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 February 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 February 2026)

"Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens"

Source

Yuqi Wang, Li Zhang, Dong He, Huan Chen, Hanzhen Zhang, Youhai Yuan, Cuilian Zhang, Ru Feng, Yongqiang Wei, Xiaolei Wei; Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens. Blood Neoplasia 2026; 3 (1): 100189. doi: https://doi.org/10.1016/j.bneo.2025.100189  February 1, 2026. 

Overview

The incorporation of CD38-targeted monoclonal antibodies into induction therapy has improved outcome in patients with newly diagnosed multiple myeloma (NDMM), yet the benefit across risk subgroups remains controversial. We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38–based induction regimens in NDMM. Primary outcomes were minimal residual disease (MRD)-negativity and progression-free survival (PFS). Eleven trials encompassing 5588 patients, including 915 with high-risk multiple myeloma (HRMM), were included. Anti-CD38–containing regimens significantly increased MRD-negativity in both transplant-eligible (TE; pooled odds ratio [OR], 2.32; 95% confidence interval [CI], 1.74-3.11) and transplant-ineligible (TIE; pooled OR, 3.26; 95% CI, 2.20-4.84) patients. Among TE patients, MRD-negativity improved in both HRMM (pooled OR, 2.01; 95% CI, 1.41-2.88) and standard-risk MM (pooled OR, 2.74; 95% CI, 1.99-3.84). Anti-CD38 therapy also significantly prolonged PFS in TE (pooled hazard ratio [HR], 0.52; 95% CI, 0.38-0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49-0.61), with an overall survival benefit observed in TIE patients. PFS improvement was consistent across cytogenetic risk and clinical subgroups. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38–based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity.

"Mezigdomide combined with bortezomib disrupts the cell cycle and elicits superior antitumor effects in multiple myeloma"

Source

Chad C. Bjorklund, Marta Larrayoz, Jian Kang, Hsiling Chiu, Natasha Shtraizent, Lei Wu, Shirong Li, Chih-Chao Hsu, Junfei Zhao, Michael Amatangelo, Tracy T. Chow, Krista Wollerman, Ram Kumar Singh, Sneha Sridhara, Shailesh Dudhgaonkar, Prakash Subramanyam, Kaushik Ghosh, Paul G. Richardson, Nizar J. Bahlis, Anjan Thakurta, Jose A. Martinez-Climent, Anita K. Gandhi, Patrick R. Hagner; Mezigdomide combined with bortezomib disrupts the cell cycle and elicits superior antitumor effects in multiple myeloma. Blood Neoplasia 2026; 3 (1): 100179. doi: https://doi.org/10.1016/j.bneo.2025.100179  February 1, 2026. 

Overview

Triplet treatment regimens that combine an immunomodulatory drug, a proteasome inhibitor, and dexamethasone are commonly used for people with newly diagnosed or relapsed and refractory multiple myeloma. Mezigdomide is a newer type of immunomodulatory drug that is being studied in combination with bortezomib and low-dose dexamethasone for patients whose myeloma has already been treated. On its own, mezigdomide works by breaking down key proteins in myeloma cells, called Ikaros and Aiolos, which helps stop cancer cell growth and also supports the immune system in fighting the disease.

In laboratory and animal studies, researchers compared the three-drug combination of mezigdomide, bortezomib, and dexamethasone with each drug alone and with a similar combination that uses pomalidomide instead of mezigdomide. The results showed that the mezigdomide-based triplet was more powerful at slowing myeloma cell growth and causing cancer cells to die. The combination also worked better and faster at breaking down target proteins, even when bortezomib was present. Overall, these findings suggest that this new three-drug combination may provide stronger anti-myeloma effects than current similar regimens, although further clinical studies are needed to confirm its benefit in patients.

"Outcomes of en bloc surgery versus separation surgery for spinal solitary bone plasmacytomas: a multicenter cohort study with long-term follow-up durations"

Source

Minglei Yang, Xiao Liu, Nanzhe Zhong, Xinru Du, Zhaoming Ye, Juan Du, Weiwei Zou, Yangyang Zhou, Qi Jia, Fei Dong, Yan Liu, Hongqing Zhuang, Xinghai Yang, Jian Jiao, Feng Wei, Jianru Xiao, Outcomes of en bloc surgery versus separation surgery for spinal solitary bone plasmacytomas: a multicenter cohort study with long-term follow-up durations, The Spine Journal, 2026, ISSN 1529-9430, https://doi.org/10.1016/j.spinee.2026.01.020. February 1, 2026.  

Overview

Spinal solitary bone plasmacytoma is a rare tumor that can press on the spinal cord or nerves and may require surgery. This study looked at 130 patients treated between 2000 and 2021 and compared two surgical approaches: en bloc surgery, which removes the tumor in one piece, and separation surgery followed by radiation therapy. After surgery, patients in both groups had less pain, better nerve function, and improved overall performance within three months. However, fluid around the lungs occurred more often in patients who had en bloc surgery.

Over the long term, survival rates were similar between the two groups. About 83 percent of patients were alive at five years, and about 67 percent were alive at ten years, with no meaningful difference between the surgical approaches. The length of time before the disease progressed to multiple myeloma was also similar. Local tumor recurrence was uncommon in both groups. However, in patients whose disease had not spread to the bone marrow, en bloc surgery may have offered better long-term disease control. Overall, both treatment strategies provided comparable survival outcomes, and the choice of surgery may depend on individual patient factors, including whether the bone marrow is involved.

"Causal Effects of Hydrophilic Bile Acids on Carfilzomib-Related Cardiovascular Events in Multiple Myeloma: A Mendelian Randomization Study"

Source

Shabnaz, S., Farber-Eger, E., Tantawy, M., Shahisavandi, N., Garrett, T.J., Rubinstein, S.M., Fradley, M.G., Alomar, M.E., DeAvila, D., Shain, K.H., Cornell, R.F., Lenihan, D., Lu, Q., Wells, Q.S., Baz, R.C. and Gong, Y. (2026), Causal Effects of Hydrophilic Bile Acids on Carfilzomib-Related Cardiovascular Events in Multiple Myeloma: A Mendelian Randomization Study. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.70222  February 1, 2026.  

Overview

Carfilzomib is an effective treatment for multiple myeloma, but it can sometimes cause heart-related side effects that affect patient outcomes. In earlier research, scientists found that certain bile acids in the blood might be linked to the risk of heart problems during treatment. In this study, they confirmed in a separate group of patients that higher levels of a bile acid called glycoursodeoxycholic acid were linked to a lower risk of carfilzomib-related heart damage, even after accounting for other heart risk factors such as high blood pressure.

The researchers also used a genetic method called Mendelian randomization to explore whether this bile acid may play a direct protective role. Their findings suggest that higher levels of glycoursodeoxycholic acid may actually help reduce the risk of heart side effects. The study also identified possible biological pathways related to heart function that may be involved. These results suggest that this bile acid could one day help doctors better predict which patients are at higher risk for heart problems during carfilzomib treatment, although larger studies are still needed.

"Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response"

Source

Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Emilia Gigliotta, Marta Di Simone, Paola Pacelli, Francesca Cioffi, Elena Bestoso, Donatella Raspadori, Alessandro Gozzetti, Antonio Solimando, Paula Tabares, Andreas Beilhack, Maria Speciale, Giusy Corsale, Miriam Sciortino, Cristina Aquilina, Fulvio Brucato, Michele Cea, Renato Zambello, Francesca Garofano, Marta Biondo, Francesca Buffa, Nadia Caccamo, Francesco Dieli, Serena Meraviglia, Sergio Siragusa, Cirino Botta; Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response. Blood Neoplasia 2026; 3 (1): 100174. doi: https://doi.org/10.1016/j.bneo.2025.100174  February 1, 2026  

Overview

Multiple myeloma develops through complex interactions between cancerous plasma cells and the bone marrow environment. In this study, researchers analyzed bone marrow samples from 159 patients at different stages of disease, from early, premalignant conditions to active multiple myeloma. Using a specialized data analysis tool, they found that as the disease progressed, the balance of immune cells in the bone marrow changed. In particular, certain ratios between granulocytes and lymphocytes, including T cells, became lower, while T-cell levels increased overall.

Patients who had higher levels of granulocytes compared to lymphocytes or T cells at the start of the study tended to live longer without their disease worsening. Among those treated with daratumumab-based therapy, outcomes were especially better in patients with a higher granulocyte-to–T-cell ratio. The researchers also found that a patient’s own bone marrow granulocytes could help daratumumab kill myeloma cells more effectively. These findings show that the immune makeup of the bone marrow plays an important role in how multiple myeloma progresses and how well patients respond to treatment, and it may help guide future treatment decisions.

"Peripheral Lymphocyte Dynamics in the Immune Microenvironment of Multiple Myeloma During Autologous Stem Cell Transplantation"

Source

Villegas-Valverde C, Casado-Hernandez I, Sotomayor-Lugo F, et al. (February 02, 2026) Peripheral Lymphocyte Dynamics in the Immune Microenvironment of Multiple Myeloma During Autologous Stem Cell Transplantation. Cureus 18(2): e102862. doi:10.7759/cureus.102862     

Overview

Autologous stem cell transplantation remains a standard treatment for multiple myeloma, but it does not cure the disease. As new immune-based treatments are developed, doctors are looking for better ways to measure a patient’s immune system so they can tailor care after transplant. In this study, researchers followed 28 patients undergoing stem cell transplant and measured their blood immune cells before transplant, during stem cell collection, and 21 days after transplant.

They found that most patients had very low B-cell levels at the start. By day 21 after transplant, levels of helper T cells, B cells, and the CD4/CD8 ratio had dropped significantly compared with baseline. Although the total number of lymphocytes infused during transplant was lower than published target levels, the main immune cell groups met recommended thresholds, which may suggest a favorable outlook. Overall, this study provides early reference points for how immune cells change around the time of transplant and suggests that monitoring these cells could help guide future treatment decisions.

"Hypermethylation-mediated silencing of RASD1 drives multiple myeloma pathogenesis"

Source

Yi, C., Cai, Y., Ren, N. et al. Hypermethylation-mediated silencing of RASD1 drives multiple myeloma pathogenesis. Blood Res. (2026). https://doi.org/10.1007/s44313-026-00125-6 February 2, 2026.     

Overview

This study looked at a gene called RASD1 and its role in multiple myeloma. Researchers analyzed bone marrow samples from 26 people newly diagnosed with multiple myeloma and compared them with samples from healthy individuals. They found that RASD1 levels were much lower in patients with myeloma. Lower levels of this gene were linked to more advanced disease, anemia, high calcium levels, and higher amounts of M-protein in the blood. The researchers also found that measuring RASD1 levels could help distinguish people with myeloma from healthy individuals.

The study showed that RASD1 is often turned off in myeloma cells because of a chemical change to the DNA called hypermethylation. In laboratory experiments, treating myeloma cells with a drug called decitabine reversed this change, restored RASD1 activity, and increased cancer cell death. These findings suggest that RASD1 may normally act as a tumor suppressor, helping to control cell growth, and that its loss may contribute to the development and progression of multiple myeloma

"Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2–4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison"

Source

Lopez-Muñoz, N., Bar, N., Diels, J. et al. Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2–4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison. Adv Ther (2026). https://doi.org/10.1007/s12325-025-03479-y  February 2, 2026.     

Overview

This study compared two CAR T-cell therapies, ciltacabtagene autoleucel and idecabtagene vicleucel, in people with relapsed or refractory multiple myeloma who had already received several prior treatments. Because the drugs were studied in different clinical trials, researchers used a statistical method to adjust the data and make the groups as similar as possible. They then compared outcomes such as how long patients lived without their disease worsening, overall survival, and how well patients responded to treatment.

After adjusting for key differences, patients treated with ciltacabtagene autoleucel had a lower risk of disease progression and a lower risk of death compared with those treated with idecabtagene vicleucel. Patients receiving ciltacabtagene autoleucel were also more likely to have a strong response, including deeper responses where little or no disease could be detected. These updated results, which include longer follow-up, suggest that ciltacabtagene autoleucel may provide greater benefit for patients whose myeloma has been exposed to three major drug classes and has returned after two to four prior lines of therapy.

"An oBservational retrospective Analysis of treatment patternS and Effectiveness of standard of CAre for Multiple Myeloma patients exposed to lenalidomide and a Proteasome inhibitor: BasecaMMp study"

Source

K. Martin Kortüm, James Farrell, Olivia Ashman, Guido Nador, Paul Cislo, Jaime Luna, Moritz Lehne, Keltie O’Neill, Markus Rückert, Kai Strobel, Sebastian Theurich, An oBservational retrospective Analysis of treatment patternS and Effectiveness of standard of CAre for Multiple Myeloma patients exposed to lenalidomide and a Proteasome inhibitor: BasecaMMp study, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.01.013. February 3, 2026.    

Overview

This real-world study looked at treatment patterns and outcomes for 1,834 people in Germany with relapsed or refractory multiple myeloma who had already received lenalidomide and a proteasome inhibitor. The average age was 72, and most patients had received two prior lines of therapy. Nearly one-third of patients were resistant to both drug types, and almost half were resistant to lenalidomide. After their disease returned, patients received a wide range of different treatments, showing there was no clear standard approach.

Overall, patients lived a median of about 13 months without their disease worsening and about 37 months from the start of their next treatment. Outcomes were slightly worse for patients whose disease was resistant to lenalidomide. These results show that many patients in this setting continue to have limited treatment options and modest outcomes, highlighting the need for more effective therapies and clearer treatment strategies.

"Prognostic Factors for High Intraoperative Blood Loss for Multiple Myeloma-Related Bone Disease in the Spine"

Source

Te Velde JP, Zijlstra H, de Reus D, Pierik RJB, Xi AS, Shankar GM, van Royen BJ, Kempen DHR, Schwab JH, Tobert DG. Prognostic Factors for High Intraoperative Blood Loss for Multiple Myeloma-Related Bone Disease in the Spine. Global Spine J. 2026 Feb 3:21925682261422708. doi: 10.1177/21925682261422708. Epub ahead of print.  

Overview

Spine surgery for people with multiple myeloma can lead to significant blood loss during the operation. In this study, researchers reviewed records from 158 adults who had spine surgery over a 20-year period to identify factors linked to higher blood loss. On average, patients lost about 750 milliliters of blood during surgery. More extensive procedures, such as removing part of a vertebra and stabilizing the spine, were linked to greater blood loss compared with less complex surgeries. Operations in the lower back were also associated with more bleeding than those in the neck.

Patients with lower platelet counts, which help the blood clot, and those who had longer surgeries were more likely to experience higher blood loss. In addition, a patient’s overall health and physical function, measured by performance status, were linked to the amount of blood lost. These findings may help doctors better assess risk before surgery, plan for possible blood transfusions, and guide shared decision-making with patients.

