomic perspective. Blood 2026; 147 (13): 1423–1432. doi: https://doi.org/10.1182/blood.2024026313 March 26, 2026.
Overview
Multiple myeloma is almost always preceded by precursor conditions — MGUS and smoldering myeloma — that can be present for years or decades before active disease appears. This review examined the biological processes that drive progression from those precursor states to myeloma requiring treatment.
Genetic predisposition shapes the starting point. Both inherited germline variants and myeloma-specific genetic loci influence who develops the disease. Racial disparities in the rates of MGUS and myeloma — with higher incidence in Black populations than in White populations — suggest that predisposition varies across groups and that the existing evidence base, drawn largely from studies in White patients, may not fully represent the biology across all affected populations.
The earliest genomic events in myeloma development include chromosomal translocations and hyperdiploidy — gains of extra chromosomes — which occur in the precursor stage and are thought to be necessary but not sufficient for progression to active disease. Further steps are required to convert a stable precursor into symptomatic myeloma. One well-characterized mechanism is positive selection of subclonal populations — genetic variants that give certain plasma cell clones a growth advantage, allowing them to expand over time at the expense of other clones.
That selection process is influenced by aging and by environmental exposures. Agent Orange and agricultural chemicals have been associated with increased myeloma risk, and aging broadly alters both the immune environment and the DNA repair capacity of cells in ways that may favor clonal expansion.
Immune surveillance — the immune system's ability to recognize and eliminate abnormal cells — plays a role throughout this process. As precursor clones evolve and accumulate genetic changes, they may acquire the ability to evade immune detection, a step that likely contributes to the transition from smoldering to active disease.
The review argues that integrating genomic, transcriptomic, and immune profiling data with clinical characteristics offers the best current approach to identifying which precursor patients are at high enough risk to warrant closer monitoring or early intervention.
"Time to revise myeloma diagnostic criteria? A decade of accumulated evidence on a serum free light chain ratio of ≥100"
Source
Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin; Time to revise myeloma diagnostic criteria? A decade of accumulated evidence on a serum free light chain ratio of ≥100. Blood 2026; 147 (13): 1412–1415. doi: https://doi.org/10.1182/blood.2025031907 March 26, 2026
Overview
When the International Myeloma Working Group updated myeloma diagnostic criteria in 2014, it added a serum free light chain (sFLC) ratio of 100 or above as a standalone criterion for diagnosing active myeloma requiring treatment. The rationale was that studies at the time suggested roughly 80% of patients with this finding would progress to symptomatic myeloma within two years. Subsequent data have told a different story.
Population-based registry data now show a two-year progression risk of around 30% in patients identified solely by an sFLC ratio at or above 100 — less than half the originally estimated rate. Among patients with an sFLC ratio at or above 100 who also have less than 200 mg of monoclonal protein in a 24-hour urine collection — more than 70% of that group — the two-year progression risk drops to 13.5%, and the risk of irreversible kidney failure is minimal.
The authors identify a practical consequence of the current criteria beyond overdiagnosis. Because an sFLC ratio at or above 100 is embedded in the composite progression-free survival endpoint used in clinical trials of high-risk smoldering myeloma, patients who experience a rise in this ratio during a trial may be counted as having progressed — even if they have no symptoms or organ damage. That classification inflates apparent progression events and may misrepresent the benefit or harm of early interventions.
The authors propose two changes: removing the sFLC ratio criterion as a standalone myeloma-defining event, and excluding patients diagnosed solely on this basis from trials of newly diagnosed myeloma. Instead, they argue these patients should be enrolled in prospective smoldering myeloma studies with active surveillance using modern imaging, to better characterize their natural history under current diagnostic and treatment conditions.
"Deciphering the Genetic Underlying Causes of Sex Differences in Multiple Myeloma Incidence and Mortality"
Source
Ajibola Opakunle, Yuting Shan, Yingbo Huang, Christina Printzis, Catherine Therese Stanhope, Barbara E. Stranger, Rong Stephanie Huang, Deciphering the Genetic Underlying Causes of Sex Differences in Multiple Myeloma Incidence and Mortality, Human Genetics and Genomics Advances, 2026, 100596, ISSN 2666-2477, https://doi.org/10.1016/j.xhgg.2026.100596. March 26, 2026.
Overview
Myeloma occurs more frequently in men than women and is associated with worse outcomes in men, but the biological reasons for that disparity have not been well characterized. This study tested the hypothesis that sex-specific differences in how somatic mutations regulate gene expression in myeloma cells drive different patterns of genetic dependency between male and female tumors.
The researchers first identified genes expressed at different levels in male versus female myeloma cells. They then looked for somatic mutations — mutations acquired by the tumor rather than inherited — that regulate those sex-biased genes differently depending on sex. Genes identified through this analysis were evaluated for their association with overall survival outcomes in myeloma patients, stratified by sex. Finally, the functional importance of candidate genes was tested using CRISPR-Cas9 dependency screens in myeloma cell lines, which identify genes that cancer cells cannot survive without.
The analysis produced systematic evidence that myeloma tumors in men and women are regulated differently at a molecular level — not only in which genes are expressed, but in which genes the cancer cells depend on for survival. Those dependencies represent potential therapeutic targets, and the sex-specificity of some dependencies suggests that treatments targeting them may produce different effects in male and female patients.
The findings argue for incorporating sex as a variable in myeloma molecular research rather than treating it as a demographic characteristic of limited biological relevance. Whether sex-specific genetic dependencies translate into differences in treatment response or outcomes in clinical practice would require prospective validation.
"Abstract A018: Functional chemo-genomic screening identifies novel combination therapies to treat RAS-driven multiple myeloma"
Source
Omar S. Al-Odat, Arnold Bolomsky, Michele Ceribelli, Lin Zhang, Constantine S. Mitsiades, Craig J. Thomas, Ryan M. Young; Abstract A018: Functional chemo-genomic screening identifies novel combination therapies to treat RAS-driven multiple myeloma. Cancer Res 1 March 2026; 86 (5_Supplement_1): A018. https://doi.org/10.1158/1538-7445.RASONCOTHER26-A018
Overview
Mutations in RAS family genes (KRAS and NRAS) or in FGFR3 occur in more than half of myeloma cases and drive tumor growth, but drugs that directly target RAS have been difficult to develop and none are currently approved for myeloma. This study used large-scale drug screening and genomic tools to identify how a new pan-RAS inhibitor called RMC-6236 works in myeloma and which drugs enhance its effects.
RMC-6236 works by forming a three-way complex with RAS and a chaperone protein, blocking RAS from activating downstream signaling. The researchers tested it against nearly 3,000 clinical-stage compounds from the MIPE 6.0 library across multiple myeloma cell lines to identify synergistic combinations systematically.
RMC-6236 showed activity in the low nanomolar range — meaning very small concentrations were sufficient — across more than 50 genetically diverse myeloma cell lines. Cell lines with RAS or FGFR3 mutations were more sensitive than others.
Phosphoproteomic analysis confirmed the drug suppressed two key cancer growth pathways — MAPK and mTORC1 — and proximity ligation assays confirmed it physically disrupted RAS interactions with its downstream effectors MEK, mTOR, and SLC3A2.
The top synergistic partner identified in the screen was FHD-286, an inhibitor of SWI/SNF chromatin remodeling complexes. Combining RMC-6236 with FHD-286 enhanced cell death and arrested cells in the G1 phase of the cell cycle more effectively than either drug alone. The mechanistic logic is that RAS inhibition blocks proliferative signaling while SWI/SNF inhibition disrupts the chromatin remodeling that cancer cells use to maintain their gene expression programs.
In mouse models carrying KRAS- and NRAS-driven myeloma tumors, RMC-6236 produced rapid tumor regression under a clinically feasible induction-maintenance dosing schedule, with no treatment-related deaths or significant toxicity observed.
The findings support advancing RMC-6236, alone and in combination with FHD-286, into clinical trials in myeloma patients whose tumors carry RAS or FGFR3 alterations. Human studies have not yet been conducted.
"Dosing patterns for talquetamab, including dose de-escalation, in a real-world setting"
Source
Rahul Banerjee, Ruibin Wang, Hsien-Yen Chang, Jinghua He, Ibrahim Saber, Kathleen Gray, Xinke Zhang, Yi-Hsuan Liu, Dosing patterns for talquetamab, including dose de-escalation, in a real-world setting, Blood Immunology & Cellular Therapy, 2026, 100045, ISSN 3050-5976, https://doi.org/10.1016/j.bict.2026.100045. March 26, 2026.
Overview
Talquetamab is a bispecific antibody targeting GPRC5D and CD3, approved for relapsed or refractory myeloma. It is initiated with a step-up dosing schedule to reduce cytokine release syndrome risk, followed by either weekly or every-two-week maintenance dosing. This retrospective analysis examined how talquetamab has been used in routine US practice using two large national databases — one hospital-based (273 patients, treated through March 2025) and one outpatient-based (257 patients, treated through January 2025).
Both databases included older and minority patients often underrepresented in clinical trials: 15% and 21% of patients respectively were aged 75 or older, and 26% and 15% were Black. 12% of patients in the hospital database were treated at non-academic centers. Median prior lines of therapy were five, and 58% had previously received a BCMA-directed therapy.
Step-up dosing was conducted in an inpatient setting in 80% of cases. Cytokine release syndrome occurred in 42% of patients and ICANS in 14% — rates consistent with trial data. Most patients received talquetamab as monotherapy, but combination use was observed in 10% of cases. A notable pattern was planned talquetamab use as bridging therapy before BCMA CAR-T infusion, occurring in 14% of patients.
Among the 95 patients with at least six months of follow-up, dosing had shifted toward less frequent schedules: 56% were on every-two-week dosing and 33% on every-four-week or longer intervals — suggesting that de-escalation is occurring in routine practice as it did in clinical trials.
The databases lacked detailed toxicity grading, limiting the ability to characterize safety in depth. The findings document how the drug's use is evolving within two years of approval, with less frequent dosing, combination approaches, and pre-CAR-T bridging emerging as real-world patterns beyond the initially approved monotherapy indication.
"Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Receiving Teclistamab: A Panel Chart Review Study"
Source
Dhakal, B., Levy, M.Y., Ko, G. et al. Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Receiving Teclistamab: A Panel Chart Review Study. Oncol Ther (2026). https://doi.org/10.1007/s40487-026-00429-8 March 26, 2026.
Overview
Teclistamab is a BCMA×CD3 bispecific antibody approved for relapsed or refractory myeloma based on the MajesTEC-1 trial. Existing real-world data have come largely from academic centers with short follow-up. This retrospective study examined 101 patients treated with teclistamab at community oncology practices within Cardinal Health's provider network, offering a view of how the drug performs outside academic settings.
Median age was 65 years. 86% had an ECOG performance status of 1, and 38% had high-risk cytogenetics. 93% were triple-class exposed and 65% were triple-class refractory. Median follow-up was 13.8 months.
Overall response rate was 80% across the full cohort. Among the 30 patients whose treatment aligned with US prescribing information criteria, the response rate was 90%. Among the 71 patients treated outside those criteria — reflecting real-world use beyond the approved label — it was 76%.
Cytokine release syndrome occurred in 33% of patients during step-up dosing and ICANS in 9%. 27% of patients developed infections while on treatment.
The overall response rate of 80% is numerically higher than the 63% reported in MajesTEC-1, despite this cohort having higher disease burden and worse performance status on average than trial participants. The authors note this may reflect differences in how response was assessed, patient selection within a community setting, or the longer median follow-up allowing more responses to be captured. Adverse event rates were broadly similar to trial data.
The findings suggest teclistamab produces meaningful responses in community practice, including in patients who would not have met clinical trial eligibility criteria.
"Burden of Disease, Treatment Patterns, and Clinical Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Receiving Teclistamab: A Panel Chart Review Study"
Source
Cardé, N.A.Q., Niu, J., Guo, Y. et al. Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01205-4 March 26, 2026.
Overview
Myeloma incidence, treatment patterns, and outcomes vary substantially across regions, shaped by differences in ethnicity, healthcare access, and socioeconomic factors. This systematic review examined the available evidence on myeloma epidemiology and management in four Middle East and North Africa (MENA) countries — Egypt, Saudi Arabia, Turkey, and the United Arab Emirates — drawing on 94 studies identified from a PubMed and Embase search covering January 2015 to May 2025.
Most included studies were retrospective and observational; more than half were conducted in Turkey. The age-standardized incidence rate in the MENA region was 1.49 per 100,000 people in 2019, lower than rates reported in Western countries. Median age at diagnosis ranged from 43 to 70 years across studies — younger than the global median of approximately 70 years, a pattern that may reflect differences in population age structure, diagnostic access, or disease biology.
Bortezomib-containing regimens were used in 50% of patients, making bortezomib the most commonly used drug. Lenalidomide was the second most frequently used agent in newly diagnosed disease, and daratumumab in relapsed or refractory disease. Fewer than 1% of patients received quadruplet regimens, which are increasingly standard in high-income countries.
Overall response rates ranged from 35% to 90%, reflecting heterogeneity across study populations and treatment eras. Progression-free survival ranged from 2 to 97.7 months and overall survival from 4 to 125.3 months — wide ranges that limit meaningful comparison across studies. Hematologic toxicities and peripheral neuropathy were the most commonly reported adverse events, though reporting was inconsistent across studies.
Data on healthcare resource utilization were sparse across all four countries. The review identifies a significant gap in comprehensive, prospective epidemiological data for the region, and notes that limited access to newer treatment combinations — including four-drug induction regimens and immunotherapies — may be contributing to outcome differences relative to other regions.
"Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics"
Source
Cardé, N.A.Q., Niu, J., Guo, Y. et al. Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01205-4 March 26, 2026.
Overview
Teclistamab is given using a step-up dosing schedule at initiation — two lower priming doses before the first full dose — to reduce the risk of cytokine release syndrome. When patients need to pause treatment due to side effects, surgery, or other reasons, a practical question arises: how long a gap requires repeating those priming doses before resuming full-dose treatment? This study used pharmacokinetic modeling, cytokine dynamics simulation, and retrospective clinical data to answer that question.
Pharmacokinetic modeling estimated how quickly teclistamab blood levels fall during a treatment gap and at what point they drop to levels comparable to those seen after each step-up dose. Median drug levels were estimated to fall to second step-up dose trough levels after 62 days and to first step-up dose trough levels after 111 days. Cytokine dynamics modeling suggested that restarting treatment at these intervals would produce lower cytokine peaks than the original step-up dosing — meaning the immune activation on restart would be less intense than at treatment initiation.
These modeling-derived thresholds were then applied to clinical data from the MajesTEC-1 trial. Among 61 patients who resumed teclistamab following a dose delay using the approach recommended in the study, CRS occurred in only two patients (3.3%), both grade 1 or 2.
Based on these analyses, the authors propose the following approach: gaps of 62 days or less can be managed by resuming full-dose treatment without any step-up doses; gaps of 63 to 111 days require repeating the second step-up dose before resuming; gaps longer than 111 days require repeating both step-up doses from the beginning as per the original label. These recommendations offer a practical framework for managing treatment interruptions while minimizing unnecessary step-up procedures for patients with shorter gaps.
"Oncolytic bovine herpesvirus type 1 induces immune microenvironment remodeling and enhances treatment responses in multiple myeloma"
Source
Raimondi V, Vescovini R, Storti P, Franceschi V, Pozzi G, Sitzia C, Iannozzi NT, Toscani D, Dalla Palma B, Scita M, Dessena M, Minesso S, Ricci S, Mohammadi F, Lungu O, Mirandola P, Donofrio G, Giuliani N. Oncolytic bovine herpesvirus type 1 induces immune microenvironment remodeling and enhances treatment responses in multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2025.289317 [Early view]. March 26, 2026.
Overview
Oncolytic virotherapy uses viruses that selectively infect and destroy cancer cells while leaving normal cells intact. A persistent challenge with human viruses is that most people have pre-existing immunity that neutralizes them before they can reach the tumor. This study tested bovine herpesvirus type 1 (BoHV-1) — a virus that infects cattle but does not cause disease in humans — as a potential treatment for myeloma, reasoning that human immune systems would not have prior immunity to it.
BoHV-1 infected myeloma cells efficiently and killed them through mitochondrial apoptosis. In infected myeloma cells, the virus suppressed several survival programs — including MYC-driven gene expression, oxidative phosphorylation, and the unfolded protein response — that myeloma cells depend on. It also altered the surface of infected cells in ways that made them more visible to NK cells: NK-activating ligands were upregulated and MHC class I molecules, which normally shield cells from immune attack, were downregulated.
When tested in bone marrow samples taken directly from myeloma patients, BoHV-1 selectively reduced malignant plasma cells and immunosuppressive myeloid cells while sparing normal lymphoid cells and blood-forming progenitor cells. The virus activated CD8+ T cells, NK cells, and monocytes, and shifted macrophage-like cells toward a pro-inflammatory state. Depleting monocytes from the samples reduced the anti-myeloma effect, identifying them as functionally important mediators of the response. The infection produced a broad inflammatory cytokine response dominated by type I and type II interferons.
Combining BoHV-1 with bortezomib or lenalidomide increased myeloma cell killing beyond either agent alone. The virus also upregulated CD38 on both myeloma cells and immune effectors, which increased sensitivity to daratumumab — suggesting BoHV-1 could prime tumors for CD38-directed antibody therapy.
All experiments were conducted in cell and patient-derived bone marrow samples. Animal studies and clinical testing have not yet been reported.
"The Association Between Multiple Myeloma and Neuropsychiatric Manifestations: A Narrative Review,” Psycho-Oncology"
Source
Archambault, Joanna Kowalik, and Srinagesh M.Thippaiah. 2026. “The Association Between Multiple Myeloma and Neuropsychiatric Manifestations: A Narrative Review,” Psycho-Oncology: e70438. https://doi.org/10.1002/pon.70438. March 26, 2026
Overview
Up to 43% of people with myeloma develop a psychiatric condition during their illness — a rate substantially higher than in the general population. Depression, anxiety, and cognitive difficulties affect treatment adherence, quality of life, and survival, yet mental health remains less systematically addressed in myeloma care than disease response or physical toxicity. This narrative review examined the mechanisms that may explain the connection between myeloma and neuropsychiatric symptoms.
The review identified four main contributing pathways. First, treatment itself causes psychiatric symptoms. Corticosteroids — used in virtually every myeloma regimen — produce mood instability, insomnia, and in some patients frank psychiatric episodes. Newer BCMA-directed therapies, including bispecific antibodies and CAR-T, can cause neurological toxicity ranging from confusion to more severe encephalopathy.
Second, myeloma drives systemic inflammation through pro-inflammatory cytokines including IL-6 and TNF-alpha, which are known to affect mood, cognition, and the stress response through their effects on the brain. This inflammatory pathway likely contributes to depression and fatigue independent of treatment.
Third, myeloma can directly involve the central nervous system, though this is uncommon. When it occurs, neurological and psychiatric symptoms can result directly from tumor infiltration or compression.
Fourth, myeloma complications produce neuropsychiatric effects through indirect mechanisms. Hypercalcemia causes confusion and mood changes. Anemia contributes to fatigue and cognitive slowing. Infections and chronic pain both independently worsen mental health.
Psychiatric illness in myeloma patients has been associated with higher mortality, reduced quality of life, and higher healthcare costs. The review argues that routine neuropsychiatric screening should be incorporated into myeloma care, and that the mechanisms outlined — particularly inflammation, monoclonal protein effects on the nervous system, and cumulative steroid exposure — warrant further prospective investigation.
"MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM"
Source
Gozzetti A, Pacelli P, Caroni F, Raspadori D, Bestoso E, Antonioli E, et al. MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM. Br J Haematol. 2026;00:1–10. https://doi.org/10.1111/bjh.70448 March 26, 2026.
Overview
Even when myeloma responds well to initial treatment — reaching very good partial response or better — many patients still have small numbers of myeloma cells detectable by sensitive bone marrow testing. This residual disease, measured by next-generation flow cytometry at a sensitivity of one myeloma cell in a million, predicts future relapse. This phase 2 trial tested whether adding daratumumab in patients who were in deep remission but still MRD-positive after first-line therapy could eliminate that residual disease.
Of 110 newly diagnosed myeloma patients screened for MRD positivity at the one-in-a-million threshold, 50 were positive and received six months of daratumumab. Patients who converted to MRD-negative at six months stopped treatment; those who remained positive continued for up to 24 months total.
At the six-month primary endpoint, 15 of 50 patients (30%) had converted to MRD-negative and stopped treatment. At 24 months, 11 of 50 (22%) remained MRD-negative. At a median follow-up of 50 months, 29 patients (58%) had relapsed. Median progression-free survival was 45 months and median overall survival had not been reached.
Achieving MRD negativity at any point during the study carried significant prognostic weight: patients who became MRD-negative at least once had a median progression-free survival of 61 months, compared to 26 months in those who never converted (p = 0.0009). At the time of analysis, 21 of the 50 patients had not progressed, with a median time on follow-up of 44 months in that group.
The findings suggest daratumumab can convert a meaningful proportion of MRD-positive patients to MRD-negative status after first-line therapy, and that achieving that conversion — even transiently — is associated with substantially longer remission. Whether this approach should be adopted more broadly, and how it compares to simply continuing or intensifying standard therapy, would require randomized comparison.
"Non-ICANS Neurologic Toxicity after BCMA CAR T: A systematic review and meta-analysis of 4630 multiple myeloma patients"
Source
Herman J van Besien, Gwynne Ozkan, Neela Easton, Tobias Tix, Mohammad Alhomoud, Roni Shouval, Kai Rejeski, Samuel Yamshon; Non-ICANS Neurologic Toxicity after BCMA CAR T: A systematic review and meta-analysis of 4630 multiple myeloma patients. Blood Adv 2026; bloodadvances.2026019617. doi: https://doi.org/10.1182/bloodadvances.2026019617 March 26, 2026.