"Predicting adverse events for risk stratification of chemotherapy based stem cell mobilization in multiple myeloma"

Source

Schwarz, F., Levien, L., Maulhardt, M. et al. Predicting adverse events for risk stratification of chemotherapy based stem cell mobilization in multiple myeloma. npj Digit. Med. (2026). https://doi.org/10.1038/s41746-026-02394-y  February 3, 2026. 

Overview

Autologous stem-cell transplantation is an important treatment for multiple myeloma, and collecting stem cells is usually done in the hospital in Germany. This study looked at 109 patients who underwent stem-cell collection to evaluate safety and explore ways to manage care more efficiently. Almost all patients successfully collected stem cells, but about two-thirds experienced serious side effects that required hospitalization.

The researchers used machine learning to predict which patients might develop side effects and when these events might occur. Their models were able to accurately predict some types of side effects, like kidney issues, and estimate the timing of complications within about a day. These findings suggest that with careful risk assessment, some patients could safely undergo stem-cell collection as outpatients, potentially reducing hospital bed use by a third while maintaining safety. This approach could help clinics manage resources more effectively while keeping patients safe.

"Epigenome-Wide Association Studies of Proteasome Inhibitor-Related Cardiotoxicity in Patients with Multiple Myeloma"

Source

Alshammari, R. A., Rubinstein, S. M., Farber-Eger, E., Shaffer, L. L., Tantawy, M., Alomar, M. E., Wells, Q. S., Lenihan, D., Cornell, R. F., Shain, K. H., Baz, R. C., & Gong, Y. (2026). Epigenome-Wide Association Studies of Proteasome Inhibitor-Related Cardiotoxicity in Patients with Multiple Myeloma. Cancers, 18(3), 505. https://doi.org/10.3390/cancers18030505  February 3, 2026. 

Overview

Carfilzomib and bortezomib are proteasome inhibitors commonly used to treat relapsed or refractory multiple myeloma, but both drugs can cause heart-related side effects. This study looked at DNA methylation, an epigenetic change that can affect gene activity, to see if it might be linked to these cardiovascular events. Researchers analyzed DNA from 79 patients receiving either carfilzomib or bortezomib to identify specific sites and regions in the genome associated with heart complications.

They found several DNA sites and one region linked to heart side effects in patients treated with carfilzomib, while fewer and less significant changes were observed in patients treated with bortezomib. The study also highlighted biological pathways that may play a role, including those related to cell signaling, blood pressure regulation, autophagy, and heart tissue structure. These findings suggest that epigenetic factors may contribute to heart risks from these therapies and point to the need for larger studies to confirm these results and potentially guide safer treatment strategies.

"Proteasome Subunit PSMD1 is a Key Therapeutic Target in Multiple Myeloma"

Source

Ting Du, Teng Fang, Sindhu C Pillai, Arghya Ray, Minxing Wang, Xueping Wan, Kenneth Wen, Yuntong Liu, Jingyu Xu, Md Abu Musa, Xiangdong Liu, Mariateresa Fulciniti, Nikhil C. Munshi, Filip Garbicz, Ruben D. Carrasco, Yao Yao, Zhongkun Zhang, Yan Song, Kenneth C. Anderson; Proteasome Subunit PSMD1 is a Key Therapeutic Target in Multiple Myeloma. Blood 2026; blood.2025029358. doi: https://doi.org/10.1182/blood.2025029358  February 3, 2026. 

Overview

Researchers have identified PSMD1, an important part of the proteasome, as being overactive in multiple myeloma and linked to worse outcomes. When PSMD1 was reduced in cancer cells, it caused a buildup of damaged proteins, led to cell death, and lowered tumor cell survival. The study also found that reducing PSMD1 activated immune-related pathways, suggesting it could help the body’s immune system fight the cancer.

Using a targeted approach with small interfering RNA delivered in lipid nanoparticles, the researchers were able to reduce tumor growth in both lab-grown myeloma cells and samples from patients while leaving normal cells unharmed. This approach also overcame resistance to standard proteasome inhibitors and the protective environment of the bone marrow. In mouse models, PSMD1-targeted therapy slowed tumor growth and extended survival. Similar effects were seen in other types of cancer cells, highlighting PSMD1 as a promising target for therapy that could improve treatment outcomes, overcome drug resistance, and potentially enhance immune responses in multiple cancers.

"Burixafor, a CXCR4 inhibitor with a differentiated kinetics profile: results of a phase 2 study for rapid cell mobilization in multiple myeloma and lymphoma patients undergoing transplant"

Source

Sukhtankar, D.D., Cardarelli, P.M., Jalilizeinali, B. et al. Burixafor, a CXCR4 inhibitor with a differentiated kinetics profile: results of a phase 2 study for rapid cell mobilization in multiple myeloma and lymphoma patients undergoing transplant. Ann Hematol 105, 86 (2026). https://doi.org/10.1007/s00277-026-06858-9 February 4, 2026. 

Overview

Burixafor is a drug that blocks the CXCR4 receptor and helps release hematopoietic stem and progenitor cells (HPCs) into the blood for collection, a key step for stem-cell transplants or gene therapies. In this small phase 2 study, 12 patients with multiple myeloma, non-Hodgkin’s lymphoma, or Hodgkin disease received burixafor along with G-CSF, a growth factor that stimulates stem cells. Eleven of the 12 patients successfully collected the target number of stem cells within two sessions, and half achieved this goal in a single session. Blood counts recovered quickly, with neutrophils and platelets returning to normal in about 12 and 22 days, respectively.

The treatment was generally safe, with only two mild side effects linked to the drugs—a case of bone pain and mild diarrhea. Notably, stem-cell mobilization peaked within an hour after burixafor, faster than currently approved CXCR4 inhibitors, which could allow same-day collection and reduce hospital visits. These results support further development of burixafor as a fast, effective, and well-tolerated option for stem-cell mobilization in patients with blood cancers and for gene therapy applications.

"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 2026; https://doi.org/10.1158/2643-3230.BCD-25-0107  February 4, 2026.  

Overview

Treatment for multiple myeloma has rapidly shifted to include immune-based therapies, but achieving long-lasting disease control, especially for high-risk patients, remains challenging. This review examines how current and emerging treatments affect the immune system, what drives resistance to therapy, and how combining or sequencing treatments may improve outcomes. It also summarizes ongoing clinical trials aimed at achieving more durable immune control and highlights strategies to fully eliminate residual disease while stimulating natural or engineered tumor-specific immunity.

By integrating these biological and clinical insights, researchers hope to move beyond simply controlling myeloma to achieving deep, long-lasting immune eradication. Optimizing the use of both natural and synthetic immune responses could allow treatments to be personalized based on a patient’s immune profile, paving the way for more effective, tailored approaches that strengthen long-term survival.

"Tumour-intrinsic features shape T cell differentiation through precursor to symptomatic multiple myeloma"

Source

Foster, K.A., Rees, E., Ainley, L. et al. Tumour-intrinsic features shape T cell differentiation through precursor to symptomatic multiple myeloma. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68718-4  February 5, 2026.  

Overview

Extramedullary multiple myeloma (EMM) is a high-risk form of multiple myeloma that often resists treatment, including modern immunotherapies, and is linked to shorter survival. This study examined the immune environment of EMM tumors using advanced techniques like single-cell RNA sequencing, flow cytometry, and spatial transcriptomics. Researchers found that T cells and natural killer (NK) cells were the most common immune cells in these tumors, but the balance of immune cells was different from that in the bone marrow. EMM tumors had fewer CD4+ T cells, more regulatory CD16− NK cells, and a lower ratio of effector immune cells to tumor cells. About half of the tumors contained many exhausted, tumor-reactive CD8+ T cells, and immune checkpoints such as PD-1 and NKG2A were highly expressed.

These findings show that the immune environment in EMM is less effective at killing tumor cells and that direct interactions between immune cells and tumor cells may contribute to T-cell exhaustion. Understanding these differences could help guide new strategies to improve immune responses in this high-risk form of myeloma.

"Single-Cell Multiomics Reveals Regulatory Mechanisms of CAR T Cell Persistence and Dysfunction in Multiple Myeloma"

Source

Lorea Jordana-Urriza, Guillermo Serrano, Sergio Camara-Peña, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Aintzane Zabaleta, Aina Oliver-Caldes, Marta Español-Rego, Diego Alignani, Teresa Lozano, Saray Rodriguez-Diaz, Elena Iglesias, Valentin Cabañas, Juan L. Reguera, Veronica Gonzalez-Calle, Maria V. Mateos, Fermin Sanchez-Guijo, Bruno Paiva, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Azucena Gonzalez-Navarro, Manel Juan, Carlos Fernandez de Larrea, Esteban Tamariz, Ana Alfonso-Pierola, Paula Rodriguez-Otero, Jesus San-Miguel, Mikel Hernaez, Juan R. Rodriguez-Madoz, Felipe Prosper; Single-Cell Multiomics Reveals Regulatory Mechanisms of CAR T Cell Persistence and Dysfunction in Multiple Myeloma. Blood Neoplasia 2026; 100203. doi: https://doi.org/10.1016/j.bneo.2026.100203  February 5, 2026. 

Overview

Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for multiple myeloma, but understanding why these cells sometimes fail to persist or function effectively is still a major challenge. In this study, researchers used advanced single-cell analyses to track BCMA-targeted CAR T cells in bone marrow and blood samples from patients over time. They found that CAR T cells in the bone marrow were more activated but also more exhausted than those in the blood, with key gene regulators driving these changes. Problems in the transition from effector to memory CAR T cells led to more terminally differentiated cells, which correlated with poor persistence and reduced long-term effectiveness.

The study also identified a highly expanded CAR T-cell clone in one patient’s bone marrow that produced high levels of IL-10, a molecule that can dampen immune activity. Activation of the patient’s own T cells further increased IL-10 production, potentially limiting CAR T-cell growth and survival. These findings reveal the regulatory mechanisms that affect CAR T-cell persistence and point to potential molecular targets to improve the durability and effectiveness of CAR T-cell therapy in multiple myeloma.

"Safety of cyclophosphamide infusion time modification from 60 to 30 minutes in selected chemotherapy regimens for lymphoma and multiple myeloma"

Source

Dean S, Beall C, Rattu MA. Safety of cyclophosphamide infusion time modification from 60 to 30 minutes in selected chemotherapy regimens for lymphoma and multiple myeloma. J Oncol Pharm Pract. 2026 Feb 5:10781552251411446. doi: 10.1177/10781552251411446. Epub ahead of print.  

Overview

Shortening the infusion time of chemotherapy drugs like cyclophosphamide can improve clinic efficiency, reduce nursing workload, and increase patient satisfaction. While cyclophosphamide is typically recommended to be given slowly, the exact infusion duration is not clearly defined, and practices vary across different treatment regimens. This study reviewed medical records from adult patients who received cyclophosphamide for lymphoma or multiple myeloma at Mount Sinai Health System, comparing 60-minute and 30-minute infusion times.

Among 400 doses analyzed, slightly more adverse events were reported with the 60-minute infusion compared with the 30-minute infusion, but the difference was small and not statistically significant. No severe adverse events (Grade 3 or higher) were linked to the infusion in either group. These results suggest that shortening cyclophosphamide infusions to 30 minutes is a safe option for selected chemotherapy regimens, supporting more efficient and patient-friendly treatment practices.

"TrkA abundance is increased in cutaneous nerves in bortezomib-induced neuropathy"

Source

Jin Y, Cebulla N, Schirmer D, Runau E, Flamm L, Terhorst C, et al. TrkA abundance is increased in cutaneous nerves in bortezomib-induced neuropathy. Brain Pathology. 2026. e70079. https://doi.org/10.1111/bpa.70079  February 5, 2026.   

Overview

Bortezomib, a common treatment for multiple myeloma, can cause peripheral neuropathy, leading to sensory changes and sometimes pain. This study examined skin samples from multiple myeloma patients who developed bortezomib-induced peripheral neuropathy (BIPN) to understand the role of the nerve receptor TrkA and local blood vessels. Researchers found that patients with BIPN had fewer small nerve fibers in the skin but higher levels of TrkA protein in the remaining nerves, which increased with the number of bortezomib treatment cycles.

While TrkA gene expression did not differ between groups, all BIPN patients showed increased blood vessel growth in the skin. Interestingly, patients without pain had more interactions between nerves and blood vessels than those with pain. These findings suggest that changes in TrkA signaling and altered interactions between nerves and blood vessels contribute to the small nerve fiber damage seen in BIPN, offering insight into mechanisms behind bortezomib-related neuropathy and potential targets for intervention.

"Synergistic targeting of the ARID2–MYC axis by pomalidomide and panobinostat overcomes intrinsic IMiD resistance in multiple myeloma"

Source

Yamamoto, J., Asatsuma-Okumura, T., Ito, T. et al. Synergistic targeting of the ARID2–MYC axis by pomalidomide and panobinostat overcomes intrinsic IMiD resistance in multiple myeloma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37740-3 February 5, 2026.  

Overview

Multiple myeloma remains difficult to treat despite advances with proteasome inhibitors, immunomodulatory drugs (IMiDs), and monoclonal antibodies. This study examined a new combination approach using IMiDs together with histone deacetylase inhibitors in relapsed or resistant myeloma. Researchers found that the two drugs work together to suppress the MYC oncogene, producing a stronger anti-cancer effect than either drug alone.

Importantly, this combination was effective even in myeloma cells that are naturally resistant to IMiDs. In these resistant cells, the usual signaling pathway involving IKZF1/3 and IRF4/MYC is disrupted, but the drugs engage an alternative pathway involving ARID2, leading to continued MYC suppression and cancer cell death. These findings reveal a new vulnerability in resistant myeloma cells and provide a scientific basis for designing combination therapies that target this pathway, offering the potential to overcome drug resistance and improve treatment outcomes.

"Daratumumab-based first-line therapy benefit multiple myeloma patients in a real-world setting: a multi-center retrospective propensity score-match study"

Source

Wang, Y., Chen, X., Liang, Q. et al. Daratumumab-based first-line therapy benefit multiple myeloma patients in a real-world setting: a multi-center retrospective propensity score-match study. Ann Hematol 105, 87 (2026). https://doi.org/10.1007/s00277-026-06808-5  February 5, 2026.  

Overview

Adding daratumumab to first-line treatment for newly diagnosed multiple myeloma has been shown in clinical trials to deepen responses and prolong survival, but real-world data are important to understand how it works outside trials. In this study of 761 patients in southern China, researchers compared outcomes for patients who received daratumumab with those who did not, matching groups for disease stage, genetic risk factors, and treatment type. Patients receiving daratumumab had higher rates of deep responses and measurable residual disease negativity after induction therapy.

Three-year progression-free survival and overall survival were also better in the daratumumab group, and these benefits remained after adjusting for patient characteristics. The improvement in survival was particularly seen in patients with certain genetic changes, like gain or amplification of 1q21, but not in those with del17p or t(4;14). Overall, these real-world findings support the use of daratumumab in first-line therapy to achieve stronger responses and longer survival, while highlighting that not all patients benefit equally.

"CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density"

Source

Nicolas Camviel, Davide Gambarotto, Violaine Andre, Raphael Stadelmann, Christian Sieben, Raphael Gottardo, Suliana Manley, Caroline Arber, CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density, Molecular Therapy, 2026, ISSN 1525-0016, https://doi.org/10.1016/j.ymthe.2026.02.004. February 6, 2026.  

Overview

B cell maturation antigen (BCMA) is the main target for CAR T-cell therapies in multiple myeloma, but frequent relapses show the need for additional targets. This study explored a dual-target CAR that recognizes both BCMA and TACI, expressed in patient-derived marrow-infiltrating lymphocytes (MILs). While the patients’ own T cells could not recognize or kill their malignant plasma cells, the dual CAR consistently triggered effective killing, even when antigen levels were very low or undetectable by standard flow cytometry.

Using high-resolution microscopy, researchers found that both BCMA and TACI were actually more abundant on cancer cells than flow cytometry suggested. This allowed the team to show that CAR-MILs were highly sensitive to both targets and could kill myeloma cells at very low antigen levels. These findings support further investigation of TACI as a therapeutic target and highlight the value of advanced imaging techniques to better understand antigen thresholds for CAR T-cell activity.

"Real-world outcomes of SLiM-only multiple myeloma: Korean Multicenter Retrospective analysis (KMM2401 study)"

Source

Yi, J.H., Yoon, D.H., Park, S. et al. Real-world outcomes of SLiM-only multiple myeloma: Korean Multicenter Retrospective analysis (KMM2401 study). Ann Hematol 105, 93 (2026). https://doi.org/10.1007/s00277-026-06851-2 February 6, 2026. 

Overview

SLiM biomarkers were added in 2014 as "myeloma-defining events" because they were linked to rapid progression to active multiple myeloma. However, more recent studies suggested patients with these markers might have better outcomes than originally thought. This study analyzed 72 patients in Korea who were diagnosed with multiple myeloma based only on SLiM biomarkers, looking at those who were actively observed versus those who received immediate treatment. Among patients who were observed, the median time to disease progression was over six years, with a lower two-year risk of progression than previously reported. Patients with more than one focal lesion on MRI had an especially lower short-term risk compared to those with high bone marrow plasma cells or very high free light chain ratios.

For patients who received immediate treatment, first-line therapy led to favorable outcomes, with median progression-free survival of nearly five years. Overall, these findings suggest that some patients with SLiM-only multiple myeloma, particularly those with MRI lesions, may safely delay treatment, while early therapy can still provide strong benefits. This study helps refine risk assessment and treatment decisions for patients identified by SLiM biomarkers.

"Pomalidomide, Cyclophosphamide and Dexamethasone (PCd): Outcomes in Patients With Double- or Triple-Refractory Multiple Myeloma"

Source

M. Hidalgo-Soto, L. G. Rodríguez-Lobato, C. Motlló Borrella, et al., “Pomalidomide, Cyclophosphamide and Dexamethasone (PCd): Outcomes in Patients With Double- or Triple-Refractory Multiple Myeloma,” European Journal of Haematology (2026): 1–10, https://doi.org/10.1111/ejh.70126.  February 6, 2026. 

Overview

Treating double- and triple-refractory multiple myeloma remains a major challenge, but the combination of pomalidomide, cyclophosphamide, and dexamethasone (PCd) continues to be an effective option. This multicenter retrospective study evaluated 179 patients in real-world practice, most of whom were triple-refractory and had previously been treated with lenalidomide or anti-CD38 therapies. The overall response rate was nearly 60%, with triple-refractory patients achieving just over 50% response. Median progression-free survival was about 8 months, and median overall survival was just over 16 months, showing meaningful benefit in this heavily pretreated population.

The most common severe side effects were low white blood cells, anemia, and low platelets, but overall the regimen was considered manageable. These results confirm that PCd remains an effective and feasible treatment for patients with multiple myeloma who have limited options, including those resistant to both lenalidomide and anti-CD38 therapy.

"Differential life expectancies and life years lost associated with multiple myeloma in the United States: A simulation modelling study"

Source

Tzeyu L Michaud, Yi-Hsuan Shih, Mengmeng Ji, John Huber, Wei Zhang, Mei Wang, Martin W Schoen, Theodore S Thomas, Graham A Colditz, Jr-Shin Li, Su-Hsin Chang, Differential life expectancies and life years lost associated with multiple myeloma in the United States: A simulation modelling study, The Oncologist, 2026;, oyag030, https://doi.org/10.1093/oncolo/oyag030 February 6, 2026. . 

Overview

Multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS), affect different populations unequally, with non-Hispanic Black individuals and men experiencing higher disease burdens. This study used a simulation model to estimate remaining life years and life years lost for people with MGUS or MM, taking race and gender into account. Results showed that non-Hispanic Black men with MGUS had about 18 years of life remaining compared with 21 years for non-Hispanic White men, and life years lost due to MM were highest in non-Hispanic White women (around 18 years) and lowest in non-Hispanic Black men (around 14 years).

These findings highlight significant racial and gender disparities in the impact of MGUS and MM on lifespan. They suggest that prevention and management strategies should be tailored, such as increasing disease monitoring in non-Hispanic Black populations and improving treatment adherence for men, to reduce these inequities and improve outcomes.

"Immune heterogeneity at diagnosis influences treatment response and survival in multiple myeloma"

Source

Wang, Y., Lan, T., Gu, S. et al. Immune heterogeneity at diagnosis influences treatment response and survival in multiple myeloma. Discov Onc (2026). https://doi.org/10.1007/s12672-026-04603-2 February 6, 2026. 

Overview

This study shows that the immune system at diagnosis can predict outcomes in multiple myeloma (MM). Researchers analyzed 703 newly diagnosed patients, measuring blood immune cells and serum cytokines. They created an immune risk score (IM) based on factors like CD4⁺/CD8⁺ ratio, IL-6, IL-8, sIL-2R, and complement C3, which divided patients into high- and low-risk groups.

Patients in the low-risk group lived significantly longer (median 64.5 months) than those in the high-risk group (median 32.2 months). The immune score was an independent predictor of survival and worked across different treatment types, showing that a patient’s baseline immune profile can improve prognostic assessment and help guide personalized MM care.

"A Comprehensive Analysis of Common Cytogenetic Abnormalities in Multiple Myeloma: From Basic Research to Clinical Applications"

Source

Chenbo Yang, Xiaonan Liu, Yiwei Li, Jingbo Xiao, Chongli Zhang, Na Zhao, Jiao Shu, Gongchang Li, Ting Luo, Kuisheng Chen, Miaomiao Sun, A Comprehensive Analysis of Common Cytogenetic Abnormalities in Multiple Myeloma: From Basic Research to Clinical Applications, Pathology, 2026,ISSN 0031-3025, https://doi.org/10.1016/j.pathol.2025.09.013. February 7, 2026.

Overview

This study shows that specific cytogenetic abnormalities strongly influence prognosis in newly diagnosed multiple myeloma (NDMM). Researchers analyzed 52 patients for six key abnormalities, including RB1 deletion, 1q21 gain, P53 deletion, and IGH translocation. They found that most abnormalities were linked to advanced disease, worse blood parameters, aggressive tumor features, and shorter overall survival (OS) and progression-free survival (PFS).

Patients with P53 deletion were at particularly high risk, and those with multiple high-risk abnormalities (“triple hit”) had the poorest outcomes and lower response rates to standard VRd therapy. The findings highlight the importance of assessing multiple cytogenetic markers to refine risk stratification and guide individualized treatment strategies in MM.

"Cardiovascular medications and treatment outcomes in multiple myeloma: insights from phase III clinical trials"

Source

Abuhelwa, A.Y., Almansour, S.A., Al-Shamsi, H.O. et al. Cardiovascular medications and treatment outcomes in multiple myeloma: insights from phase III clinical trials. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37464-4  February 7, 2026. 

Overview

This study examined how cardiovascular medications affect outcomes in multiple myeloma (MM) patients starting daratumumab, lenalidomide, or bortezomib-based therapy. Researchers analyzed 1,804 patients from three Phase III trials, focusing on drugs like ACE inhibitors/ARBs, beta-blockers, calcium channel blockers, diuretics, and statins. They found that ACE inhibitors/ARBs were linked to better progression-free survival but also higher rates of severe adverse events, while diuretics were similarly associated with severe adverse events.

Other cardiovascular drugs showed no significant impact on survival or toxicity. These findings suggest that while some medications may offer benefits, they also carry safety risks, highlighting the need for further study to guide their use in MM patients.

"Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma"

Source

K. Tang, D. Jiang, P. Ke, et al. “Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.” Advanced Science (2026): e18975. https://doi.org/10.1002/advs.202518975 February 8, 2026. 

Overview

This study identifies PRKCN as a key driver of multiple myeloma (MM) progression and drug resistance. PRKCN is regulated by NF-κB signaling and forms a feed-forward loop with IRF4, while also activating the mTORC1/C2–IRF4 axis to promote MM cell growth.

Knocking down PRKCN reduces tumor growth, overcomes drug resistance, and increases sensitivity to interferon. Treatment with an orally bioavailable PRKCN inhibitor suppressed MM growth in cell lines and patient-derived xenografts, highlighting PRKCN as a promising therapeutic target in MM.

"Cutting-Edge Technologies to Decode Tumor Microenvironment in Multiple Myeloma"

Source

Gramegna, Doriana, Paolo Mondelli, Susanna A. Pappagallo, et al. 2026. “Cutting-Edge Technologies to Decode Tumor Microenvironment in Multiple Myeloma,” Hematological Oncology: e70171. https://doi.org/10.1002/hon.70171.  February 8, 2026. 

Overview

This review highlights how the tumor microenvironment (TME) drives multiple myeloma (MM) progression and therapy resistance. Advances in single-cell omics, spatial transcriptomics, mass cytometry, and imaging now allow detailed mapping of tumor–immune interactions and reveal spatial heterogeneity that affects outcomes. Integrating these approaches with computational tools and machine learning can identify prognostic biomarkers and support personalized, immune-informed treatment strategies, although technical complexity and standardization remain challenges for clinical implementation.

"Identification of Extracellular Vesicle Signatures of Daratumumab Treated Multiple Myeloma"

Source

Brennan, K., K. F. Iversen, A. Blanco-Fernández, T. Lund, T. Plesner, and M. M. Mc Gee. 2026. “Identification of Extracellular Vesicle Signatures of Daratumumab Treated Multiple Myeloma.” Journal of Extracellular Vesicles 15, no. 2: e70213. https://doi.org/10.1002/jev2.70213  February 8, 2026. . 

Overview

This study identified protein signatures in peripheral blood extracellular vesicles (EVs) from multiple myeloma (MM) patients treated with daratumumab (DARA). Compared with healthy controls, MM EVs showed higher levels of CD31, CD36, and CD44 and lower CD8 and LAT1, while EVs from long-term responders had elevated CD38, LAT1, and PDL1. Two EV-based signatures were defined—one diagnostic and one predictive—which could serve as non-invasive liquid biopsies to monitor MM patient response to DARA.

"PET imaging of XPO1 engagement with [18F]selinexor: A pharmacodynamic theranostic strategy for multiple myeloma"

Source

Xinlin Zhong, Lizhen Wang, Junjie Yan, Chen Su, Xinyu Wang, Donghui Pan, Yuping Xu, Chongyang Chen, Min Yang, PET imaging of XPO1 engagement with [18F]selinexor: A pharmacodynamic theranostic strategy for multiple myeloma, Bioorganic Chemistry, 2026, 109625, ISSN 0045-2068, https://doi.org/10.1016/j.bioorg.2026.109625. February 8, 2026. 

Overview

This study developed [¹⁸F]selinexor, a PET radiotracer derived from selinexor, to noninvasively image XPO1 in multiple myeloma (MM). In preclinical models, the tracer showed XPO1-specific binding, favorable pharmacokinetics, and tumor retention, with uptake peaking 3 hours post-injection. Repeated selinexor treatment reduced tumor uptake independently of tumor size, correlating with decreased XPO1 expression, demonstrating the tracer’s potential to monitor in vivo target engagement and pharmacodynamic effects during therapy.

"PET imaging of XPO1 engagement with [18F]selinexor: A pharmacodynamic theranostic strategy for multiple myeloma"

Source

Xinlin Zhong, Lizhen Wang, Junjie Yan, Chen Su, Xinyu Wang, Donghui Pan, Yuping Xu, Chongyang Chen, Min Yang, PET imaging of XPO1 engagement with [18F]selinexor: A pharmacodynamic theranostic strategy for multiple myeloma, Bioorganic Chemistry, 2026, 109625, ISSN 0045-2068, https://doi.org/10.1016/j.bioorg.2026.109625. February 8, 2026. 

Overview

This study developed [¹⁸F]selinexor, a PET radiotracer derived from selinexor, to noninvasively image XPO1 in multiple myeloma (MM). In preclinical models, the tracer showed XPO1-specific binding, favorable pharmacokinetics, and tumor retention, with uptake peaking 3 hours post-injection. Repeated selinexor treatment reduced tumor uptake independently of tumor size, correlating with decreased XPO1 expression, demonstrating the tracer’s potential to monitor in vivo target engagement and pharmacodynamic effects during therapy.

"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 2026; https://doi.org/10.1158/2643-3230.BCD-25-0384  February 9, 2026. 

Overview

This review summarizes advances in first-line multiple myeloma treatment, including quadruplet regimens with proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and autologous stem cell transplantation, which have improved survival. It highlights risk-adapted strategies, measurable residual disease–guided approaches, and the emerging integration of CAR T cells and bispecific antibodies into upfront therapy. The authors emphasize that individualized, biology-driven treatment may enable durable, treatment-free remissions in select patients.

"Model Development and Internal Validation of a Machine Learning Risk Score for High Free Light Chain Myeloma"

Singh, S., Roshan, R., Jain, K. et al. Model Development and Internal Validation of a Machine Learning Risk Score for High Free Light Chain Myeloma. Indian J Hematol Blood Transfus (2026). https://doi.org/10.1007/s12288-026-02340-8  February 9, 2026.  