Overview
CAR-T therapy for myeloma is well known to cause cytokine release syndrome and a neurological complication called ICANS. Less attention has been paid to other neurological toxicities that do not fit the ICANS definition — a heterogeneous group the authors term non-ICANS neurologic toxicities (NINTs). This systematic review and meta-analysis pooled data from 55 cohorts comprising 4,630 patients treated with BCMA-directed CAR-T to estimate how often NINTs occur and which factors predict higher risk.
The overall pooled incidence of NINTs was 0.81% (95% CI 0.37–1.77%), confirming they are uncommon across the full population of BCMA CAR-T recipients.
Incidence differed substantially by product. Cilta-cel was associated with a NINT rate of 4.6%, compared to 0.5% for ide-cel and 0.3% for experimental BCMA-directed constructs — differences that were statistically significant. Meta-regression confirmed cilta-cel as independently associated with higher NINT risk compared to ide-cel after accounting for other variables.
Among the 133 individual NINT events with sufficient clinical detail for classification, cranial nerve palsies were the most common phenotype (32%), followed by movement and neurocognitive abnormalities (12%) and peripheral neuropathies (8%).
The wide confidence interval around the pooled estimate reflects substantial heterogeneity across studies, driven in part by inconsistent definitions and reporting of neurological toxicities. The authors identify the absence of standardized criteria for NINTs as the primary barrier to accurate characterization — without consistent definitions, events may be missed, miscategorized, or reported differently across trials and real-world datasets.
The findings establish that NINTs, while rare overall, occur at clinically meaningful rates with cilta-cel specifically and represent a toxicity category that warrants more systematic surveillance and reporting.
"Dietary patterns among individuals with plasma cell disorders– opportunities for targeted interventions"
Source
Traore, K., Castro, F., Derkach, A. et al. Dietary patterns among individuals with plasma cell disorders– opportunities for targeted interventions. Blood Cancer J. 16, 42 (2026). https://doi.org/10.1038/s41408-026-01468-0 March 27, 2026.
Overview
Diet quality is associated with cancer risk and survival, and patients with plasma cell disorders — including MGUS, smoldering myeloma, and active myeloma — have reason to be interested in whether dietary changes might affect their disease. This cross-sectional study examined dietary patterns in 500+ individuals with plasma cell disorders who completed a validated food frequency questionnaire through the HealthTree Foundation patient portal between May 2023 and January 2024.
Diet quality was measured using the Healthy Eating Index (HEI-2020), a 100-point score reflecting adherence to the 2020–2025 US Dietary Guidelines. Overall, participants in this study scored higher than the general US population on HEI measures — a finding the authors attribute largely to selection bias, as recruitment occurred through nutrition-focused support group events that likely attracted people already interested in diet.
Several subgroup differences were more clinically informative. Participants with obesity had lower HEI scores and lower fiber intake than those with normal BMI, with trends toward lower vegetable consumption and higher added sugar intake. Given that higher BMI is associated with myeloma progression and mortality, this group may have the most to gain from dietary intervention. Lower education level also correlated with lower fiber intake and a trend toward lower diet quality overall.
Men reported higher caloric intake and lower fiber and vegetable consumption than women. Participants with active myeloma had higher fruit intake than those with precursor conditions, which the authors suggest may partly reflect glucocorticoid use — a standard component of myeloma treatment — altering food preferences toward sweeter, more palatable foods.
Fiber intake was the most consistent differentiator across subgroups, varying by sex, BMI, and education level more reliably than other dietary components.
A practical finding from the authors' prior work contextualizes these results: 57% of patients with plasma cell disorders reported that diet and nutrition were not discussed during their hematology or oncology visits. Whether dietary counseling integrated into routine myeloma care would improve disease-relevant outcomes — including progression rates and survival — is being evaluated in the NUTRIVENTION trials.
"Uptake of Technetium-99m Sestamibi (99mTc-MIBI) as a Predictor of Fracture Risk in the Appendicular Skeleton of Multiple Myeloma Patients at a National Reference Center"
Source
Bañuelos Balderas R, Linares González L, Arguelles Pérez D, et al. (March 27, 2026) Uptake of Technetium-99m Sestamibi (99mTc-MIBI) as a Predictor of Fracture Risk in the Appendicular Skeleton of Multiple Myeloma Patients at a National Reference Center. Cureus 18(3): e105969. doi:10.7759/cureus.105969 March 27, 2026.
Overview
Bone lesions are common in myeloma and frequently lead to pathological fractures — fractures caused by tumor involvement rather than trauma. Whole-body MRI and PET/CT are the most sensitive imaging tools for assessing those lesions, but both remain unavailable in many healthcare settings. This retrospective study examined whether technetium-99m sestamibi (99mTc-MIBI) scintigraphy — a nuclear medicine scan more widely available than MRI or PET/CT — could identify myeloma patients at higher risk of fracture.
121 patients with histologically confirmed myeloma who underwent 99mTc-MIBI scintigraphy between 2014 and 2021 were included. Median age was 61.5 years; 57% were male. Radiotracer uptake was most frequent in the humerus (28%), axial skeleton (17%), and femur (9%).
Pathological fractures occurred in 94 patients (78%), the majority within six months of imaging. In bivariate analysis, cortical erosion on imaging and age above 63 years were each associated with fracture occurrence. In multivariate logistic regression, expansile lesions with cortical erosion were the strongest predictor of fracture (OR 2.1), though the confidence interval was wide (0.8–5.7), reflecting uncertainty in the estimate given the sample size.
The study's limitations are worth noting. 121 patients is a modest cohort for a logistic regression analysis with multiple predictors, and the wide confidence interval around the main finding means the true effect size is uncertain. Radiotracer uptake was assessed qualitatively rather than quantitatively, which limits reproducibility across readers and centers.
The findings suggest 99mTc-MIBI may add functional information about lesion metabolic activity to complement structural findings on conventional imaging — potentially useful in settings where MRI and PET/CT are not available — but prospective validation in larger cohorts with standardized protocols would be needed before it could inform fracture risk stratification in routine practice.
"Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1"
Source
James E. Hoffman, Naresh Bumma, Joshua Richter, Madhav V. Dhodapkar, Hans C. Lee, Attaya Suvannasankha, Jeffrey A. Zonder, Joseph J. Maly, Mansi R. Shah, Rachid Baz, Timothy J. Inocencio, Michelle DeVeaux, Cristina Ivanescu, Karen Rodriguez Lorenc, Glenn S. Kroog, Katherine Knorr, Lei Chi, James Harnett, Qiufei Ma, Sundar Jagannath, Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1, Blood Neoplasia, 2026, 100225, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2026.100225. March 27, 2026.
Overview
Clinical response rates and survival are the primary endpoints in myeloma trials, but how patients feel during treatment matters independently. This analysis examined patient-reported quality of life data from 117 participants in the LINKER-MM1 trial, which tested the BCMA×CD3 bispecific antibody linvoseltamab in relapsed or refractory myeloma over a median follow-up of 21.3 months.
Patients completed three validated questionnaires — the EORTC QLQ-C30 (general cancer quality of life), the QLQ-MY20 (myeloma-specific symptoms and impacts), and the EQ-5D-3L (health status) — at baseline, week 4, and then every four weeks. Changes from baseline were analyzed using mixed models for repeated measures, and clinically meaningful change thresholds were applied based on published literature.
Across the full cohort, statistically significant improvements from baseline were observed on all QLQ-C30 and QLQ-MY20 scales and on the EQ-5D visual analog scale. Improvements in global health status, fatigue, and pain appeared by week 16 and were maintained at most subsequent assessments. Pain improvement crossed the clinically meaningful threshold at week 20 and was generally sustained through week 104.
The pattern differed by response status. Among the 83 patients who achieved at least a partial response, significant improvements were seen across all scales. Among the 34 patients who did not respond, most scales showed numerical worsening. The alignment between clinical response and patient-reported outcomes suggests that the quality-of-life improvements reflect genuine disease control rather than a treatment effect independent of tumor response.
The findings support that linvoseltamab's efficacy translates into patient-perceptible benefit in heavily pretreated myeloma, sustained over two years of follow-up.
"Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma"
Source
Peter A Forsberg, Jacqueline A. Turner, Marita Meyer, Diana Abbott, Sara Nicholson, Henning Schade, Jeffrey V. Matous, Tara Gregory; Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma. Blood Adv 2026; bloodadvances.2025018639. doi: https://doi.org/10.1182/bloodadvances.2025018639 March 27, 2026.
Overview
Cilta-cel is a BCMA-directed CAR-T therapy approved for relapsed or refractory myeloma. A subset of patients develop unusual neurological events after treatment that are distinct from the better-characterized ICANS toxicity. This single-center study examined whether elevated absolute lymphocyte count (ALC) after cilta-cel infusion predicted those events, and whether prophylactic dexamethasone in high-ALC patients could reduce risk.
53 patients received cilta-cel at the Colorado Blood Cancer Institute between September 2023 and January 2025. The cohort was divided into two groups based on treatment period. In the pre-intervention group (30 patients, September 2023 to July 2024), no specific protocol addressed elevated ALC. In the intervention group (23 patients, August 2024 to January 2025), patients whose ALC exceeded 5,000/µL received three days of dexamethasone prophylaxis when that threshold was first identified.
In the pre-intervention group, 9 of 30 patients had peak ALC above 5,000/µL. Five of those nine (56%) developed atypical neurological events, and all five died from post-cilta-cel-related complications. In the intervention group, 7 of 23 patients exceeded the ALC threshold and received dexamethasone. One of the seven developed an atypical neurological event, and one patient died — from an infectious complication nine months after treatment, not from neurological toxicity.
Across the full cohort, ALC above 5,000/µL was associated with a 6.8-fold higher odds of atypical neurological events and a 6.2-fold higher risk of death compared to patients with ALC at or below that threshold. Overall survival was significantly worse in pre-intervention patients with high ALC than in both intervention patients with high ALC and patients with low ALC regardless of group.
Dexamethasone produced rapid ALC reduction in treated patients. The findings are limited by small numbers and the non-randomized before-after design, but the magnitude of the difference between groups suggests ALC monitoring and prophylactic dexamethasone warrant prospective evaluation in larger cohorts.
"Idecabtagene vicleucel manufacturing and clinical value of out of specification products in relapsed and refractory MM"
Source
Surbhi Sidana, Yi Lin, Andrew J Cowan, Paula Rodriguez-Otero, Christof Scheid, Peter J Mueller, Connor Broussard, Peter W Krengel, Yun Li, Romain Piault, Amy Corrao, Christine Ho, Krina K. Patel; Idecabtagene vicleucel manufacturing and clinical value of out of specification products in relapsed and refractory MM. Blood Adv 2026; bloodadvances.2025017186. doi: https://doi.org/10.1182/bloodadvances.2025017186 March 27, 2026.
Overview
Ide-cel is a BCMA-directed CAR-T therapy for relapsed or refractory myeloma. Like all CAR-T products, it requires a manufacturing process that can occasionally produce cells that fall outside commercial release specifications — for example, due to high activation markers or insufficient cell dose. This analysis examined ide-cel manufacturing performance over three years in the US and evaluated outcomes in patients who received out-of-specification product through an expanded access protocol.