Overview

This study developed and internally validated a machine learning–based risk score to predict early mortality in high free light chain (iFLC) multiple myeloma, a group at high risk of renal impairment and poor outcomes. Using XGBoost and SHAP analysis, changes in FLC, age, and creatinine were identified as the strongest predictors, allowing patients to be stratified into high- and low-risk groups with clear differences in overall survival. The findings highlight the value of dynamic biomarkers in risk assessment and demonstrate the potential of explainable AI to identify high-risk subgroups for future clinical application.

"Complementary Roles of Next-Generation Flow and Next-Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma"

Park MS, Lim DJ, Kim HJ, Cho D, Yoon SE, Kim SJ, Kim K, Kim HY. Complementary Roles of Next-Generation Flow and Next-Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma. J Korean Med Sci. 2025 Sep;41(6):e5. https://doi.org/10.3346/jkms.2026.41.e5  February 9, 2026.   

Overview

This study compared next-generation flow (NGF) and next-generation sequencing (NGS) MRD assays in multiple myeloma patients to assess their diagnostic performance and clinical utility. MRD detection rates were 43.6% for NGF and 29.1% for NGS, with moderate concordance between assays. Patients positive for MRD by either method had significantly lower 3-year progression-free survival, highlighting that both NGF and NGS provide complementary information for disease monitoring and prognosis in MM.

"Discovery of p300 Histone Acetyltransferase Inhibitors Bearing an Imidazo[4,5-b]pyridine-2-one Scaffold for the Treatment of Multiple Myeloma"

Ying Xiong, Xiaoxue Tan, Hong Yang, Yujie Wang, Qiongyu Shi, Ying Zhang, Xinsheng Lei, Yingxia Li, Xun Huang, Zonglong Chen, Discovery of p300 Histone Acetyltransferase Inhibitors Bearing an Imidazo[4,5-b]pyridine-2-one Scaffold for the Treatment of Multiple Myeloma, European Journal of Medicinal Chemistry, 2026, 118646, ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2026.118646. February 9, 2026. 

Overview

This study developed novel p300 histone acetyltransferase (HAT) inhibitors for cancer therapy, focusing on multiple myeloma. Among them, compound B6 showed strong in vitro activity, suppressed c-Myc expression, and reduced H3K18ac/H3K27ac levels in MM cells. Oral administration of B6 significantly inhibited tumor growth in mouse xenograft models, highlighting its potential as a potent, orally active lead compound for anticancer drug development.

"Analysis of Outcomes Following Change in Granulocyte Colony-Stimulating Factor Administration Policy in Multiple Myeloma Patients Receiving Melphalan Autologous Bone Marrow Transplant"

Maranda Renouard, Julie Asch, Jacob Wilkes, Daanish Hoda, Prashant Sharma, Riki Ashment, Ryan Jensen, Bradley Hunter, Analysis of Outcomes Following Change in Granulocyte Colony-Stimulating Factor Administration Policy in Multiple Myeloma Patients Receiving Melphalan Autologous Bone Marrow Transplant, Transplantation Reports, 2026, 100199, ISSN 2451-9596, https://doi.org/10.1016/j.tpr.2026.100199. February 9, 2026.  

Overview

This study evaluated the impact of earlier G-CSF administration after autologous stem cell transplant in multiple myeloma patients. Starting G-CSF on Day +1 instead of Day +6 shortened time to neutrophil engraftment by about 1 day and reduced hospital length of stay by 1 day, without increasing engraftment syndrome or affecting 1-year overall survival. Early G-CSF use also reduced antibiotic duration and overall transplant costs, supporting its safety and potential efficiency benefits.

"ESR Essentials: bone marrow MRI in oncology—practice recommendations by the European Society of Musculoskeletal Radiology"

Lecouvet, F.E., Taihi, L., Kirchgesner, T. et al. ESR Essentials: bone marrow MRI in oncology—practice recommendations by the European Society of Musculoskeletal Radiology. Eur Radiol (2026). https://doi.org/10.1007/s00330-025-12307-4 February 9, 2026.  

Overview

This article provides guidance on using MRI to assess bone marrow involvement in cancer, including multiple myeloma. MRI is recommended as the primary imaging tool for detecting skeletal metastases, evaluating treatment response, and monitoring disease recurrence, with whole-body MRI preferred for comprehensive assessment and axial skeleton MRI suitable for targeted follow-up. Standardized protocols using anatomical sequences and diffusion-weighted imaging, along with quantitative biomarkers like ADC and fat fraction, improve diagnostic accuracy and support optimal patient management.

"The impact of cardiac amyloidosis on patients with multiple myeloma: a systematic review and meta-analysis"

Novo, G., Stabile, F., Di Lisi, D. et al. The impact of cardiac amyloidosis on patients with multiple myeloma: a systematic review and meta-analysis. Cardio-Oncology (2026). https://doi.org/10.1186/s40959-025-00435-1  February 10, 2026.  

Overview

This systematic review and meta-analysis evaluated the impact of cardiac AL amyloidosis on survival in multiple myeloma patients. Across five studies including 272 patients, those with cardiac involvement had significantly higher mortality, with a nearly fivefold increase at 12 months and consistently elevated risk at 24 and 36 months. Overall, cardiac AL amyloidosis is a major predictor of poor survival in multiple myeloma, highlighting the need for careful cardiac assessment and risk stratification in affected patients.

"Emerging roles of RNA m⁶: A modification in multiple myeloma pathogenesis and treatment resistance (Review)"

Maimaitiyiming, Y., Hu, S., Bai, D., Guan, Y., Bu, N., Hao, W., & Maimaiti, M. (2026). Emerging roles of RNA m⁶: A modification in multiple myeloma pathogenesis and treatment resistance (Review). International Journal of Oncology, 68, 40. https://doi.org/10.3892/ijo.2026.5853  February 10, 2026.   

Overview

This review examines the role of RNA modifications, specifically N6-methyladenosine (m6A), in multiple myeloma. Dysregulation of m6A machinery contributes to disease progression, heterogeneity, and drug resistance by affecting RNA metabolism, signaling pathways, and interactions with the bone marrow microenvironment. Targeting m6A regulators may offer a new therapeutic strategy to overcome treatment resistance and improve outcomes for patients with multiple myeloma.

"Real-world clinical outcomes of autologous stem cell transplantation in Chinese patients with newly diagnosed multiple myeloma: a systematic literature review"

You J, Zhang Y, Meng Y, Zhao Y, Huang H, Chen W, Meng J. Real-world clinical outcomes of autologous stem cell transplantation in Chinese patients with newly diagnosed multiple myeloma: a systematic literature review. Ther Adv Hematol. 2026 Feb 10;17:20406207261417132. doi: 10.1177/20406207261417132. 

Overview

This systematic review analyzed real-world data on autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma in China. ASCT recipients were younger, had earlier-stage disease, and fewer high-risk cytogenetic features compared to non-ASCT patients. ASCT was associated with higher response rates and better 5-year overall and progression-free survival, and plerixafor-based mobilization improved stem cell collection, though advanced stage, IgD subtype, and poor pre-transplant response reduced its effectiveness.

"Evidence for the Monitoring of Minimal Residual Disease Dynamics to Guide Clinical Practice in Patients with Multiple Myeloma"

Gan, X., Li, L., Zhang, L. et al. Evidence for the Monitoring of Minimal Residual Disease Dynamics to Guide Clinical Practice in Patients with Multiple Myeloma. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01199-z  February 10, 2026. 

Overview

This review highlights the clinical importance of minimal residual disease (MRD) in multiple myeloma. Sustained MRD negativity is linked to significantly better survival, while loss of MRD negativity predicts disease progression. The review discusses how MRD dynamics can guide treatment decisions and the challenges of implementing MRD monitoring in real-world clinical practice.

"FTO-Mediated m6A Demethylation of SERPINF1 Attenuates Multiple Myeloma Progression via the Wnt/β-Catenin Pathway"

Dong X, Chen X, Tian Y, Wang L, Wang W. FTO-Mediated m6A Demethylation of SERPINF1 Attenuates Multiple Myeloma Progression via the Wnt/β-Catenin Pathway. J Microbiol Biotechnol. 2026 Feb 11;36:e2510039. doi: 10.4014/jmb.2510.10039. 

Overview

This study shows that the m6A demethylase FTO promotes multiple myeloma progression by reducing SERPINF1 expression. Overexpression of SERPINF1 suppresses tumor growth and inhibits key Wnt/β-catenin signaling molecules. Mechanistically, FTO-mediated m6A demethylation decreases SERPINF1 via IGF2BP1, and restoring SERPINF1 can reverse FTO-driven oncogenic effects.

"Unheard Voices: Unmet Psychosocial Needs of Carers of Myeloma—A Service Evaluation Exploring Patient and Carer Perceived Benefits of Attending a Myeloma Support Group"

Sweeney, K., Bolger, J. and Niblock, A. (2026), Unheard Voices: Unmet Psychosocial Needs of Carers of Myeloma—A Service Evaluation Exploring Patient and Carer Perceived Benefits of Attending a Myeloma Support Group. eJHaem, 7: e70241. https://doi.org/10.1002/jha2.70241  February 11, 2026. 

Overview

This evaluation shows that myeloma patients and their carers face significant physical, emotional, and informational burdens, with carers often experiencing anxiety levels equal to or higher than patients. Participation in professionally led support groups improved understanding of disease and treatments, emotional well-being, reduced isolation, and confidence in future planning for both patients and carers. These findings emphasize the importance of including carers in interventions to address psychosocial needs and support quality of life alongside medical care.

"On-Resin DIAMSAR-Conjugated CD38-Targeted Peptides and Their Inverso and Dimeric-Inverso Analogs for PET Imaging of Multiple Myeloma"

Sharma AK, Tang R, Zheleznyak A, Manion B, Teubner E, Prior JL, Bauer T, Dyer MR, Lees S, Kelly K, Shokeen M. On-Resin DIAMSAR-Conjugated CD38-Targeted Peptides and Their Inverso and Dimeric-Inverso Analogs for PET Imaging of Multiple Myeloma. Bioconjug Chem. 2026 Feb 11. doi: 10.1021/acs.bioconjchem.5c00577. Epub ahead of print. 

Overview

This study developed and evaluated a novel CD38-targeted peptide PET tracer for multiple myeloma. By converting the peptide to d-amino acids and creating a dimeric form, researchers achieved high serum stability, enhanced binding affinity, and improved tumor uptake in cell and mouse models. The dimeric tracer ([64Cu]Cu-Dimer_D) enabled clear tumor visualization and shows promise as a molecular imaging tool for detecting and monitoring MM.

"Advances in the pathophysiology and treatment of anaemia in multiple myeloma"

Giuliani, Nicolaa,b; dalla Palma, Benedettab; Notarfranchi, Laurac. Advances in the pathophysiology and treatment of anaemia in multiple myeloma. Current Opinion in Hematology ():10.1097/MOH.0000000000000911, February 11, 2026. | DOI: 10.1097/MOH.0000000000000911  

Overview

This review discusses anemia in multiple myeloma, highlighting both disease-related and treatment-related causes. Immunomodulatory drugs, anti-CD38 antibodies, bispecific antibodies, and CAR-T therapies can all contribute to reduced red blood cell production through direct effects on progenitor cells or cytokine-mediated mechanisms. Current management includes transfusions and erythropoietin-stimulating agents, with new therapies like activin receptor fusion proteins under investigation.

"Genomic Proximity Mapping for Identification of Chromosomal Aberrations in Multiple Myeloma"

R. K. Kandasamy, J.-S. Hsu, S. Eacker, et al., “Genomic Proximity Mapping for Identification of Chromosomal Aberrations in Multiple Myeloma,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70219. February 11, 2026.   

Overview

This letter highlights the potential of Genomic Proximity Mapping (GPM) to improve the detection of genetic abnormalities in multiple myeloma (MM). In a cohort of five newly diagnosed patients, GPM confirmed all FISH-identified alterations and revealed additional high-risk genomic events, including complex rearrangements, chromothripsis, copy-neutral loss of heterozygosity, and structural variants that were missed by conventional methods. These findings demonstrate that GPM can provide a more comprehensive genomic profile, which could better inform risk stratification, treatment selection, and personalized therapy decisions in MM.

"EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway"

Li Y, Wilson A, Chrisochoidou Y, Martin S, Bird S, Morales S, Leiro M, Kozik Z, Crump NT, Roumeliotis TI, Choudhary J, Pawlyn C. EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway. Haematologica; https://doi.org/10.3324/haematol.2025.288024 [Early view].  February 12, 2026.   

Overview

This study explores a strategy to overcome resistance to immunomodulatory drugs (IMiDs) and next-generation Cereblon modulators (CELMoDs) in multiple myeloma (MM). Using resistant MM cell lines, the authors show that combining Tazemetostat, an EZH2 inhibitor, with IMiDs/CELMoDs suppresses IRF4 expression, induces apoptosis, and produces synergistic cell death. Mechanistically, EZH2 inhibition reduces IKZF1 binding to the IRF4 promoter, enhancing the effect of IMiDs/CELMoDs, suggesting a promising approach for patients with primary or acquired IMiD resistance.

"A new perspective on aging and multiple myeloma"

Ling Zhong, Kai Dong, Jialing Xiao, Bo Gong, A new perspective on aging and multiple myeloma, Medicine Plus, 2026, 100126, ISSN 2950-3477, https://doi.org/10.1016/j.medp.2026.100126. February 12, 2026.    

Overview

This review explains how aging drives multiple myeloma (MM) development and progression. Aging amplifies DNA damage, genomic instability, and epigenetic drift in plasma cell precursors, while immune senescence and chronic inflammation create a permissive bone marrow environment for malignant cells. Senescent cells and mitochondrial dysfunction further suppress immune surveillance and promote tumor survival, suggesting that interventions targeting immunosenescence, inflammaging, and senescent cell clearance may improve outcomes for older MM patients.

"High-throughput monoclonal gammopathy community monitoring programme"

Agarwal, G., Campbell, L., Carty, O., Larham, J., Knight, E., Moore, S., Gooding, S., Kothari, J., Browning, J., Evans, J., Ferguson, L., Vieira, A., Swanborough, L., Roberts, P., Bateman, E., Sadler, R. and Ramasamy, K. (2026), High-throughput monoclonal gammopathy community monitoring programme. Br J Haematol. https://doi.org/10.1111/bjh.70366 February 12, 2026.     

Overview

This report describes a community-based program, OxCOM, for monitoring incidental monoclonal gammopathy (iMG) using a risk-adapted approach. Patients were stratified into low-, intermediate-, and high-risk groups, with follow-up intensity tailored accordingly—remote monitoring for low-risk, virtual clinics for intermediate-risk, and urgent face-to-face review for high-risk cases. Over two years, OxCOM achieved high follow-up fidelity, timely detection of plasma cell malignancies, and efficient allocation of healthcare resources, demonstrating that risk-stratified, high-throughput monitoring is a safe, effective, and scalable approach for iMG surveillance.

"Fine Mapping of MHC Region Identifies Novel Susceptibility Loci in Multiple Myeloma When Comparing With Its Precursor Monoclonal Gammopathy of Unknown Significance"

S. Arsang-Jang, B. Massat, G. Pareek, et al., “Fine Mapping of MHC Region Identifies Novel Susceptibility Loci in Multiple Myeloma When Comparing With Its Precursor Monoclonal Gammopathy of Unknown Significance,” HLA 107, no. 2 (2026): e70589, https://doi.org/10.1111/tan.70589.  February 13, 2026.    

Overview

This study investigated how specific HLA genes influence the progression from MGUS to multiple myeloma (MM). Comparing 238 MGUS patients with 618 MM patients, the researchers identified several HLA alleles—such as HLA-A30:01, HLA-B08:01, and HLA-DRB1*15:03—associated with increased or decreased MM risk. The findings suggest that changes in HLA class I and II molecules may affect immune recognition of malignant cells, highlighting a genetic component in MM susceptibility and the need for further validation.

"m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1"

Liu, Y., Geng, Y., Zheng, B. et al. m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1. J Transl Med (2026). https://doi.org/10.1186/s12967-026-07799-7  February 13, 2026. 

This study explored the role of the transcription factor ETV1 in multiple myeloma (MM). Researchers found that ETV1 is overexpressed in MM and linked to worse patient outcomes, promoting both MM cell growth and M2-type tumor-associated macrophage (TAM) polarization. Mechanistically, METTL3 increases ETV1 expression through m6A methylation, and ETV1 activates RBMS1 to drive tumor progression, highlighting the ETV1/RBMS1 axis as a potential therapeutic target in MM.

"Global epidemiology and burden of multiple myeloma from 1990 to 2021 with projections to 2045 based on the global burden of disease study"

Xu, H., Chen, X., Wang, W. et al. Global epidemiology and burden of multiple myeloma from 1990 to 2021 with projections to 2045 based on the global burden of disease study 2021. Discov Onc (2026). https://doi.org/10.1007/s12672-026-04616-x  February 13, 2026. 

This study analyzed the global epidemiology and disease burden of multiple myeloma (MM) from 1990 to 2021, with projections to 2045. It found that MM incidence, prevalence, and deaths have increased 2–3-fold, with higher burdens in high-income regions due to aging populations and better diagnostics. High body mass index was identified as a key risk factor, and projections suggest continued growth in case numbers, highlighting the need for equitable healthcare access, prevention strategies, and global policy interventions.

"Y chromosome-linked EIF1AY deletion drives sex differences in multiple myeloma"

Feng, Z., Bai, J., Li, Y. et al. Y chromosome-linked EIF1AY deletion drives sex differences in multiple myeloma. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01317-0 February 14, 2026. 

This study identifies the Y-linked gene EIF1AY as a tumor suppressor contributing to sex differences in multiple myeloma (MM). Partial loss of EIF1AY in male patients is associated with disease progression, poorer treatment response, and shorter survival. Mechanistically, EIF1AY forms a complex with RPS4Y1 to stabilize CD134 mRNA, suppressing IL-4/IL-13 signaling and limiting DDR1-mediated M2 macrophage polarization. Loss of this regulatory axis enhances pro-tumor macrophage activity and MM cell proliferation, revealing a novel immune pathway underlying worse outcomes in males and suggesting EIF1AY as a potential precision immunotherapy target..

"New Approaches for Measurable Residual Disease Assessment in Multiple Myeloma: Integrating NGS, Mass Spectrometry, and Next-Generation Flow Cytometry to Monitor Treatment Response"

Mohan Lal, B., Kumar, S.K. New Approaches for Measurable Residual Disease Assessment in Multiple Myeloma: Integrating NGS, Mass Spectrometry, and Next-Generation Flow Cytometry to Monitor Treatment Response. Curr Hematol Malig Rep 21, 4 (2026). https://doi.org/10.1007/s11899-026-00771-8  February 14, 2026. 

This review highlights measurable residual disease (MRD) as the most powerful prognostic biomarker in multiple myeloma (MM), enabling deeper response assessment, risk stratification, relapse prediction, and treatment guidance. Bone marrow–based next-generation flow cytometry and sequencing remain the current standards, but limitations have driven interest in less invasive peripheral blood approaches. Emerging tools—including mass spectrometry–based assays, circulating tumor DNA analysis, droplet digital PCR, and advanced epigenetic profiling—offer promising avenues for dynamic MRD monitoring, with ongoing clinical trials aiming to define their optimal role in routine MM management.

"Validation of the 2025 IMS/IMWG risk classification in patients with newly diagnosed multiple myeloma treated with quadruplets and autologous stem cell transplant"

Venkatesh P, Ravi G, Dhakal B, Callander NS, Medvedova E, Dholaria BR, et al. Validation of the 2025 IMS/IMWG risk classification in patients with newly diagnosed multiple myeloma treated with quadruplets and autologous stem cell transplant. Br J Haematol. 2026; 00: 1–8. https://doi.org/10.1111/bjh.70359  February 15, 2026. 

This study validated the updated 2025 International Myeloma Society (IMS) and International Myeloma Working Group (IMWG) high-risk criteria in newly diagnosed multiple myeloma (NDMM) patients treated with modern quadruplet therapy plus autologous stem cell transplantation (ASCT). In a cohort of 310 patients, 29% were classified as high-risk under the new criteria and demonstrated significantly inferior progression-free and overall survival compared to standard-risk patients. The revised criteria outperformed legacy cytogenetic-based definitions, more accurately identifying patients at risk of early progression and death despite contemporary therapy, and correcting prior risk misclassification.

"Outcomes of radiation integrated with T-cell–engaging bispecific antibodies in relapsed/refractory multiple myeloma"

Heta Patel, Harper Hubbeling, Kyle Yu, Maribel Carpenter, Michael J. LaRiviere, John P. Plastaras, Adam D. Cohen, Shivani Kapur, Dan T. Vogl, Adam J. Waxman, Edward A. Stadtmauer, Alfred L. Garfall, Sandra Susanibar-Adaniya; Outcomes of radiation integrated with T-cell–engaging bispecific antibodies in relapsed/refractory multiple myeloma. Blood Adv 2026; 10 (4): 1395–1399. doi: https://doi.org/10.1182/bloodadvances.2025017939  February 24, 2026. 

In this single-center retrospective study, investigators evaluated the feasibility and outcomes of radiation therapy (RT) administered concurrently or as salvage in patients with relapsed/refractory multiple myeloma (R/RMM) receiving the bispecific antibodies teclistamab or talquetamab. Among 208 consecutive patients treated with bispecific antibodies, 41 received RT (34 with teclistamab, 12 with talquetamab; 5 during both). Nearly half had high-risk disease per 2025 IMWG criteria, and many had adverse features including elevated ferritin, extramedullary disease (EMD), and extensive prior therapy.

Concurrent RT (CRT; n=29) was delivered early during bispecific therapy, typically within the first two cycles. High local response rates were observed across irradiated sites, particularly for EMD (94%) and skeletal lesions (93%). CRT was feasible, with no RT-attributable cytopenias and manageable rates of cytokine release syndrome and neurotoxicity. However, median progression-free survival (PFS) was short (1.4 months), although a subset achieved durable responses exceeding 12 months.

Salvage RT (SRT; n=23) was administered after initial response for focal progression. Comprehensive SRT (treating all progressing sites) was associated with superior post-RT PFS (2.8 vs 0.9 months) and longer time to next treatment or death (5.4 vs 1.2 months) compared with noncomprehensive SRT. Patients with limited sites of progression and non-EMD targets derived the greatest benefit. No additional immune-related toxicities were observed with SRT.

Overall survival was longer for patients treated with teclistamab than talquetamab, though subgroup sizes were small. Despite the high-risk nature of the cohort, a subset of patients in both CRT and SRT groups achieved PFS beyond 12 months.

These findings suggest that RT can be safely integrated with bispecific antibody therapy and may augment clinical benefit, particularly when used as comprehensive salvage for limited-site progression. Prospective studies are warranted to clarify the immunomodulatory role of RT and define optimal patient selection strategies.

"Bioenergetic diversity and nutrient auxotrophy shape the metabolic landscape of multiple myeloma"

Phyllis S. Y. Chong, Julia Sze Lynn Lim, Tuan Zea Tan, Li Ren Kong, Sanjay de Mel, Aaron Chung Yong Leow, Ernest Gim Seng Yap, Wee Joo Chng; Bioenergetic diversity and nutrient auxotrophy shape the metabolic landscape of multiple myeloma. Blood Adv 2026; 10 (4): 953–959. doi: https://doi.org/10.1182/bloodadvances.2025017676  February 24, 2026. 

This study comprehensively profiled metabolic heterogeneity in multiple myeloma (MM), demonstrating that recurrent cytogenetic subtypes are associated with distinct—but not exclusive—bioenergetic phenotypes, and that metabolic reprogramming contributes to prognosis and drug resistance.

Using Seahorse assays across 12 human myeloma cell lines (HMCLs), investigators identified three bioenergetic clusters. t(4;14) cell lines predominantly exhibited a highly energetic phenotype, whereas t(14;16) displayed intermediate metabolic demands relative to t(11;14). However, substantial heterogeneity existed within translocation groups, indicating that secondary genetic events shape metabolic plasticity. Unlike metabolically quiescent healthy donor B cells, HMCLs demonstrated enhanced glycolytic and/or oxidative phosphorylation (OXPHOS) capacity, with ATP production derived from both pathways rather than conforming strictly to a Warburg phenotype. t(14;16) lines favored OXPHOS reserve capacity, while certain lines (e.g., KMS-18, OPM-2) demonstrated high glycolytic reserve, supported by altered redox states and NADH/NAD ratios.

Quantitative metabolomics profiling (116 central carbon metabolites) further highlighted divergence between normal B cells and MM. Principal component analysis showed tight clustering in healthy controls versus broad dispersion among HMCLs, reflecting metabolic heterogeneity. From differential metabolite mapping, investigators derived a 7-gene metabolic signature (representing 5 metabolites) associated with adverse survival. High expression of this signature correlated with inferior outcomes in both CoMMpass and APEX cohorts, increased progressively from precursor states to relapsed MM, predicted poor response to bortezomib and lenalidomide, and remained independently prognostic beyond ISS staging and certain high-risk cytogenetics. Validation in patient-derived metabolomics and bone marrow plasma proteomics (elevated PGM2, MDH1, FH) reinforced clinical relevance, with higher levels associated with advanced ISS stage.

Functional studies demonstrated subtype-specific nutrient dependencies. High extracellular acidification rate (ECAR) correlated with glucose consumption, while oxygen consumption rate (OCR) was influenced by glutaminolysis. Notably, high glycolysis did not uniformly translate into increased lactate export, suggesting diversion into alternative metabolic pathways or regulatory roles such as lactylation-mediated epigenetic modification. Similarly, ammonia production from glutamine did not strictly correlate with extracellular levels, consistent with metabolic recycling.

Myeloma cells exhibited metabolic rigidity: both glucose and glutamine deprivation impaired viability, yet supraphysiologic supplementation did not enhance survival. Distinct subtypes showed differential growth responses to nutrient availability, highlighting conditional metabolic vulnerabilities.

Importantly, metabolic plasticity contributed to drug resistance. Drug-sensitive lines (e.g., KMS-11) exhibited disrupted ATP production under bortezomib or lenalidomide, whereas resistant lines (e.g., RPMI 8226) maintained ATP output via a glycolytic switch. Isogenic drug-resistant derivatives similarly preserved ATP production under treatment, indicating that sustained bioenergetic capacity under therapeutic stress is a key resistance mechanism.

Overall, this study defines MM as a metabolically heterogeneous disease spanning glycolytic-dominant and mitochondrial-dependent phenotypes. A validated metabolic gene signature provides independent prognostic value, and adaptive ATP preservation emerges as a mechanistic driver of therapy resistance. These findings support integrating metabolic profiling into risk stratification frameworks and targeting metabolic plasticity to overcome treatment resistance.

"Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study"

Sarah Cayla, Lionel Karlin, Jérôme Lambert, Anne Lazareth, Alexis Talbot, Mohamad Mohty, Florent Malard, Marie-Odile Petillon, Salomon Manier, Ibrahim Yakoub-Agha, Denis Caillot, Ingrid Lafon, Xavier Leleu, Niels Moya, Bruno Royer, Jean-Marc Schiano De Colella, Gabriel Brisou, Cyrille Touzeau, Aurore Perrot, Pierre Bories, Laure Vincent, Hanane Guedon, Olivier Decaux, Benoît Ferment, Roch Houot, Steven Le Gouill, Noémie Bigot, Thierry Facon, Jill Corre, Hervé Avet-Loiseau, Philippe Moreau, Bertrand Arnulf; and the Intergroupe Francophone du Myélome , Poor outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study. Blood Adv 2026; 10 (4): 1324–1333. doi: https://doi.org/10.1182/bloodadvances.2025017597  February 24, 2026. 

This national real-world study evaluated outcomes of salvage therapy in 154 patients with relapsed/refractory multiple myeloma who progressed after idecabtagene vicleucel (ide-cel), a BCMA-directed CAR T-cell therapy. Median time to progression following ide-cel was 6.0 months (IQR, 3.0–9.9), underscoring the limited durability of response in this setting.

Post–ide-cel salvage strategies included anti-BCMA bispecific antibodies (BsAbs; n=79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n=12), triplet combinations incorporating an immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n=40), and other regimens (n=23). Overall outcomes were poor, with a median progression-free survival (PFS) of 3.48 months (95% CI, 2.6–6.37) and median overall survival (OS) of 12.12 months (95% CI, 6.6–not reached).

Patients treated with BsAbs achieved a higher overall response rate (ORR ≥PR) compared with non-BsAb regimens (36% vs 13%, P = .002). Notably, non-BCMA–targeted BsAbs demonstrated superior efficacy relative to anti-BCMA BsAbs, with significantly higher ORR (67% vs 30%, P = .018), longer median PFS (9.2 vs 3.81 months, P = .035), and improved median OS (19.48 vs 8.41 months, P = .034). These findings suggest that target switching beyond BCMA may overcome resistance mechanisms emerging after BCMA-directed CAR T-cell therapy.

Adverse prognostic factors included early relapse (≤6 months) following ide-cel (OS 5.95 vs 12.58 months, P = .040), presence of extramedullary disease (OS 6.28 vs 13.8 months, P = .033), and receipt of more than three prior lines of therapy.