Manufacturing data covered patients who underwent T cell collection for ide-cel between February 2021 and November 2024. The manufacturing success rate — the proportion of collections resulting in a product meeting commercial release criteria — improved from 95.3% in 2021 to 96.8% in 2024. Turnaround time from collection to delivery fell from 31 days to 24 days over the same period.
94 patients whose ide-cel did not meet commercial specifications were enrolled in the expanded access study (BB2121-EAP-001). The most common reasons for out-of-specification status were high CD137 activation or insufficient infused cell dose. Among the 94 patients, cytokine release syndrome occurred in 72%, nearly all grade 1 or 2. Neurological toxicities occurred in 16%, with two grade 3 events and the remainder grade 1 or 2.
Overall response rate in out-of-specification recipients was 75% and complete response rate was 35% — results comparable to those reported in trials using standard commercial product.
The findings indicate that ide-cel manufacturing is reliable and improving in both success rate and speed, and that patients who receive out-of-specification product achieve similar efficacy and safety outcomes to those who receive standard product, supporting the use of expanded access protocols when commercial release criteria are not met.
"FDG-PET Medullary Total Tumor Volume Highlights High-Risk Newly Diagnosed Multiple Myeloma Patients in CASSIOPEIA Trial"
Source
Jamet Bastien, Shamimeh Ahrari, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clement Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Diana Mateus, Philippe Moreau, Cyrille Touzeau, Françoise Kraeber-Bodere, Thomas Carlier; FDG-PET Medullary Total Tumor Volume Highlights High-Risk Newly Diagnosed Multiple Myeloma Patients in CASSIOPEIA Trial. Blood Adv 2026; bloodadvances.2025019465. doi: https://doi.org/10.1182/bloodadvances.2025019465 March 27, 2026. .
Overview
Standard risk stratification in myeloma relies on blood tests and genetic markers combined in the R-ISS staging system. PET/CT scans are used for diagnosis and response assessment, but whether quantitative measurements from those scans add prognostic information beyond R-ISS has not been fully established. This study examined that question in 195 newly diagnosed myeloma patients enrolled in CASSIOPET, a companion imaging study to the CASSIOPEIA trial, all treated with daratumumab-based induction and consolidation.
The imaging measurement evaluated was medullary total metabolic tumor volume (mTMTV) — the total volume of metabolically active myeloma within the bone marrow, calculated automatically using CT-based bone and liver segmentation applied to baseline PET images. The threshold for defining active disease was set using the median liver background signal, capturing both focal lesions and diffuse marrow involvement. 81% of patients had a positive PET scan at baseline.
In multivariate Cox regression, mTMTV was an independent predictor of both progression-free survival (p < 0.001) and overall survival (p < 0.001), after accounting for R-ISS. R-ISS also remained independently prognostic, with the two measures providing complementary rather than redundant information. A machine learning model confirmed mTMTV as the most informative single feature for both endpoints, with C-index values of 0.61 for progression-free survival and 0.66 for overall survival. Adding R-ISS, maximum bone marrow PET uptake, and anemia to mTMTV explained more than 60% of the machine learning model's predictions for progression-free survival; R-ISS, number of focal lesions, and maximum bone marrow uptake contributed similarly for overall survival.
Combining mTMTV with R-ISS allowed patients to be divided into two risk subgroups with meaningfully different outcomes.
The findings support incorporating quantitative PET measurements — specifically mTMTV — into baseline risk assessment for newly diagnosed myeloma patients receiving anti-CD38-based treatment, where they refine prognosis beyond what R-ISS alone provides.
"Low Dose Tocilizumab for Mitigation of Cytokine Release Syndrome with T-Cell Engaging Bispecific Antibodies"
Source
Issam S. Hamadeh, Maximillian Merz, Andriy Derkach, Lisa Modelevsky, Alexander M. Lesokhin, Sham Mailankody, Malin L. Hultcrantz, Carlyn R. Tan, Hani Hassoun, Urvi A. Shah, Kylee Maclachlan, Sridevi Rajeeve, Hamza Hashmi, Francesco Maura, Ross S. Firestone, Alice X. Wang, Anjali Amin, Dhwani Patel, Michael Scordo, Gunjan L. Shah, Heather J. Landau, Sergio Giralt, Saad Z. Usmani, Neha Korde, Low Dose Tocilizumab for Mitigation of Cytokine Release Syndrome with T-Cell Engaging Bispecific Antibodies, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.016. March 27, 2026.
Overview
Cytokine release syndrome is the most common early side effect when starting bispecific antibody treatment for myeloma, occurring most frequently during the step-up dosing phase. A single prophylactic dose of tocilizumab — an IL-6 receptor blocker — at 8 mg/kg before the first step-up dose has been shown to reduce CRS incidence. This study tested whether a lower dose of 4 mg/kg (half the standard prophylactic dose) is also effective.
90 patients with relapsed or refractory myeloma were included: 56 who received prophylactic tocilizumab at 4 mg/kg before the first step-up dose, and 34 historical controls who received no prophylaxis. CRS rates were compared between the two groups.
CRS occurred in 21% of patients who received low-dose tocilizumab prophylaxis, compared to 55% in those who received none — a statistically significant difference (p = 0.009). Grade 2 CRS, which typically requires active management, occurred in 2% of the prophylaxis group versus 21% in controls (p = 0.004). In multivariate logistic regression accounting for other patient characteristics, low-dose tocilizumab was associated with an 80% reduction in the odds of CRS (OR 0.20, 95% CI 0.06–0.65).
The retrospective design and use of a historical control group are the primary limitations. Differences in patient characteristics or bispecific antibody products between the two cohorts could influence the comparison, and prospective randomized data would be needed to confirm these findings. The results nonetheless suggest that 4 mg/kg tocilizumab given once before the first step-up dose reduces both the incidence and severity of CRS, at a dose that would also lower drug costs compared to the standard 8 mg/kg approach.
"Prognostic Effect of Sarcopenia and Nutritional Factors on Survival in Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Exploratory Study"
Source
X.Shen, J.Yu, X.Cheng, et al., “Prognostic Effect of Sarcopenia and Nutritional Factors on Survival in Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Exploratory Study,” Journal of Cachexia, Sarcopenia and Muscle17, no. 2 (2026): e70271, https://doi.org/10.1002/jcsm.70271. March 28, 2026.
Overview
Patients with myeloma vary considerably in their physical reserve and nutritional status at diagnosis, and those differences may influence how well they tolerate treatment and how long they survive. This retrospective study examined three measures of physical and nutritional status — sarcopenia (low muscle mass), the Prognostic Nutritional Index (PNI), and the Controlling Nutritional Status (CONUT) score — in 214 newly diagnosed myeloma patients treated at a single Chinese center between 2016 and 2022.
Muscle mass was measured from CT images taken at diagnosis and normalized for height to produce a skeletal muscle index. Patients below the threshold were classified as sarcopenic. PNI and CONUT scores were calculated from routine blood tests including albumin and lymphocyte counts.
37% of patients had sarcopenia at diagnosis. It was more prevalent in women, patients over 65, and those with BMI at or below 24 kg/m². Sarcopenic patients had shorter progression-free survival and substantially shorter overall survival than those without sarcopenia. In multivariate Cox regression, sarcopenia was an independent predictor of shorter overall survival (HR 2.75, 95% CI 1.50–5.05) after accounting for other prognostic factors.
Low PNI and high CONUT score — both indicating poorer nutritional status — were each associated with worse progression-free and overall survival. A combined model incorporating all three measures identified a gradient of risk: patients with sarcopenia, low PNI, and high CONUT score simultaneously had the worst outcomes of any subgroup.
The findings are limited by the retrospective single-center design and the patient population studied, which may not generalize to other settings. They suggest that measuring muscle mass and nutritional markers at diagnosis — all obtainable from imaging and blood tests already performed in routine care — could add prognostically useful information alongside standard disease staging.
"Malignant transformation in patients with monoclonal gammopathy of undetermined significance treated with teriparatide for osteoporosis: a bicenter retrospective study and analysis of the French national pharmacovigilance database"
Source
Cassez, R., Cortet, B., Bouvard, B. et al. Malignant transformation in patients with monoclonal gammopathy of undetermined significance treated with teriparatide for osteoporosis: a bicenter retrospective study and analysis of the French national pharmacovigilance database. Arch Osteoporos 21, 59 (2026). https://doi.org/10.1007/s11657-026-01693-x March 29, 2026.
Overview
Teriparatide is one of the few drugs that actively builds bone, making it valuable for patients with severe osteoporosis. Many of those patients also have MGUS — a plasma cell abnormality that is common in older adults and is itself a risk factor for fractures. Because MGUS can progress to myeloma or other blood cancers, some clinicians avoid teriparatide in this group out of concern that stimulating bone cell activity might also accelerate plasma cell growth. This retrospective study examined whether that concern is supported by evidence.
29 patients with osteoporosis and confirmed MGUS at the time of teriparatide initiation were followed at two French university hospitals between 2016 and 2022. Mean age was 73 years; 69% were women. Most had significant other health conditions. MGUS was IgG type in 55% and IgM type in 41%. Mean follow-up from teriparatide initiation was 60 months.
Two patients developed a hematologic malignancy during follow-up: one developed myeloma seven years after starting teriparatide, and one developed Waldenström's macroglobulinemia 21 months after initiation. Both had intermediate-risk MGUS at baseline. No other malignant progressions occurred. Teriparatide was stopped early in 17% of patients, most commonly for reasons unrelated to hematologic concerns.
A review of the French national pharmacovigilance database over the same period identified two additional hematologic malignancy reports associated with teriparatide, only one of which occurred in a patient with pre-existing MGUS.
The study is small and retrospective, and two progressions in 29 patients over five years cannot be meaningfully compared to expected progression rates without a matched control group not receiving teriparatide. The findings do not establish safety but provide early reassuring data that malignant transformation was uncommon. The authors suggest teriparatide can be considered in selected patients with severe osteoporosis and MGUS, with close hematologic monitoring during treatment
"Functional genomics studies identify determinants of response vs. resistance to pharmacological inhibitors of RAS in multiple myeloma"
Source
Arnold Bolomsky, Torsten Steinbrunn, Omar Al-Odat, Ricardo de Matos Simoes, Ryosuke Shirasaki, Oliver Bohorquez, Olga Dashevsky, Eleni Anastasakou, James G. Christensen, Andrew Aguirre, Ryan Young, Constantine S. Mitsiades; Abstract B027: Functional genomics studies identify determinants of response vs. resistance to pharmacological inhibitors of RAS in multiple myeloma. Cancer Res 1 March 2026; 86 (5_Supplement_1): B027. https://doi.org/10.1158/1538-7445.RASONCOTHER26-B027 .
Overview
RAS mutations, primarily in KRAS and NRAS, are present in up to 50% of myeloma cases. Drugs that inhibit mutant KRAS have shown activity in solid tumors, and similar agents are being developed for blood cancers. This study used preclinical myeloma models to systematically map which genetic and non-genetic factors determine whether myeloma cells respond to or resist RAS inhibition — information that may inform how these drugs are eventually used clinically.
Four inhibitors were tested: two mutant-selective KRAS inhibitors (MRTX-1257 targeting G12C and MRTX-1133 targeting G12D), a broader mutant-KRAS inhibitor (BI-2865), and a pan-RAS tricomplex inhibitor (RMC-6236). Human myeloma cell lines responded to all four at concentrations comparable to those achieved in solid tumor patients. RMC-6236 showed activity across both K/NRAS-mutant and wildtype lines that had other upstream RAS-activating alterations.
In mouse models, mutant-selective inhibitors produced initial responses against myeloma lesions, but tumors eventually escaped. When relapsed tumor cells were harvested and tested in the laboratory, they responded similarly to inhibitor-naive cells — suggesting resistance was not driven by stable genetic changes selected during treatment. DNA barcoding confirmed no significant enrichment of specific cell clones in inhibitor-treated mice, pointing toward non-genomic adaptation as a primary escape mechanism in that setting.
The bone marrow environment also influenced drug sensitivity. Co-culturing human myeloma lines with bone marrow stromal cells reduced their response to G12C inhibitors. In a mouse myeloma model with an NRAS mutation, IL-6 — a cytokine abundant in the myeloma bone marrow — attenuated the effect of RMC-6236.
To systematically identify genetic determinants of resistance, the researchers conducted 36 genome-scale CRISPR screens across 10 myeloma cell lines, using both gene knockout and gene activation approaches. The results revealed that resistance mechanisms are heterogeneous — different cell lines showed different vulnerabilities and resistance pathways. Recurrent resistance mechanisms included activation of upstream receptor signaling, amplification of RAS-MAPK pathway components, and loss of negative regulators of RAS-MAPK, NFκB, or PI3K/Akt signaling. Some resistance genes were shared across all three classes of RAS inhibitors; others were specific to individual agents, including PPIA as a distinct hit for RMC-6236.
Many of the resistance genes identified overlap with those found in equivalent CRISPR screens in solid tumors, while others appear specific to myeloma. Notably, the genes most differentially expressed after RAS inhibitor treatment were largely different from the top CRISPR screen hits in the same cell lines — a finding the authors use to argue that gene expression changes alone are insufficient to predict functional resistance mechanisms.
The study maps the landscape of RAS inhibitor resistance in myeloma at a level of detail that has not previously been available, and identifies both shared and cell-line-specific vulnerabilities that may inform patient selection and combination strategies in future clinical trials.
"The novel retinoid WYC-209 sensitizes multiple myeloma to carfilzomib via epigenetically upregulating ZMYND8"
Source
Xu, J., Yan, J., Zhang, H. et al. The novel retinoid WYC-209 sensitizes multiple myeloma to carfilzomib via epigenetically upregulating ZMYND8. Exp Hematol Oncol 15, 37 (2026). https://doi.org/10.1186/s40164-026-00770-8 March 30, 2026.
Overview
Carfilzomib is a proteasome inhibitor used in relapsed myeloma, but many patients develop resistance or have insufficient responses. Prior research identified that higher expression of a gene called ZMYND8 makes myeloma cells more sensitive to carfilzomib. This study tested whether a drug could increase ZMYND8 expression and whether doing so would enhance carfilzomib's effectiveness.
The researchers screened retinoic acid compounds — a class known to influence gene expression through epigenetic mechanisms — and identified a novel analog called WYC-209 as an activator of ZMYND8. Both WYC-209 and all-trans retinoic acid (ATRA, a naturally occurring retinoic acid) increased ZMYND8 expression in myeloma cells by promoting histone H3K27 acetylation at the ZMYND8 gene — an epigenetic mark associated with active transcription.
When combined with carfilzomib in laboratory experiments, both ATRA and WYC-209 produced synergistic killing of primary myeloma cells. WYC-209 combined with carfilzomib reduced cell viability, increased apoptosis, and caused visible dilation of the endoplasmic reticulum — a sign of increased protein stress consistent with proteasome inhibitor activity. When ZMYND8 was depleted from the cells, these effects were substantially reduced, confirming that ZMYND8 upregulation was responsible for the sensitization rather than an off-target effect of WYC-209.
In NSG mice carrying myeloma tumors, WYC-209 combined with carfilzomib reduced tumor burden more than carfilzomib alone, with ZMYND8 upregulation confirmed in the treated tumors.
The work was conducted in cell models and mice. Clinical testing has not yet been done. The findings identify ZMYND8 activation through retinoid compounds as a potential strategy for improving carfilzomib responses in myeloma patients.
"CLO26-105: Gut Microbiota and Multiple Myeloma: A Systematic Review of Risk, Prognosis, and Therapeutic Implications"
Source
Pasnoor, D. S., Pagidiboina, H. C., Thota, A., Yedulapuram, S., Chovatiya, J., Agrawal, D., Kanagala, S. G., Jain, A., & Desai, R. (2026). CLO26-105: Gut Microbiota and Multiple Myeloma: A Systematic Review of Risk, Prognosis, and Therapeutic Implications. Journal of the National Comprehensive Cancer Network, 24(3.5), Article CLO26-105, CLO26-105. Retrieved Mar 31, 2026, from https://doi.org/10.6004/jnccn.2025.7191
Overview
The trillions of bacteria living in the gut influence immune function, metabolism, and inflammation in ways that may affect cancer risk and treatment response. This systematic review synthesized findings from 17 human and animal studies examining whether gut microbiota composition is associated with myeloma risk, progression, prognosis, and treatment outcomes.
Several bacterial species showed consistent associations across studies. Mendelian randomization analyses — which use genetic variants as proxies for bacterial abundance to reduce confounding — identified Eubacterium ruminantium as positively associated with myeloma risk, while Akkermansia, Dorea, and Ruminococcaceae UCG014 correlated with lower risk.
Mechanistic studies pointed to specific pathways. Bacteria involved in nitrogen recycling, including Klebsiella and Streptococcus species, were implicated in glutamine-driven tumor growth. Citrobacter freundii, which produces ammonia, correlated with relapse and bortezomib resistance in some analyses.
In patients who had received stem cell transplants, low bacterial diversity and depletion of bacteria that produce short-chain fatty acids were associated with relapse and shorter survival. Higher abundance of butyrate-producing bacteria was consistently associated with better chances of achieving undetectable residual disease and longer survival across multiple studies.
In patients receiving CAR-T therapy, the presence of Flavonifractor and Sutterella predicted better outcomes, while higher Bifidobacterium abundance correlated with more severe cytokine release syndrome.
Animal models provided additional evidence of causality, showing that specific bacterial species can directly influence myeloma progression, immune responses, and drug resistance.
Interventions aimed at modifying the microbiome — including probiotics, dietary changes, and fecal microbiota transplantation — showed preliminary signals in some studies but none have been tested in adequately powered prospective trials.
The review is limited by substantial heterogeneity in how microbiome studies were conducted and reported across the 17 included papers, making direct comparisons difficult. The associations identified are promising but require prospective mechanistic studies before specific microbial targets can be translated into clinical recommendations.
"The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance"
Source
Baďurová, K., Kapustová, V., Kotulová, J. et al. The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance. Mol Diagn Ther (2026). https://doi.org/10.1007/s40291-026-00836-7 March 30, 2026.
Overview
Myeloma is driven by a complex and evolving set of genetic alterations that differ between patients and change over time within the same patient. Standard diagnostic tests — primarily FISH, which detects specific chromosomal abnormalities — capture only a fraction of the genomically relevant information now known to influence prognosis and treatment response. This review examined the current role of genomic diagnostics in myeloma and related plasma cell disorders, the technologies available, and the practical challenges of integrating more comprehensive testing into clinical practice.
The review mapped how the genetic landscape of myeloma evolves across disease stages — from MGUS through smoldering myeloma to active disease and relapse — and traced how risk stratification models have developed from clinical staging systems toward integrated genomic frameworks. Recent recommendations have moved toward quantifying cytogenetic abnormality burden rather than treating individual findings as binary present-or-absent markers, and toward incorporating tumor suppressor gene mutations alongside chromosomal changes.
The review compared six technology categories: FISH, targeted gene panels, whole-exome sequencing, whole-genome sequencing, long-read sequencing platforms, optical genome mapping, and circulating tumor DNA analysis. Each was evaluated for sensitivity, the types of alterations it detects, and where it fits in the diagnostic timeline — baseline workup, response monitoring, or resistance detection. FISH remains the practical standard but misses structural variants, copy number changes at low allele frequencies, and point mutations. Whole-genome sequencing captures the broadest range of alterations but generates data complexity and cost that limit routine use. Circulating tumor DNA from blood offers the prospect of non-invasive longitudinal monitoring without repeated bone marrow biopsies.
Practical barriers to broader genomic testing include cost, turnaround time, the need for bioinformatics infrastructure, and the absence of standardized reporting frameworks that translate genomic findings into actionable clinical decisions. The review proposes a framework for proactively incorporating newer approaches — starting with technologies that add the most clinically actionable information beyond current standard testing and building infrastructure for longitudinal monitoring as response-adapted treatment becomes more common.
"Renal recovery and clinical outcomes with daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma with severe renal impairment"
Source
Horigome, Y., Kamata, H., Ehata, K. et al. Renal recovery and clinical outcomes with daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma with severe renal impairment. Int J Hematol (2026). https://doi.org/10.1007/s12185-026-04205-2 March 30, 2026.
Overview
Kidney impairment affects a significant proportion of newly diagnosed myeloma patients and is associated with early complications and worse survival. The MAIA trial established daratumumab, lenalidomide, and dexamethasone (DRd) as a standard frontline regimen for transplant-ineligible patients, but excluded those with creatinine clearance at or below 30 mL/min — precisely the group with the most severe kidney dysfunction. Evidence for DRd in that population is therefore limited to small observational series.
This retrospective analysis included 10 transplant-ineligible newly diagnosed myeloma patients with an estimated glomerular filtration rate (eGFR) at or below 30 mL/min/1.73 m² treated with frontline DRd at a single institution between 2019 and 2024. All 10 were classified as ISS stage III by the second revision criteria.
The overall hematologic response rate was 80%. Half of patients achieved very good partial response or better. Complete renal response — defined as sustained recovery of kidney function — occurred in 40% of patients and was associated with deeper hematologic responses and longer progression-free survival and time to next treatment. Median eGFR improved from 21 to 50.5 mL/min/1.73 m² across the cohort.
The study is limited by its small size and retrospective single-center design, and no conclusions about comparative effectiveness can be drawn without a control group. Lenalidomide dosing in severe renal impairment requires careful adjustment, and the feasibility demonstrated here reflects practice at a specialized center. The findings nonetheless suggest DRd can be used in this excluded population with meaningful rates of both disease response and kidney recovery, supporting prospective evaluation in larger cohorts.
"Revised criteria for light chain MGUS enhance diagnostic accuracy and risk stratification"
Source
Andersen, L.S., Mæng, C.V., Rögnvaldsson, S. et al. Revised criteria for light chain MGUS enhance diagnostic accuracy and risk stratification. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01478-y March 30, 2026.