In summary, outcomes after ide-cel relapse remain suboptimal. Anti-BCMA BsAbs provide limited benefit, particularly in early relapsers, whereas non-BCMA–targeted bispecific antibodies appear to offer improved clinical efficacy. These data support diversification of antigen targets as a rational post–CAR T therapeutic strategy and highlight the need for optimized sequencing approaches in this high-risk population.

"Enhancing the Safety of Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (MM): Identification of Potentially Modifiable Risk-Factors Associated with Delayed Neurotoxicity and Non-Relapse Mortality"

Sidana, Surbhi et al. Enhancing the Safety of Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (MM): Identification of Potentially Modifiable Risk-Factors Associated with Delayed Neurotoxicity and Non-Relapse Mortality. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 32, Issue 2, S11 – S12 February 2026. 

This national real-world study evaluated outcomes of salvage therapy in 154 patients with relapsed/refractory multiple myeloma who progressed after idecabtagene vicleucel (ide-cel), a BCMA-directed CAR T-cell therapy. Median time to progression following ide-cel was 6.0 months (IQR, 3.0–9.9), underscoring the limited durability of response in this setting.

Post–ide-cel salvage strategies included anti-BCMA bispecific antibodies (BsAbs; n=79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n=12), triplet combinations incorporating an immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n=40), and other regimens (n=23). Overall outcomes were poor, with a median progression-free survival (PFS) of 3.48 months (95% CI, 2.6–6.37) and median overall survival (OS) of 12.12 months (95% CI, 6.6–not reached).

Patients treated with BsAbs achieved a higher overall response rate (ORR ≥PR) compared with non-BsAb regimens (36% vs 13%, P = .002). Notably, non-BCMA–targeted BsAbs demonstrated superior efficacy relative to anti-BCMA BsAbs, with significantly higher ORR (67% vs 30%, P = .018), longer median PFS (9.2 vs 3.81 months, P = .035), and improved median OS (19.48 vs 8.41 months, P = .034). These findings suggest that target switching beyond BCMA may overcome resistance mechanisms emerging after BCMA-directed CAR T-cell therapy.

Adverse prognostic factors included early relapse (≤6 months) following ide-cel (OS 5.95 vs 12.58 months, P = .040), presence of extramedullary disease (OS 6.28 vs 13.8 months, P = .033), and receipt of more than three prior lines of therapy.

In summary, outcomes after ide-cel relapse remain suboptimal. Anti-BCMA BsAbs provide limited benefit, particularly in early relapsers, whereas non-BCMA–targeted bispecific antibodies appear to offer improved clinical efficacy. These data support diversification of antigen targets as a rational post–CAR T therapeutic strategy and highlight the need for optimized sequencing approaches in this high-risk population.

"Increasing Trends of Minimal Residual Disease Measurement in Trials Focusing on Multiple Myeloma Treatment: A Systematic Analysis of Clinical Research Design From 2014 to 2025"

M. Choon-Quinones, G. D. Obeng, B. Asiedu-Ayeh, et al., “Increasing Trends of Minimal Residual Disease Measurement in Trials Focusing on Multiple Myeloma Treatment: A Systematic Analysis of Clinical Research Design From 2014 to 2025,” European Journal of Haematology (2026): 1–9, https://doi.org/10.1111/ejh.70133.  February 15, 2026. 

This comprehensive registry-based analysis evaluated the integration of minimal residual disease (MRD) as an endpoint in multiple myeloma (MM) clinical trials registered on ClinicalTrials.gov between 2014 and 2025. A total of 1,336 interventional and observational therapeutic studies met inclusion criteria.

Among interventional trials, 86.4% reported conventional therapy response outcomes, whereas 30.9% incorporated MRD assessment. The use of MRD increased markedly over time, from 6.7% of trials in 2014 to 56.8% in 2025, reflecting its growing clinical and regulatory relevance. Notably, nearly half of trials in recruiting (46.0%) or not yet recruiting (46.8%) phases included MRD as an outcome, underscoring its prospective incorporation in contemporary trial design.

Within studies evaluating MRD, 28.4% designated it as a primary endpoint, while 7.5% used MRD adaptively to guide therapeutic decision-making, signaling a shift toward response-adapted strategies. Most trials employed next-generation flow cytometry or next-generation sequencing with a sensitivity threshold of 10⁻⁵. However, heterogeneity in methodology, reporting standards, and endpoint definitions remains a challenge.

Overall, MRD has transitioned from an exploratory biomarker to a central efficacy endpoint in MM clinical research. Despite substantial expansion in its adoption, coordinated evidence generation, methodological standardization, and regulatory harmonization—particularly with evolving European Medicines Agency (EMA) and health technology assessment (HTA) frameworks—are needed. Future trial design should incorporate patient-reported outcomes and emerging noninvasive MRD approaches (e.g., peripheral blood–based assays) to enhance clinical applicability, regulatory acceptance, and health policy integration.

"Daratumumab or active observation for asymptomatic biochemical relapse in patients with multiple myeloma"

Jamroziak K, Dytfeld D, Kubicki T, Dutka M, Wróbel T, Giannopoulos K, et al. Daratumumab or active observation for asymptomatic biochemical relapse in patients with multiple myeloma. Br J Haematol. 2026; 00: 1–10. https://doi.org/10.1111/bjh.70373  February 17, 2026.  

The PREDATOR-BR trial is a randomized, multicenter study evaluating whether early intervention at biochemical progression—prior to symptomatic relapse—improves outcomes in multiple myeloma. Ninety-two patients meeting criteria for biochemical progression, but not significant paraprotein relapse (SPR), were randomized to daratumumab monotherapy or observation.

The primary endpoint was event-free survival (EFS), defined as time to clinical relapse, SPR, or death. At a prespecified interim analysis with a median follow-up of 16.7 months, daratumumab significantly prolonged EFS compared with observation (median 28.9 vs 4.0 months; HR 0.25, 95% CI 0.14–0.43). The overall response rate was markedly higher in the treatment arm (61.0%) than in the observation arm (6.8%; p < 0.0001).

Early treatment was also associated with a substantial overall survival benefit: 24-month overall survival was 100% with daratumumab versus 70.5% with observation (HR 0.04, 95% CI 0.00–0.34). Treatment demonstrated a manageable safety profile and did not adversely affect quality of life.

These findings suggest that pre-emptive therapy with daratumumab during asymptomatic biochemical relapse may significantly delay clinical progression and improve survival, challenging the conventional strategy of waiting for symptomatic relapse before initiating treatment.

"The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D"

Riedhammer, C., Truger, M., Lee, H. et al. The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D. Leukemia (2026). https://doi.org/10.1038/s41375-026-02889-3  February 17, 2026.   

This multi-center study defines and molecularly characterizes hepta-refractory multiple myeloma (MM)—a newly recognized end-stage entity resistant to CD38 antibodies, two immunomodulatory drugs (IMiDs), two proteasome inhibitors (PIs), and both BCMA- and GPRC5D-directed immunotherapies.

Among 37 patients meeting this definition, outcomes were extremely poor. Median overall survival was 12.8 months, and progression-free survival across successive salvage lines ranged from only 2.7 to 3.7 months, underscoring profound therapeutic resistance.

Whole-genome sequencing (WGS) revealed high genomic complexity, with frequent biallelic tumor suppressor gene alterations, particularly involving TP53, consistent with aggressive, apoptosis-resistant biology. Resistance-associated genomic alterations were common: 71% of patients had IMiD-related alterations, 41% BCMA-related, 35% GPRC5D-related, and 12% CD38-related changes. Notably, nearly one-third exhibited concurrent loss of both BCMA (TNFRSF17) and GPRC5D, indicating antigen escape across multiple immunotherapeutic targets.

Sequential WGS demonstrated branching clonal evolution within individual patients, with multiple distinct TNFRSF17 and GPRC5D variants arising over time. These findings suggest a reservoir of persistent subclones capable of ongoing mutational diversification, even after deep clinical remissions. Immunohistochemistry (IHC) confirmed BCMA protein loss due to biallelic TNFRSF17 genomic events but also identified cases of antigen loss through non-genetic mechanisms. Importantly, BCMA expression status correlated with benefit from BCMA re-treatment, supporting its potential role as a predictive biomarker.

Overall, hepta-refractory MM is characterized by extreme genomic instability, multi-antigen loss, and rapid clinical progression. These findings highlight the urgent need for novel therapeutic strategies and broader diagnostic frameworks incorporating integrated genomic sequencing and IHC to guide treatment decisions in this ultra-refractory population.

"Targeting BCMA in multiple myeloma with a trifunctional NK cell engager"

Alexandre Tang, Laurent Gauthier, Elisa Zaghi, Jochen Beninga, Céline Amara, Alexandra Basset, Benjamin Rossi, Dorothée Bourges, Céline Nicolazzi, Pauline Rettman, Valérie Couturier, Norbert Zombori, Laura Mendez, Yu Qiu, Joseph Batchelor, Audrey Blanchard-Alvarez, Franceline Guillot, Marilyn Giordano, Nicolas Gourdin, Ariane Morel, Cyrille Touzeau, Catherine Pellat-Deceunynck, Emilie Narni-Mancinelli, Yannis Morel, Valeria Fantin, Eric Vivier, Angela Virone-Oddos, Marielle Chiron, Targeting BCMA in multiple myeloma with a trifunctional NK cell engager, Cell Reports Medicine, 2026, 102628, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2026.102628. February 17, 2026.    

This study describes the preclinical development of SAR445514 (SAR’514), a trifunctional natural killer cell engager (NKCE) targeting B cell maturation antigen (BCMA) for the treatment of multiple myeloma (MM).

Given the limitations of current T cell–redirecting therapies—including cytokine release syndrome and durability challenges—NKCEs represent a complementary immunotherapeutic strategy with potentially improved safety and distinct mechanisms of action. SAR’514 was engineered to co-engage NKp46 and FcγRIIIa (CD16a) on natural killer (NK) cells while simultaneously binding BCMA on myeloma cells. After evaluating multiple molecular configurations with varying BCMA and NKp46 valencies, a monovalent format was selected based on superior antibody-dependent cellular cytotoxicity (ADCC).

In vitro and in vivo models demonstrated potent, selective anti-myeloma activity. SAR’514 outperformed other FcγRIIIa-directed immune cell engagers and induced minimal cytokine release compared with BCMA-targeted T cell engagers, supporting a potentially improved therapeutic index.

Ex vivo analyses using NK cells from patients with MM confirmed robust NK activation and effective cytotoxicity against autologous malignant plasma cells, including samples resistant to standard-of-care therapies. These findings suggest that SAR’514 can overcome resistance mechanisms while maintaining a favorable cytokine profile.

Overall, SAR’514 represents a rationally engineered NK cell–redirecting platform with strong preclinical efficacy and reduced inflammatory signaling, supporting its continued clinical development as a next-generation immunotherapy for multiple myeloma.

"Anti-myeloma activity of the CXCR4 antagonist WZ811"

Cholujova, D., Csicsatkova, N., Valuskova, Z. et al. Anti-myeloma activity of the CXCR4 antagonist WZ811. J Mol Med 104, 45 (2026). https://doi.org/10.1007/s00109-026-02650-4  February 17, 2026. 

This study investigates the therapeutic potential of WZ811, a CXCR4 antagonist, in multiple myeloma (MM) by targeting the CXCR4-CXCL12 signaling axis, which mediates interactions between malignant plasma cells (PCs) and the bone marrow microenvironment.

Analysis showed that CXCR4 is upregulated on MM cell lines and patient-derived plasma cells during both premalignant and active disease stages compared with normal PCs. Treatment with WZ811 reduced the viability of MM PCs and cell lines, although stromal and microenvironmental cells exhibited some resistance.

Mechanistically, WZ811 induced MM cell death through mitochondrial membrane disruption, phosphatidylserine externalization, caspase activation, increased autophagy protein levels, and cell cycle arrest at G0/G1. Importantly, WZ811 eliminated the MM stem cell–like side population, suggesting it may target disease-initiating cells. WZ811 also modulated the microenvironment by increasing CXCL12 and extracellular matrix components, including collagen IV and laminin.

In vivo studies demonstrated that WZ811 decreased tumor burden and improved survival. Drug combination studies revealed synergistic activity with doxorubicin, dexamethasone, bortezomib, lenalidomide, and pomalidomide, while antagonism was observed with carfilzomib, indicating selective combination strategies for clinical application.

Overall, these results highlight WZ811 as a promising anti-MM agent that disrupts tumor-microenvironment interactions, induces apoptosis in malignant plasma cells, and may complement existing therapies, supporting its further clinical development in multiple myeloma.

"MyCARdiac score: integrating cardiac imaging and biomarkers to predict outcomes in RRMM patients receiving cilta-cel"

Wiemers, T.C., Grieb, N., Ferle, M. et al. MyCARdiac score: integrating cardiac imaging and biomarkers to predict outcomes in RRMM patients receiving cilta-cel. Leukemia (2026). https://doi.org/10.1038/s41375-026-02887-5 February 17, 2026. 

This study evaluates the impact of baseline cardiac health on outcomes in patients with relapsed/refractory multiple myeloma (RRMM) receiving Cilta-cel CAR T-cell therapy and introduces the MyCARdiac score, a composite metric integrating echocardiographic, CT, and NT-proBNP parameters for improved risk stratification.

Seventy-two consecutive patients were analyzed, with a median age of 65.3 years and a median of seven prior therapies. Preexisting cardiac disease was present in 32% of patients, and 63% had cardiac risk factors. During follow-up, only 5.6% experienced adverse cardiac events, suggesting low overall cardiotoxicity.

Baseline echocardiographic measures of left ventricular remodeling—LVPWd, LVM-Index, LVEF—as well as coronary artery calcification (CAC) score and NT-proBNP levels, were associated with shorter progression-free survival (PFS) and, for select measures, overall survival (OS). Cut-offs for high-risk classification were defined as LVPWd >12 mm, LVM-Index >115 g/m², CAC score >3, NT-proBNP >693 ng/mL, and LVEF <51%.

The MyCARdiac score classified patients as high-risk if at least two parameters exceeded these thresholds. High-risk patients had higher disease burden (sBCMA, extramedullary disease) and more pronounced hematologic toxicities (early and late thrombocytopenia and neutropenia) after CAR T-cell infusion. High-risk status was also associated with impaired CAR T-cell expansion in CD3+ and CD4+ subsets and lower treatment response rates, while cytokine release syndrome was unaffected.

Survival analysis showed that high-risk patients had significantly reduced PFS and OS compared to low-risk patients. The MyCARdiac score outperformed the HFA-ICOS assessment for PFS stratification, highlighting its potential clinical utility.