Overview
Light chain MGUS (LC-MGUS) is a precursor condition defined by abnormal free light chain levels in the blood without other evidence of plasma cell disease. It requires monitoring because a small proportion of people with it progress to myeloma or related disorders. The reference intervals used to define "abnormal" free light chain levels have recently been revised by the iStopMM study group, based on updated population data. This study tested whether those revised criteria perform well in a real clinical cohort.
Researchers identified 360 individuals classified as having LC-MGUS by the original criteria from the Danish DALY-CARE data resource, all of whom had Freelite free light chain measurements available. Applying the revised iStopMM criteria, 215 of the 360 were still classified as LC-MGUS, while 150 (40%) were reclassified as having normal free light chain levels.
Among the 215 who retained an LC-MGUS diagnosis under the revised criteria, 21 (10%) progressed to a related disorder — 11 to myeloma and seven to AL amyloidosis. The two-year cumulative progression risk was 5.8% and the five-year risk was 8.9%, with an annual progression rate of 3%.
Among the 150 reclassified as normal, only two individuals (1.3%) progressed, and neither progressed to myeloma or AL amyloidosis.
The findings validate the revised criteria in a clinical setting. Adopting them would reduce LC-MGUS diagnoses by 40% without missing any cases that go on to develop the most clinically significant outcomes. That reduction has practical implications: fewer people would require long-term hematology monitoring for a condition that, under the original criteria, was assigned to many who were not genuinely at elevated risk.
"Treatment-Specific Prediction Models in Multiple Myeloma: A Critical Review of Current Evidence and Future Directions"
Source
M. M.Jarrah, H. O.Al-Shamsi, Z.Abuhelwa, et al., “Treatment-Specific Prediction Models in Multiple Myeloma: A Critical Review of Current Evidence and Future Directions,” European Journal of Haematology (2026): 1–17, https://doi.org/10.1111/ejh.70177. March 30, 2026.
Overview
Choosing between myeloma treatments requires estimating not just how a patient is likely to do in general, but how they are likely to respond to a specific drug combination. General prognostic tools — which predict outcomes regardless of treatment — are common in myeloma, but models that estimate benefit or toxicity conditional on a particular regimen are scarce. This review searched PubMed, Embase, and Scopus for prediction models built within a specific treatment framework and identified 13 that met inclusion criteria.
Ten of the 13 models predicted therapeutic outcomes and three predicted toxicity. Treatments covered included bortezomib-based induction, daratumumab-containing combinations, ixazomib-based triplets, and CAR-T therapy. Most models used standard blood tests and clinical variables as predictors; few incorporated cytogenetic data and none included patient-reported outcomes.
Traditional regression methods dominated; machine learning was used in a small number. External validation — testing the model in a patient population separate from the one used to build it — was performed in seven of the 13 studies. Calibration, which measures whether predicted probabilities match observed outcomes, was inconsistently reported. Decision curve analysis, which quantifies whether a model's predictions would actually improve clinical decisions, was included in only two studies.
Several specific gaps stand out. None of the models incorporated imaging data such as PET/CT metabolic burden or MRI marrow infiltration patterns, despite their established prognostic relevance. No model integrated advanced genomic profiling beyond standard cytogenetics. No model included frailty measures in a treatment-specific context, despite older adults representing a large share of myeloma patients and having distinct toxicity profiles. Only two models used longitudinal biomarker data collected during treatment rather than relying solely on values at diagnosis.
A practical barrier limits the reach of all 13 models: none has been implemented as an online calculator, clinical decision-support tool, or mobile application. Models that exist only in published equations or require machine learning expertise to run cannot be used at the bedside.
The review identifies a path forward: treatment-specific models that incorporate cytogenetics, imaging, patient-reported outcomes, frailty measures, and on-treatment biomarker changes, validated externally in independent cohorts, evaluated using decision curve analysis, and made available through accessible digital interfaces. Until those gaps are addressed, the models identified in this review remain research outputs rather than clinical tools.
"Management of hematological toxicities after BCMA-directed CAR-T cell therapy"
Source
Cook, J., Gupta, S., Abdallah, N. et al. Management of hematological toxicities after BCMA-directed CAR-T cell therapy. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01455-5 March 30, 2026.
Overview
Low blood counts after CAR-T therapy — affecting red cells, platelets, and white cells — are common and can lead to transfusions, infections, and prolonged hospital stays. The CAR-HEMATOTOX (CAR-HT) score uses pre-treatment blood values to estimate hematotoxicity risk before infusion. This study examined whether the score predicts the severity of blood count problems and the supportive care interventions needed in 224 myeloma patients treated with BCMA-directed CAR-T therapy between 2016 and 2024.
58% of patients had a high CAR-HT score (2 or above). Compared to low-score patients, high-score patients had higher rates of grade 3 immune effector cell-associated hematotoxicity (45% versus 23%) and grade 4 events (5% versus 1%). Severe anemia occurred in 43% versus 24% and severe thrombocytopenia in 51% versus 28%. High-score patients were seven times more likely to require red cell or platelet transfusions.
Growth factor support — G-CSF for white cell counts and thrombopoietin receptor agonists for platelets — was used variably and showed inconsistent effectiveness. Stem cell boosts, used in 4% of patients, produced rapid recovery across all three blood cell lineages. Infections were more frequent in high-score patients and in those who received more intensive cytopenia-directed interventions, suggesting that the interventions themselves may carry infection risk.
Despite the differences in blood count complications and supportive care burden, progression-free and overall survival did not differ significantly between high and low CAR-HT groups. Cytopenia-directed interventions did not affect survival outcomes.
The findings support using the CAR-HT score before CAR-T infusion to identify patients who will need more intensive monitoring and supportive care, particularly transfusion planning and earlier consideration of stem cell boost, without implying that managing cytopenias more aggressively improves survival.
"Baseline absolute lymphocyte count, C-reactive protein, and ferritin predict CAR T cell-related toxicities and outcomes in multiple myeloma"
Source
Pan, D., Mouhieddine, T.H., Sheng, T. et al. Baseline absolute lymphocyte count, C-reactive protein, and ferritin predict CAR T cell-related toxicities and outcomes in multiple myeloma. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02831-2 March 30, 2026.
Overview
CAR-T therapy produces highly variable outcomes in relapsed and refractory myeloma — some patients achieve deep, durable remissions while others relapse quickly or experience serious toxicities. Better tools for predicting those outcomes before treatment would help clinicians counsel patients and plan supportive care. This single-center retrospective study examined whether standard blood tests measuring baseline inflammation could serve that purpose.
Researchers analyzed myeloma patients who received CAR-T therapy — either commercial products or investigational agents on clinical trials — at Mount Sinai Hospital between 2017 and 2023. Patients were included if they were at least three months post-infusion at the data cutoff. Baseline laboratory values reflecting inflammatory status were collected alongside demographics, disease characteristics, CAR-T product type, and clinical outcomes including toxicity and response.
The rationale for focusing on inflammatory markers is mechanistic: the interaction between infused CAR-T cells and the patient's existing immune environment influences how the cells activate, expand, and persist, as well as the severity of cytokine release syndrome and other inflammatory toxicities. Markers such as C-reactive protein, ferritin, lactate dehydrogenase, and lymphocyte counts are already measured as part of routine pre-treatment workups and require no additional testing.
The full results of the analysis — which specific markers predicted which outcomes, and with what magnitude of effect — are reported in the complete paper. The study was approved by the Mount Sinai institutional review board with a waiver of informed consent given its retrospective design.
"Clinical outcomes and risk factors of cytomegalovirus reactivation in teclistamab-treated multiple myeloma patients"
Source
Cheema, H., Shrestha, A., Naqvi, S. et al. Clinical outcomes and risk factors of cytomegalovirus reactivation in teclistamab-treated multiple myeloma patients. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01484-0 March 31, 2026.
Overview
Teclistamab suppresses immune function as part of its mechanism, raising concern about reactivation of latent viruses including cytomegalovirus (CMV). CMV reactivation can range from asymptomatic to severe organ damage in immunocompromised patients, but how often it occurs in myeloma patients receiving teclistamab and what clinical consequences it carries have not been well characterized. This retrospective study examined 177 myeloma patients treated with teclistamab between December 2022 and December 2024.
CMV testing was performed in 173 of the 177 patients (98%). Reactivation occurred in 38 patients (22%), with a median initial viral load of 87 IU/mL. The median peak viral load across all reactivations was 288 IU/mL, though values ranged up to 20,000 IU/mL in individual patients. 90% of reactivations were asymptomatic. Four patients had symptomatic disease; three required antiviral treatment. No patients developed end-organ damage. Eight patients (21% of those who reactivated) experienced a second reactivation episode.
In multivariable logistic regression, prior CMV reactivation was the only significant independent predictor of reactivation during teclistamab treatment (odds ratio 3.34, p = 0.005). CMV reactivation did not affect overall survival. Prophylactic intravenous immunoglobulin use was associated with better survival (hazard ratio 0.49, p = 0.011), consistent with the broader benefit of immunoglobulin replacement in patients with treatment-related hypogammaglobulinemia.
The findings suggest that CMV reactivation affects roughly one in five teclistamab-treated patients but is typically low-level and asymptomatic. A prior history of CMV reactivation identifies patients at higher risk and may warrant more frequent monitoring, while universal prophylaxis does not appear necessary based on these data.
"Sustained IL-15 Release Enhances CAR-T Therapy in Multiple Myeloma via FOXO1 Signaling Axis Activation"
Source
Kuai Yu, Yunxin Zeng, Bo Lu, Mei Xie, Yaqun Wang, Tiantian Sun, Xiaojun Xu, Yuanbin Song, Wei Xiao, Sustained IL-15 Release Enhances CAR-T Therapy in Multiple Myeloma via FOXO1 Signaling Axis Activation, Biomaterials, 2026, 124187, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2026.124187. March 31, 2026.
Overview
CAR-T therapy produces responses in myeloma but durability is limited — infused T cells often become exhausted or die before they can sustain long-term disease control. This study developed a nanoparticle system designed to deliver an immune-stimulating drug directly to myeloma lesions in a controlled way, with the goal of keeping CAR-T cells functional for longer.
The drug delivered was N-803, an engineered form of IL-15 that stimulates both T cells and natural killer cells. N-803 has shown promise as an immune activator but has short-lived effects and causes systemic side effects when given systemically. To address that, the researchers encapsulated it in a nanogel — a small gel particle that releases its contents specifically in low-oxygen environments. Because myeloma lesions in the bone marrow are hypoxic, the nanogel releases N-803 preferentially at tumor sites rather than distributing throughout the body.
The nanogel was also surface-modified with antibodies targeting two proteins: CD138, which is expressed on myeloma cells, and TIM-3, an inhibitory receptor expressed on exhausted T cells within the tumor environment. This dual targeting was designed to concentrate the nanogel both at tumor cells and at the exhausted T cells that need stimulation.