In summary, baseline markers of left ventricular remodeling, subclinical congestion, and atherosclerosis provide independent prognostic information in RRMM patients undergoing CAR T-cell therapy. The MyCARdiac score identifies patients with more aggressive disease, impaired CAR T-cell expansion, and inferior outcomes, supporting routine cardiac assessment to refine risk stratification before CAR T-cell therapy.

These findings warrant external validation and further studies to explore the relationship between cardiac health, disease burden, and treatment response in broader patient populations.

"IMS-IMWG 2025 consensus genomic staging predicts outcomes with daratumumab-based quadruplet regimens for NDMM"

Kylee H. Maclachlan, Carlyn Rose Tan, Tala Shekarkhand, Colin J. Rueda, Andriy Derkach, Hamza Hashmi, Hani Hassoun, Urvi A. Shah, Malin L Hultcrantz, Alexander M. Lesokhin, Sham Mailankody, Francesco Maura, Maximillian Merz, Ross S. Firestone, Eric M. Jurgens, Kevin C. Miller, Sridevi Rajeeve, Sergio A. Giralt, Gunjan L. Shah, Michael Scordo, Heather J. Landau, Yanming Zhang, Robert Cimera, Maria E. Arcila, Neha Korde, Saad Z. Usmani; IMS-IMWG 2025 consensus genomic staging predicts outcomes with daratumumab-based quadruplet regimens for NDMM. Blood Adv 2026; bloodadvances.2025018537. doi: https://doi.org/10.1182/bloodadvances.2025018537  February 17, 2026. 

This study evaluates the applicability of the IMS-IMWG consensus genomic staging (CGS) in predicting outcomes for newly diagnosed multiple myeloma (NDMM) patients receiving daratumumab-based quadruplet induction therapy.

The analysis included 503 NDMM patients treated at Memorial Sloan Kettering Cancer Center, with a median follow-up of 2.2 years (maximum 7.9 years). The CGS classified 31% of patients as high-risk (HR) by incorporating TP53 mutations and co-occurrence of IgH translocations with chromosome 1 abnormalities, providing improved delineation of intermediate-risk patients compared with prior prognostic scores.

While CGS status did not predict early minimal residual disease (MRD) negativity, with similar rates in HR and standard-risk (SR) patients, it strongly predicted progression-free survival (PFS). Median PFS was 2.6 years for HR patients versus not reached for SR patients (p < 0.0001). Importantly, CGS risk remained predictive even among patients achieving MRD-negativity following autologous stem cell transplantation.

In conclusion, the IMS-IMWG CGS provides a robust framework for standardizing risk assessment and clinical trial design in NDMM, but MRD-guided trial designs should also account for genomic risk to optimize patient stratification and treatment decisions.

"Growth differentiation factor 15 promotes the malignant progression of multiple myeloma via activation of PI3K/Akt/NF-κB signaling pathway"

Fan, H., Wu, Y., Peng, Y. et al. Growth differentiation factor 15 promotes the malignant progression of multiple myeloma via activation of PI3K/Akt/NF-κB signaling pathway. J Transl Med (2026). https://doi.org/10.1186/s12967-026-07861-4  February 17, 2026.  

This study investigates molecular drivers of extramedullary disease (EMD) in multiple myeloma (MM) and identifies potential therapeutic targets.

Using bioinformatics analyses on datasets GSE146649 and GSE24870, the researchers identified four prognostic biomarkers—BIRC3, PRDX1, BCAP31, and GDF15—associated with MM proliferation and metastasis. GDF15 emerged as the key gene for further study, with serum levels significantly elevated in MM patients with EMD compared to patients without EMD and healthy controls.

Functional studies demonstrated that GDF15 promotes MM cell migration and invasion by activating the PI3K/Akt/NF-κB signaling pathway, which upregulates CXCR4 and MMP9. Inhibition of GFRAL, the receptor for GDF15, reversed these effects, and treatment with the Akt inhibitor uprosertib blocked GDF15-driven CXCR4 and MMP9 expression.

In conclusion, GDF15 contributes to MM progression and EMD development by enhancing migratory and invasive capacities through the PI3K/Akt/NF-κB pathway. These findings suggest that GDF15 represents a potential therapeutic target for controlling extramedullary spread in multiple myeloma.

"Corticosteroids ameliorate CAR T-cell-induced cytokine-release syndrome without inhibiting multiple myeloma treatment"

Amatya C, Weissler KA, Lam N, Natrakul DA, Brudno JN, Cutmore LC, et al. Corticosteroids ameliorate CAR T-cell-induced cytokine-release syndrome without inhibiting multiple myeloma treatment. Journal for ImmunoTherapy of Cancer. 2026;14:e012437. https://doi.org/10.1136/jitc-2025-012437  February 17, 2026.  

This study examines the use of dexamethasone to manage cytokine-release syndrome (CRS) during CAR T-cell therapy for multiple myeloma (MM) without compromising anti-tumor activity.

The researchers developed a preclinical CRS model including three cell types: monocyte-lineage cells (THP-1), anti-BCMA CAR T cells, and BCMA+ MM cells. Adding THP-1 cells increased key CRS cytokines, including IL-6 and MCP-1. In mice engrafted with THP-1 and bioluminescent BCMA+ MM cells, CAR-BCMA therapy effectively reduced tumor burden but induced CRS-like symptoms.

Dexamethasone treatment on days 1, 3, and 5 after CAR T-cell infusion ameliorated CRS and unexpectedly accelerated MM clearance. Mice receiving CAR-BCMA plus dexamethasone had higher levels of splenic CAR T cells than those receiving CAR-BCMA alone, indicating that corticosteroid administration did not impair CAR T-cell expansion. Clinical observations in four patients mirrored these findings, with CAR+ cell levels continuing to rise after corticosteroid initiation.

In summary, dexamethasone can control CRS while preserving or enhancing CAR T-cell anti-myeloma activity, supporting further clinical research to optimize corticosteroid regimens in CAR T therapy.

Trial registration: NCT03602612.

"Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis"

Spataro, F., Armentaro, G., Di Gioia, G. et al. Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis. Leukemia (2026). https://doi.org/10.1038/s41375-026-02880-y  February 17, 2026.   

This systematic review and meta-analysis evaluated the impact of frailty on severe infection risk in newly diagnosed multiple myeloma (NDMM) patients who are ineligible for autologous stem cell transplantation (ASCT). Frailty was assessed using various tools, including the IMWG Frailty Index, Simplified Frailty Score, and DynaFiT, across five studies comprising 1,663 patients with a mean age of 73.6 years.

The analysis showed that frail patients had a significantly higher risk of grade 3–4 infections compared with non-frail (fit plus intermediate) patients. The pooled risk ratio (RR) was 0.77 (95% CI: 0.65–0.92) for non-frail versus frail patients, indicating a 23% lower infection risk in the more robust population. Subgroup analyses revealed that fit patients had a lower, though not always statistically significant, infection risk compared to frail patients (RR = 0.67), while intermediate patients had an RR of 0.86 versus frail patients. Comparisons between fit and intermediate groups showed more variability (RR = 0.85), and in some studies fit patients paradoxically experienced higher infection rates than intermediate patients, highlighting limitations of current frailty classifications.

Meta-regression suggested that disease stage (ISS stage III) contributed modestly to infection risk variability, but overall it was not a reliable predictor. Importantly, the study emphasizes that frailty remains a critical factor for infection susceptibility due to impaired immunity, treatment-related immunosuppression, and overall poorer health.

Clinical implications include the early identification of frail and intermediate patients to implement preventive strategies such as antimicrobial prophylaxis, immunoglobulin replacement, and vaccination, while recognizing the need for periodic frailty reassessment. Limitations of the analysis include heterogeneous frailty tools, incomplete reporting of immunoglobulin supplementation, and antibiotic prophylaxis data.

In conclusion, frailty strongly influences infection risk in non-transplant-eligible NDMM patients, but existing scoring systems are imperfect. Future research should refine frailty assessments and develop targeted supportive care strategies to reduce infectious complications and improve patient outcomes.

"Lesion-level dual-tracer PET biomarkers predict prognosis in multiple myeloma treated with CXCR4-directed radiopharmaceutical therapy"

Xue, S., Kraus, S., Enke, J.S. et al. Lesion-level dual-tracer PET biomarkers predict prognosis in multiple myeloma treated with CXCR4-directed radiopharmaceutical therapy. Eur J Nucl Med Mol Imaging (2026). https://doi.org/10.1007/s00259-026-07814-5  February 18, 2026. 

This study investigated dual-tracer PET/CT imaging biomarkers to predict response and survival in patients with relapsed or refractory multiple myeloma undergoing CXCR4-directed radiopharmaceutical therapy. Twenty-two patients underwent both CXCR4-directed [⁶⁸Ga]Ga-PentixaFor PET/CT and [¹⁸F]FDG-PET/CT prior to therapy. Lesion-level features were extracted using a deep learning pipeline with automated segmentation and concordance analysis between tracers, incorporating anatomical location (medullary versus extramedullary) and volumetric overlap. Metrics included SUVmean, total lesion glycolysis, surface-standardized maximum inter-lesion distance, and CXCR4-positive volumes, alongside demographic, laboratory, and cytogenetic variables. Responders to therapy had lower FDG uptake in medullary and extramedullary concordant lesions, which ranked among the top predictive features. Shorter overall survival was associated with higher FDG total lesion glycolysis in medullary concordant lesions, greater inter-lesion distances, and higher CXCR4-positive medullary tumor volume. High-risk cytogenetics and selected extramedullary CXCR4-dominant discordant lesions also contributed to response prediction, while body mass index showed a modest inverse correlation with early mortality at six months. Overall, lesion-level quantification of FDG and CXCR4 uptake, together with spatial tumor distribution, provided predictive and prognostic information for patients considered for CXCR4-directed therapy. FDG uptake in medullary concordant lesions was linked to both response and survival, while CXCR4-positive volume and lesion dispersion added complementary survival information. These findings suggest that concordance-aware dual-tracer PET/CT analysis could improve patient selection and risk stratification for CXCR4-directed radiopharmaceutical therapy, although the results are hypothesis-generating and require prospective validation in larger cohorts.

"An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma"

Xin, X., Fan, C., Sheng, R. et al. An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma, with a brief overview of novel therapeutic strategies. Clin Exp Med (2026). https://doi.org/10.1007/s10238-026-02050-5  February 18, 2026. 

Monoclonal gammopathies form a continuum from monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma, driven by primary cytogenetic lesions, secondary genomic events, and epigenetic remodeling within a permissive bone marrow microenvironment. Traditional biomarkers, including serum M-protein and free-light-chain ratios, provide useful but incomplete prognostic information, as they fail to capture spatial heterogeneity and temporal clonal dynamics. Recent advances highlight circulating tumor cells, minimal residual disease assessment via next-generation flow and sequencing, and liquid biopsy approaches as minimally invasive tools that improve risk stratification and anticipate malignant progression. Therapeutic strategies have evolved from melphalan-based chemotherapy and autologous stem cell transplantation to triplet and quadruplet regimens incorporating immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, while next-generation immunotherapies such as BCMA-directed CAR T cells, bispecific antibodies, and cereblon E3 ligase modulators achieve unprecedented depth of response. Despite these advances, major challenges remain, including predicting individual progression in precursor states, overcoming drug resistance and relapse, managing therapy-related toxicities, and ensuring equitable access to advanced therapies. Integrating multi-omics profiling, artificial intelligence–based analytics, and dynamic biomarkers offers the potential to transform the natural history of monoclonal gammopathies, shifting outcomes from inevitable progression toward durable remission and potential cure. This review outlines the biological continuum driving disease progression from MGUS and smoldering multiple myeloma to multiple myeloma and summarizes recent advances in molecular diagnostics and novel therapeutic strategies within this context.

"An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma, with a brief overview of novel therapeutic strategies"

Xin, X., Fan, C., Sheng, R. et al. An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma, with a brief overview of novel therapeutic strategies. Clin Exp Med (2026). https://doi.org/10.1007/s10238-026-02050-5  February 18, 2026. 

Monoclonal gammopathies represent a spectrum of disease that progresses from monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma, driven by primary cytogenetic lesions, secondary genomic events, and epigenetic changes within a permissive bone marrow microenvironment. Traditional biomarkers, such as serum M-protein and free-light-chain ratios, offer useful but incomplete prognostic insight because they do not reflect spatial heterogeneity or the dynamics of clonal evolution over time. Emerging tools, including circulating tumor cells, minimal residual disease assessment via next-generation flow and sequencing, and liquid biopsy approaches, provide minimally invasive ways to refine risk stratification and anticipate disease progression. Therapeutic approaches have evolved from melphalan-based chemotherapy and autologous stem cell transplantation to triplet and quadruplet regimens combining immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, while next-generation immunotherapies—including BCMA-directed CAR T cells, bispecific antibodies, and cereblon E3 ligase modulators—deliver unprecedented depth of response. Despite these advances, major challenges remain, including predicting progression in individual precursor states, overcoming drug resistance and relapse, managing therapy-related toxicities, and ensuring equitable access to advanced therapies across diverse patient populations. The integration of multi-omics profiling, artificial intelligence–based analytics, and dynamic biomarkers has the potential to transform the natural course of these disorders, shifting monoclonal gammopathies from inevitable progression toward durable remission and possible cure. This review explores the biological continuum underlying disease evolution from MGUS and smoldering multiple myeloma to multiple myeloma and provides an overview of recent advances in molecular diagnostics and innovative therapeutic strategies.

"Excess Risk of Monoclonal Gammopathy in Patients With Gaucher Disease"

M. Istaiti, K. Thoren, D. Kazandjian, et al., “Excess Risk of Monoclonal Gammopathy in Patients With Gaucher Disease,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70240.  February 18, 2026.  

Gaucher disease is a rare autosomal recessive lysosomal storage disorder caused by deficiency of glucocerebrosidase, leading to accumulation of glucosylceramide in macrophages. It is classically associated with hepatosplenomegaly, hypersplenism, and skeletal involvement, but it is increasingly recognized as a multisystem disorder with manifestations stemming from immune, inflammatory, and metabolic dysregulation. The potential link between Gaucher disease and malignancies, particularly hematologic cancers, has been debated for over three decades, causing concern for patients and families. Early registry-based analyses from the International Collaborative Gaucher Group suggested an association with multiple myeloma and an increased prevalence of monoclonal gammopathies, though interpretation was limited by referral bias, detection bias, and over-surveillance. Because multiple myeloma is typically preceded by monoclonal gammopathy of undetermined significance, estimating MGUS prevalence in Gaucher disease has become a key focus, but prior studies relied on small, selected cohorts or retrospective data, with no systematic screening using standardized assays.