In laboratory experiments, the nanogel promoted CAR-T cell expansion and shifted the cells toward memory phenotypes — longer-lived subtypes that sustain immune surveillance over time — while reducing markers of exhaustion. Transcriptomic analysis identified the FOXO1 signaling pathway as the key mechanism driving that memory differentiation: N-803 activates a PI3K/Akt cascade that regulates FOXO1, which in turn controls genes involved in memory T cell development.
In animal models, CAR-T cells treated with the nanogel persisted longer, natural killer cell recruitment to tumors increased, and immunosuppressive cells within the tumor environment decreased. Tumor control was more durable than with CAR-T alone.
The work was conducted entirely in cell models and mice. Whether this approach translates to humans — and whether the manufacturing and delivery of such a system is feasible at clinical scale — remains to be established.
"Navigating the Post-BCMA/GPRC5D Landscape: Efficacy of Selinexor, Bortezomib, and Dexamethasone After Sequential Immunotherapy Failure in Penta-Refractory Multiple Myeloma—A Multicenter Analysis"
Source
M.Al-Bazaz, W.Alsdorf, L.Leypoldt, et al., “Navigating the Post-BCMA/GPRC5D Landscape: Efficacy of Selinexor, Bortezomib, and Dexamethasone After Sequential Immunotherapy Failure in Penta-Refractory Multiple Myeloma—A Multicenter Analysis,” American Journal of Hematology (2026): 1–7, https://doi.org/10.1002/ajh.70297. March 31, 2026.
Overview
Myeloma cells produce abnormally high levels of immunoglobulin, a process that generates reactive oxygen species (ROS) as a byproduct. Some compounds can kill myeloma cells by pushing ROS levels past a toxic threshold, triggering cell death. This study investigated a specific enzyme called PNPO — which plays a role in vitamin B6 metabolism — as a target in that process, and identified an existing drug that inhibits it.
The researchers found PNPO to be expressed at high levels in myeloma and in several other cancers. In myeloma, higher PNPO levels correlated with more advanced disease. Functional experiments showed PNPO promotes myeloma cell proliferation and stimulates the formation of osteoclasts — the cells responsible for bone destruction in myeloma — through signals carried by small vesicles called exosomes released by myeloma cells.
Using computational screening that targeted two critical residues on the PNPO protein (R95 and K117), the researchers identified hetrombopag — a drug approved for treating low platelet counts — as a potential PNPO inhibitor. In myeloma cell experiments, hetrombopag reduced both cell proliferation and osteoclast differentiation, consistent with PNPO inhibition.
Preliminary clinical data also showed an association between hetrombopag treatment and longer survival in myeloma patients, though the nature and size of that dataset are not detailed in the abstract.
The work identifies PNPO as a contributor to myeloma cell growth and bone destruction, and suggests that hetrombopag — already an approved drug — could be worth investigating as a myeloma treatment. Formal clinical evaluation in a myeloma-specific trial has not yet been reported.
"BIO26-048: A Meta-Analytic Evaluation of Efficacy and Safety Between Ide-cel and Cilta-cel in Relapsed/Refractory Multiple Myeloma Based on Clinical Trial and Real-World Data"
Source
Golmohammadi, M., Raza, S., Hansen, D. K., Dima, D., Khouri, J., Mazzoni, S., Faiman, B., Williams, L., Valent, J., Basali, D., Samaras, C., Anwer, F., & Jaberi-Douraki, M. (2026). BIO26-048: A Meta-Analytic Evaluation of Efficacy and Safety Between Ide-cel and Cilta-cel in Relapsed/Refractory Multiple Myeloma Based on Clinical Trial and Real-World Data. Journal of the National Comprehensive Cancer Network, 24(3.5), Article BIO26-048, BIO26-048. https://doi.org/10.6004/jnccn.2025.7251 March 31, 2026.
Overview
Both ide-cel and cilta-cel are BCMA-directed CAR-T therapies approved for relapsed or refractory myeloma, but they have not been compared in a randomized trial. This meta-analysis pooled data from 29 studies — 5,750 patients treated with ide-cel and 3,285 with cilta-cel — to compare response rates and adverse events between the two products.
Cilta-cel produced higher overall response rates and higher complete response rates than ide-cel, both differences statistically significant (p < 0.002 for each). The magnitude of those differences is not reported in the abstract but the direction was consistent across the included studies.
On the safety side, cilta-cel was associated with significantly higher rates of infections (p = 0.004), neurotoxicity (p = 0.004), delayed neurotoxicity (p < 0.001), and secondary primary malignancies (p = 0.026). The delayed neurotoxicity finding is particularly relevant given that cilta-cel has been associated with a distinct movement and neurocognitive disorder not seen with ide-cel in clinical trial data.
The meta-analysis used random-effects models to account for heterogeneity across studies, with sensitivity analyses and influence diagnostics applied. The primary limitation is that the comparison is indirect — patients enrolled in ide-cel and cilta-cel studies differ in baseline characteristics, prior treatment histories, and study designs in ways that statistical pooling cannot fully correct. The two products also have different CAR constructs, dosing schedules, and eligibility criteria, which contribute to outcome differences independently of any intrinsic efficacy difference.
The findings are consistent with the impression from individual trials that cilta-cel produces deeper responses, while carrying a higher burden of neurological and infectious toxicities that require specific monitoring strategies.
"Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol-Inspired Approach"
Source
T.Yu, C.Wang, J.Xie, et al., “Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol-Inspired Approach,” Basic & Clinical Pharmacology & Toxicology138, no. 5 (2026): e70227, https://doi.org/10.1111/bcpt.70227. March 31, 2026.
Overview
Patients whose myeloma has stopped responding to two proteasome inhibitors, two immunomodulatory drugs, an anti-CD38 antibody, and now both BCMA- and GPRC5D-directed immunotherapies have few remaining options. This retrospective multicenter analysis examined whether selinexor combined with bortezomib and dexamethasone (SVd) can produce responses in that population.
Eighteen patients treated at six German centers between December 2023 and October 2025 met the inclusion criteria. Median age was 63 years. Median prior lines of therapy were seven, administered over a median of 9.5 years from diagnosis. All had received prior autologous stem cell transplant. Half had active extramedullary disease — myeloma that had spread outside the bone marrow — at the start of SVd. One third had deletion of chromosome 17p, a high-risk genetic feature, including two with concurrent TP53 mutations. Prior BCMA-directed therapies included ide-cel, teclistamab, belantamab mafodotin, and cilta-cel in various combinations; all had also progressed on GPRC5D-targeted therapy.
The overall response rate was 61%, including one complete response, five very good partial responses, and five partial responses. Disease was controlled in 78% of patients. Median progression-free survival was 4.3 months. Responses occurred quickly — median time to first response was 0.9 months.
The extramedullary disease findings were particularly notable. Of the nine patients with active extramedullary lesions, four achieved complete or near-complete resolution on imaging, including regression of lesions ranging from 3.2 to 7.5 cm. In a disease context where extramedullary involvement typically predicts very poor outcomes with most available treatments, those responses stand out.
Among six patients with del(17p), four achieved meaningful disease control including two very good partial responses lasting up to ten months — suggesting selinexor's mechanism of retaining tumor suppressor proteins in the nucleus may partially counteract the effect of p53 pathway loss in heterozygous deletions.
Two patients who had previously failed CAR-T therapy with ide-cel were bridged to a second CAR-T product (cilta-cel) using SVd. Both achieved responses sufficient to proceed to the second CAR-T infusion. A third patient was bridged to T cell collection. This is clinically relevant given that alkylating agents commonly used as bridging therapy can impair T cell fitness and compromise CAR-T manufacturing.
Toxicity was consistent with known SVd effects. Thrombocytopenia occurred in 72% of patients, with grade 3 or 4 severity in 56%. Grade 3 or 4 anemia occurred in 50% and grade 3 or 4 neutropenia in 22%. Fatigue and nausea were common but almost entirely low-grade, with nausea well controlled using the protocol antiemetic regimen. No grade 3 or higher infections were recorded despite the severe immunosuppression in this population. No treatment-related deaths occurred.
The retrospective design, 18-patient sample, and heterogeneous prior treatment histories are the primary limitations. The cohort nonetheless represents real-world patients with aggressive disease features often excluded from trials, and the consistency of responses across sites adds confidence to the findings.
"HSR26-239: Outcomes in Multiple Myeloma Hospitalizations With CAR-T Therapies in the United States"
Source
Atodaria, K., Tetali, P., Kottapalli, N., Iqbal, S., Mandal, S., Zarrar, R., & Ashfaq, A. (2026). HSR26-239: Outcomes in Multiple Myeloma Hospitalizations With CAR-T Therapies in the United States. Journal of the National Comprehensive Cancer Network, 24(3.5), Article HSR26-239, HSR26-239. https://doi.org/10.6004/jnccn.2025.7311 March 31, 2026.
Overview
Ide-cel and cilta-cel were approved for relapsed or refractory myeloma in 2021 and 2022 based on results from the KarMMA and CARTITUDE trials. This analysis used the US National Inpatient Sample database to examine how toxicity rates observed in routine hospital practice compare to those reported in those trials, and to document the financial burden of CAR-T hospitalizations.
330 hospitalizations involving ide-cel were identified in 2021 and 2022, and 95 involving cilta-cel in 2022. Patients in the real-world data were older than those enrolled in the trials: median age was 67–68.5 years for ide-cel recipients and 66 for cilta-cel recipients, compared to 58–63 years across the trial cohorts.
For ide-cel, cytokine release syndrome occurred in 71% of real-world hospitalizations, compared to 84–88% in the KarMMA trials. ICANS occurred in 20%, compared to 15–18% in trials. For cilta-cel, CRS occurred in 47% in the real-world data, compared to 60–95% in the CARTITUDE trials, depending on the cohort. ICANS rates were similar at 21% in both real-world and trial settings.
In-hospital mortality was 1.5% for ide-cel; no in-hospital deaths were recorded for cilta-cel in 2022, though the cilta-cel sample was small. Median length of stay was 9–11 days for ide-cel and 13 days for cilta-cel. Median total hospitalization charges were $1.2–1.7 million for ide-cel and $1.2 million for cilta-cel.
The lower CRS rates in real-world practice compared to trials likely reflect a combination of factors: older, more diverse patient populations, evolving step-up dosing protocols, earlier recognition and treatment of CRS, and differences in monitoring intensity. The higher ICANS rate with ide-cel in real-world versus trial data warrants attention, though administrative database coding may affect how accurately these events are captured.
The hospitalization charges reported here reflect facility costs and do not include the drug acquisition cost itself, meaning total treatment costs are substantially higher than these figures suggest.
"Psoas and pectoralis muscle indices and brown adipose tissue activity may be prognostic indicators in older patients with multiple myeloma"
Source
Yilmaz Kars, M., Kars, T.U., Cayci, M. et al. Psoas and pectoralis muscle indices and brown adipose tissue activity may be prognostic indicators in older patients with multiple myeloma. Int J Hematol (2026). https://doi.org/10.1007/s12185-026-04206-1 March 31, 2026.
Overview
Changes in muscle mass and body fat distribution affect outcomes in several cancers, including myeloma. This retrospective study examined whether body composition measurements extracted from PET/CT scans — already performed as part of routine myeloma assessment — could predict disease progression and survival in 75 myeloma patients aged 60 or older treated between January 2023 and March 2025.
41% of patients received autologous stem cell transplant. Median progression-free survival was 6 months and median follow-up was 25.7 months.
Several factors predicted outcomes in multivariate analysis. Stem cell transplant was associated with reduced risk of disease progression (OR 0.26, p = 0.019) and a trend toward improved overall survival (OR 0.25, p = 0.060). Higher Charlson Comorbidity Index scores — a measure of overall disease burden from other health conditions — independently predicted higher mortality (OR 1.68, p = 0.017).
Among body composition measures, a lower pectoralis major index — a measure of chest muscle mass derived from PET/CT imaging — was independently associated with disease progression (OR 0.003, p = 0.012), suggesting that reduced muscle mass in this region predicts worse disease control.
Among the 41% of patients who received stem cell transplant, higher brown adipose tissue (BAT) activity on PET/CT — measured by mean standardized uptake value — correlated strongly with shorter post-transplant progression-free survival (rho = −0.717). Brown adipose tissue is metabolically active fat that generates heat; its activity on PET/CT is an incidental finding whose prognostic significance in myeloma has not been well studied.
The study is limited by small sample size, retrospective design, and a single-center population. The body composition measurements tested here are obtainable from standard PET/CT scans without additional procedures, which makes them potentially practical if validated in larger prospective cohorts.
"Clinical-Grade Armored BCMA CAR-T Cells Overcome TGF-β–Mediated Immunosuppression in Multiple Myeloma"
Source
Deepak Parashar, Katie Palen, Ansul Sharma, Swadha Pandey, Tyce Kearl, Peirong Hu, Peiman Hematti, Sabari Radhakrishnan, Fumou Sun, Siegfried Janz, Bryon Johnson, Dina Schneider, Nirav Shah, Binod Dhakal, Clinical-Grade Armored BCMA CAR-T Cells Overcome TGF-β–Mediated Immunosuppression in Multiple Myeloma, Blood Immunology & Cellular Therapy, 2026, 100048, ISSN 3050-5976, https://doi.org/10.1016/j.bict.2026.100048. March 31, 2026.
Overview
One reason CAR-T therapy loses effectiveness in myeloma over time is the immunosuppressive environment of the bone marrow. A signaling protein called TGF-β is abundant in that environment and directly suppresses T cell activity, contributing to exhaustion and treatment failure. This study tested whether blocking TGF-β signaling within the CAR-T cells themselves could improve their durability and effectiveness.
The researchers engineered BCMA-directed CAR-T cells to co-express a truncated, non-functional form of the TGF-β receptor called DNTGF-βRII. Because this receptor fragment cannot transmit TGF-β signals, cells expressing it become resistant to TGF-β-mediated suppression. The cells were also manufactured with IL-7 and IL-15, cytokines that support T cell survival and memory development, using the CliniMACS Prodigy platform — a closed, automated system compatible with clinical manufacturing standards.
The manufactured cells met all release criteria for patient dosing. When exposed to TGF-β1 in the laboratory, the armored cells showed reduced activation of the downstream suppressive signaling pathway (measured by pSmad2/3 levels) and less exhaustion than standard CAR-T cells, confirming that the resistance modification was functional. The cells retained strong cytotoxicity against primary myeloma cells that had prior BCMA exposure — relevant because BCMA expression can be reduced by prior BCMA-targeted treatment.
In mouse tumor models, armored CAR-T cells reduced or eliminated tumor burden, improved survival, and persisted in the animals longer than unmodified cells. Mice that cleared their tumors showed no disease recurrence when subsequently re-exposed to myeloma cells, suggesting the armored cells established durable immune memory.
The work was conducted in cell models and mice using a clinically compatible manufacturing process. Human studies have not yet been conducted.
"Mesoporous polydopamine-based biomimetic nanoplatform for immunotherapy of multiple myeloma by homologous targeting and systemic immune activation"
Source
Yonghua Li, Yang Gao, Zhifang Xiao, Wenfang Jiang, Na Han, Xianjun He, Ling Ouyang, Peng Zhang, Mesoporous polydopamine-based biomimetic nanoplatform for immunotherapy of multiple myeloma by homologous targeting and systemic immune activation, Biomaterials Advances, 2026, 214853, ISSN 2772-9508, https://doi.org/10.1016/j.bioadv.2026.214853. March 31, 2026.
Overview
Photothermal therapy uses near-infrared light to heat and destroy tumor cells. When combined with chemotherapy and immune activation in a single delivery system, the three mechanisms can work together at the tumor site. This study built and tested such a combined system for myeloma.
The nanoparticle was constructed from mesoporous polydopamine — a biodegradable, porous material — doped with manganese ions to improve its ability to convert near-infrared light into heat. The chemotherapy drug carfilzomib was loaded into the pores. The outer surface was coated with cell membrane material to improve biocompatibility and help the particles evade immune clearance before reaching the tumor.
Under near-infrared light exposure, the system releases carfilzomib and manganese ions in a controlled way at the tumor site while simultaneously generating heat. The three effects — direct drug-mediated cell death, heat-induced tumor destruction, and manganese-associated immune activation — were designed to reinforce each other.
In cell culture experiments, the coated nanoparticle system showed favorable biocompatibility. In a myeloma mouse model, the combination of the nanoparticle system with near-infrared irradiation produced greater tumor reduction than any component alone. Beyond direct tumor killing, the treatment stimulated dendritic cell maturation, activated CD3+ T cells, and increased infiltration of cytotoxic T lymphocytes into the tumor — changes consistent with conversion of a suppressive tumor environment into an immune-active one.
The work was conducted in cell models and mice. Significant technical and regulatory challenges remain before nanoparticle-based photothermal systems can be tested in humans, and no clinical data exist for this approach in myeloma.
"Development and multinational validation of a multiple myeloma–specific comorbidity index using real-world cohorts: CAREMM-2108"
Source
Choi, S., Byun, J.M., Oh, S.E. et al. Development and multinational validation of a multiple myeloma–specific comorbidity index using real-world cohorts: CAREMM-2108. Blood Cancer J. 16, 52 (2026). https://doi.org/10.1038/s41408-026-01475-1 March 31, 2026.
Overview
Standard comorbidity measures used in myeloma — including the Charlson Comorbidity Index and the version incorporated in the IMWG frailty score — were not designed for this disease and have modest predictive performance in real-world populations. This study developed and externally validated a myeloma-specific comorbidity index using claims and registry data from Korea and Japan.
The index was built using a nationwide Korean claims cohort of 17,273 myeloma patients diagnosed between 2007 and 2022. Eight variables were selected through multivariable Cox regression and weighted by their association with overall survival: male sex (1 point), age 60–69 (2 points), age 70–79 (4 points), age 80 or older (6 points), congestive heart failure (2 points), cerebrovascular disease (1 point), hepatic disease (1 point), and a history of other cancer (1 point).
The resulting score stratifies patients into four risk groups. Median overall survival was 72.5 months in the low-risk group (score 0–2), 43.8 months in intermediate-I (3–4), 30.9 months in intermediate-II (5), and 20.3 months in the high-risk group (6 or above).
External validation was performed in two independent cohorts — 1,473 Korean patients from a multicenter registry and 314 Japanese patients — and the index remained independently prognostic after adjusting for ECOG performance status, R2-ISS stage, and treatment intensity. Predictive performance measured by area under the ROC curve was 0.637 for the MM-CI, compared to 0.613 for the age-adjusted Charlson Comorbidity Index and 0.569 for the concise version used in the IMWG frailty score.
The score uses eight variables obtainable from routine administrative or clinical data without additional testing. Prospective validation in Western populations and in patients treated with more recent regimens including quadruplets and immunotherapies would strengthen its generalizability.
"Bridging therapy before CAR-T for multiple myeloma: a survey from the CMWP and CTIWP of the EBMT"
Source
Gagelmann, N., Merz, M., Baaij, L.G.A. et al. Bridging therapy before CAR-T for multiple myeloma: a survey from the CMWP and CTIWP of the EBMT. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02816-1 March 31, 2026.
Overview
When a myeloma patient is approved for CAR-T therapy, several weeks pass between T cell collection and infusion while the product is manufactured. Most patients need treatment during that window to control disease and maintain fitness for infusion — a phase called bridging therapy. Despite how commonly it is used, practices vary widely and little standardized guidance exists. This multinational survey collected responses from 48 centers across 11 countries, primarily Germany (33%) and Italy (21%), to characterize current bridging practices and identify areas of uncertainty.
Most centers infuse 10 to 30 myeloma patients per year with CAR-T. Product access was uneven: 60% of centers had cilta-cel available, 38% ide-cel, and 16% had no access to either outside clinical trials. In Germany, only cilta-cel is currently reimbursed, which shapes prescribing patterns.
Bridging was nearly universal — most centers bridge more than 85% of their patients. 40% of centers described their bridging protocols as not standardized at all, and only 4% as highly standardized. 65% were not enrolled in any bridging-focused trial or registry.
Proteasome inhibitors were the most commonly used bridging agents (90% of centers), followed by immunomodulatory drugs (85%), chemotherapy-based regimens (75%), bispecific antibodies (75%), monoclonal antibodies (69%), and radiotherapy (63%). Among centers with bispecific antibody experience, all agreed bispecifics should be standard for most patients given their superior disease control. Most programs begin bridging within one week of apheresis and continue for one to two months.
Despite progression on bridging, more than 95% of centers still proceed to CAR-T infusion. Regimen selection was driven primarily by prior treatment history and refractoriness (92%), disease burden (77%), and extramedullary disease (69%). Cytogenetic risk and bone marrow involvement factored into decisions far less frequently.
Monitoring during bridging relied on free light chains (96%), serum M-protein (94%), and imaging (75%). Decisions to continue or stop bridging were most often triggered by achieving targeted reductions in serum markers (75%) or signs of rapid progression (73%).
Two recurring concerns shaped bispecific antibody use for bridging. First, when BCMA-directed CAR-T is planned, centers preferred non-BCMA bispecific targets — primarily GPRC5D — to avoid potential antigen modulation or receptor occupancy that might reduce CAR-T efficacy. Second, wash-out intervals before CAR-T infusion were short and variable: BCMA-targeting agents were most commonly stopped two weeks before infusion, GPRC5D-targeting agents also typically two to three weeks before, though practices ranged widely.
Bendamustine was nearly universally avoided before T cell collection (89% of centers), reflecting consensus that it depletes lymphocytes and compromises CAR-T product quality. Once a partial response to bridging was achieved, 60% of centers proceeded directly to infusion rather than delaying for deeper disease reduction.
The responses consistently identified the same unresolved questions: optimal wash-out intervals, particularly for talquetamab; whether bridging affects CAR-T manufacturing quality and in vivo expansion; and clearer indications for radiotherapy as bridging. Centers repeatedly called for comparative prospective data and registry infrastructure to replace the current pattern of highly individualized, experience-based decisions.