In the current study, we conducted a large cross-sectional analysis of 510 patients with Gaucher disease, including 411 adults, using uniform high-quality testing at an international myeloma reference laboratory. Monoclonal gammopathy was identified in 126 adults (30.6%) and 13 pediatric patients (13.1%). Among adults, 43 had MGUS confirmed by immunofixation, while 83 had light-chain MGUS without detectable intact immunoglobulin. Adults with MGUS or LC-MGUS were older, more likely to carry mild genotypes, had higher serum creatinine, and lower hemoglobin. Age emerged as the only independent predictor of MGUS and LC-MGUS, and the prevalence of combined monoclonal gammopathy increased with age, driven mainly by MGUS, while LC-MGUS prevalence remained relatively constant around 20%.

A longitudinal analysis of 68 adults with paired serum samples showed that MGUS and LC-MGUS appeared, persisted, or regressed regardless of treatment initiation or duration, indicating that Gaucher-specific therapy did not consistently influence the presence or evolution of monoclonal gammopathy. The study demonstrated that myeloma precursor states are more than tenfold more common in Gaucher disease than in the general population, with prevalence rising from approximately 20% under age 40 to nearly 50% in individuals over 60. These findings highlight that adults with Gaucher disease, particularly those diagnosed young, may live many years with MGUS, facing a prolonged cumulative risk of progression to multiple myeloma.

The biological mechanisms underlying MGUS and LC-MGUS in Gaucher disease remain incompletely understood. Chronic immune activation, cytokine dysregulation, and alterations in the bone marrow microenvironment likely promote clonal plasma cell survival, and antigenic stimulation from lipids such as saposin C or Lyso-Gb1 may contribute. However, no association between Lyso-Gb1 levels and monoclonal gammopathy was observed in this cohort.

Our findings support current consensus guidelines recommending routine screening and longitudinal monitoring for monoclonal gammopathy in Gaucher disease. Standard anti-myeloma therapy should be administered alongside enzyme replacement therapy to optimize marrow reserve and treatment tolerance if progression occurs. Conversely, Gaucher disease should be considered in patients presenting with MGUS who have cytopenias, organomegaly, bone pain, or unexplained bleeding. The study’s strengths include systematic, unbiased screening of consecutive patients using sensitive, uniform assays at a reference laboratory, though limitations include limited longitudinal follow-up and a single-center design. Classification of LC-MGUS relied on current free light chain reference ranges, which may evolve, but this does not alter the principal conclusions.

In conclusion, more than 30% of adults with Gaucher disease were found to have MGUS or LC-MGUS, independent of treatment status, emphasizing the need for routine screening and monitoring. Long-term studies are needed to clarify progression rates to multiple myeloma and to better characterize clinical outcomes, treatment responses, and toxicity profiles. Insights from the Gaucher disease-MGUS association may also inform broader strategies for understanding and managing monoclonal gammopathies beyond Gaucher disease.

"A critical analysis of the IMWG multiple myeloma complete response criterion in the era of mass spectrometry"

Puig, N., Agulló, C., Paiva, B., Cedena, M.-T., Rosiñol, L., Contreras, T., Martínez-López, J., Oriol, A., Blanchard, M.-J., Ríos-Tamayo, R., Sureda, A., Lakhwani, S., de la Rubia, J., Cabañas, V., de Arriba, F., Paricio, M., Iñigo, M.-B., González-Calle, V., Ocio, E.M., Castro, S., Bargay, J., Bladé, J., San Miguel, J.F., Lahuerta, J.-J. and Mateos, M.V. (2026), A critical analysis of the IMWG multiple myeloma complete response criterion in the era of mass spectrometry. HemaSphere, 10: e70301. https://doi.org/10.1002/hem3.70301  February 18, 2026. 

In multiple myeloma, achieving a complete response (CR) represents a key clinical milestone, reflecting a substantial reduction in disease burden. According to the International Myeloma Working Group criteria, CR is defined by four elements: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas, and less than 5% plasma cells in bone marrow aspirates. The clinical relevance of urine immunofixation has been questioned, and the utility of bone marrow plasma cell counting in patients with unconfirmed CR based on negative serum immunofixation remains unclear. In this context, mass spectrometry (MS) offers a highly sensitive, non-invasive marker that may provide a more accurate assessment of disease status.

This study analyzed 716 paired serum and bone marrow samples from 290 newly diagnosed transplant-eligible multiple myeloma patients enrolled in the GEM12MENOS65 and GEM14MAIN trials, with samples collected post-induction, after autologous stem cell transplant, post-consolidation, and after two years of maintenance. Serum was assessed using quantitative immunoprecipitation mass spectrometry, serum protein electrophoresis, and immunofixation, while first-pull bone marrow aspirates were used for morphological plasma cell counts. Analysis of the main CR-defining factors showed that neither bone marrow plasma cell count nor serum immunofixation distinguished patient groups with different median progression-free survival, whereas MS status clearly separated two cohorts with distinct outcomes.

Among the 476 samples with unconfirmed CR based on negative serum immunofixation, plasma cell counting did not differentiate patient outcomes, but MS-positive samples were associated with significantly reduced progression-free survival. Combining plasma cell counts and serum immunofixation to define conventional CR versus less-than-CR did not improve prognostic discrimination after consolidation or two years of maintenance, whereas MS positivity consistently identified patients with inferior outcomes. When analyzing plasma cell counts in sIFE-negative cases, the negative predictive value of MS was 90%, confirming that MS effectively identifies residual disease even when conventional markers are negative. Further analysis integrating conventional CR and MS results demonstrated that MS provided independent prognostic information, while conventional CR showed no relevance within MS-positive or MS-negative cohorts.

These findings indicate that bone marrow plasma cell counts at the conventional 5% cut-off provide limited clinical value in sIFE-negative patients, calling into question the need for invasive aspirates solely for determining plasma cell percentage. In contrast, MS offers a noninvasive, sensitive method to detect residual disease, identifying 22% of samples that would be missed using traditional CR criteria. Current IMWG guidelines for imaging in CR assessment, including low-dose CT or PET-CT, do not specify modality requirements for plasmacytoma evaluation, highlighting the need to revisit these criteria in light of modern diagnostic tools.

In conclusion, traditional CR criteria have important limitations, and bone marrow aspiration should primarily serve to assess measurable residual disease using validated methodologies. Mass spectrometry provides a noninvasive, accurate alternative for evaluating systemic tumor burden, and MS negativity could define a more stringent complete response category. While MS may reflect systemic burden later than MRD clearance, its integration with other noninvasive diagnostics has the potential to refine CR assessment. Future studies should validate these findings in broader patient populations, including those receiving novel immunotherapies, to optimize personalized treatment strategies and improve outcomes in multiple myeloma.

"A policy-based approach to optimize multiple myeloma treatment sequencing practices"

Pozsár, Z. R., Clavreul, S., Eriksson, L. L., Espín, J., Gay, F. M., Krauth, M. T., … Kaló, Z. (2015). A policy-based approach to optimize multiple myeloma treatment sequencing practices. Expert Review of Hematology. https://doi.org/10.1080/17474086.2026.2634278  February 18, 2026. 

As a result of major therapeutic advances that have transformed multiple myeloma into a manageable chronic condition, treatment sequencing has become increasingly complex. Current practices often reserve novel therapies for later stages of disease, although emerging evidence suggests that this approach may not consistently yield optimal long-term outcomes. Understanding the factors driving these practices and identifying strategies to strengthen evidence-informed sequencing is therefore essential. Insights from a multi-stakeholder discussion involving patient representatives, clinical experts, health technology assessment specialists, and industry participants highlighted several key drivers of current sequencing patterns, including constraints in clinical development pathways, limitations in guideline development, methodological challenges within health technology assessment, financial pressures, and the high disease burden present in advanced disease stages. Options to optimize treatment sequencing discussed by the group include innovative evidence-generation strategies, whole-disease modeling, meaningful patient involvement in decision-making, and expanding evaluation frameworks to better capture the real-world impact of therapies. Uncertainty remains central in shaping sequencing practices, emphasizing the need for more robust evidence to guide decisions and prevent suboptimal use of available treatment options. As the therapeutic landscape continues to expand, treatment sequencing will grow even more complex, necessitating coordinated international efforts. This multi-stakeholder discussion represents an initial step toward enabling such joint actions to ensure that sequencing strategies are evidence-driven, patient-centered, and adaptable to the evolving landscape of multiple myeloma care.

"YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma"

Li J, Lu Q, Zhu Z, Wang X, Chen Y, Zhang Z, et al. YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma. Journal for ImmunoTherapy of Cancer. 2026;14:e013986. https://doi.org/10.1136/jitc-2025-013986  February 18, 2026. 

Multiple myeloma remains characterized by frequent relapse despite major therapeutic advances. B-cell maturation antigen and G protein-coupled receptor class C group 5 member D have emerged as validated immunotherapeutic targets, and bispecific antibodies directed against these antigens have demonstrated meaningful clinical efficacy. However, their durability is often compromised by antigen escape, antigen heterogeneity, and immune evasion, including resistance mediated by soluble BCMA.

This study introduces YMN-V115, a novel humanized trispecific antibody engineered in a 1+1+1 configuration with single binding domains for BCMA, GPRC5D, and CD3. This design aims to enhance tumor-selective T-cell engagement through dual-antigen targeting while reducing the risk of CD3-driven off-tumor toxicity. In preclinical models, YMN-V115 demonstrated superior cytotoxic activity against multiple myeloma cells compared with corresponding bispecific antibodies, both in vitro and in vivo. Importantly, its activity was preserved under conditions of soluble BCMA saturation, indicating resistance to decoy-mediated inhibition. By simultaneously targeting BCMA-positive and GPRC5D-positive tumor subsets, YMN-V115 effectively addressed antigenic heterogeneity, resulting in enhanced T-cell activation and sustained tumor control.

These findings support YMN-V115 as a next-generation trispecific T-cell engager capable of overcoming key mechanisms of resistance in multiple myeloma, including antigen loss and immune escape. The data provide a strong rationale for further clinical development of this dual-antigen–targeting strategy as a promising therapeutic option for patients with relapsed or refractory disease.

"Antigen–IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα"

Moravej H, Rakhshandehroo T, Khan RMM, Rivet VM, Marcandalli E, Mantri SR, et al. Antigen–IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα. Journal for ImmunoTherapy of Cancer. 2026;14:e013665. https://doi.org/10.1136/jitc-2025-013665  February 18, 2026. 

Limited durability of clinical responses remains a central limitation of chimeric antigen receptor T-cell therapy, largely due to inadequate persistence and early T-cell exhaustion, particularly in multiple myeloma. CAR-enhancers (CAR-Es), which fuse tumor antigens to interleukin-2 muteins, have emerged as a targeted strategy to selectively augment CAR-T expansion and function. However, it has remained unclear whether CAR-Es are broadly effective across different tumor contexts, whether they retain activity when using patient-derived T cells, whether they can prevent exhaustion and sustain long-term persistence, and whether they selectively expand CAR-T cells in the presence of pre-existing T cells in humanized models. In addition, the relative contribution of IL-2 receptor subunits to CAR-E activity has been unresolved, particularly given that IL-2Rα (CD25) is associated both with potent antitumor immunity and with IL-2–related toxicities such as vascular leak syndrome and preferential regulatory T-cell expansion.

To address these questions, IL-2 variants with graded receptor affinities were engineered to systematically dissect signaling requirements. Multiple CAR-E constructs were evaluated across comprehensive in vitro and in vivo platforms. CAR-E activity was found to be entirely independent of IL-2Rα and strictly dependent on IL-2Rβγ signaling. A next-generation IL-2Rα-sparing CAR-E preserved full biological potency, inducing robust CAR-T expansion, sustained persistence, and effective tumor clearance even at low doses and when using CAR-T cells derived from previously treated multiple myeloma patients. These CAR-T cells resisted exhaustion and retained the capacity to re-expand months later to eliminate tumor rechallenge. In humanized mice with established endogenous T-cell populations, CAR-Es selectively expanded CAR-T cells to dominate the circulating T-cell compartment. Moreover, CAR-E exerted a dominant influence over CAR-T cell fate, overriding tumor-derived cues and enforcing consistent phenotypic and functional profiles across diverse preclinical models.

Collectively, these findings identify a lead B-cell maturation antigen–IL-2 CAR-E candidate with strong translational potential and establish IL-2Rβγ as the principal driver of CAR-E activity, while demonstrating that IL-2Rα is dispensable. The results provide a mechanistic framework for designing safer, IL-2Rα-sparing CAR-enhancers and support the development of clinically deployable adjuncts that can be integrated with approved CAR-T therapies to enhance durability, consistency, and safety of antitumor responses.

"Linvoseltamab, a BCMA-directed CD3 T-cell engager for multiple myeloma: a patient-centric option via a response-adapted dosing regimen?"

Lowy, J. A., Rogers, M. F., Avigan, Z. M., Flores, M. S., Samuel, M., Rattu, M. A., & Richter, J. (2015). Linvoseltamab, a BCMA-directed CD3 T-cell engager for multiple myeloma: a patient-centric option via a response-adapted dosing regimen? Expert Review of Hematology. https://doi.org/10.1080/17474086.2026.2634283  February 18, 2026. 

Despite substantial therapeutic advances in multiple myeloma, durable remissions remain elusive for many patients, underscoring the need for novel modalities, mechanisms of action, and rational combination strategies. Bispecific T-cell engagers targeting B-cell maturation antigen have demonstrated significant clinical activity in heavily pretreated populations. Linvoseltamab, a BCMA×CD3 bispecific antibody, recently received approval from the U.S. Food and Drug Administration and the European Medicines Agency on the basis of results from the LINKER-MM1 trial for patients with relapsed or refractory multiple myeloma who have progressed after at least four prior lines of therapy.

Linvoseltamab functions by simultaneously binding BCMA on malignant plasma cells and CD3 on T cells, thereby redirecting cytotoxic T-cell activity toward tumor cells. Clinical data demonstrate meaningful response rates in a heavily pretreated population, with pharmacokinetic properties that support a step-up dosing strategy followed by less frequent administration. Compared with other approved BCMA-directed bispecific antibodies, linvoseltamab offers a patient-centric dosing regimen and an overall manageable safety profile, including a favorable incidence and severity pattern of cytokine release syndrome. Indirect cross-trial comparisons suggest efficacy that is comparable to, and in some analyses slightly improved over, other available BCMA-targeted bispecific therapies, although such comparisons should be interpreted cautiously due to differences in study populations and trial design.

As the fourth bispecific antibody approved for relapsed or refractory multiple myeloma in patients previously exposed to four or more lines of therapy, linvoseltamab represents an important addition to the therapeutic armamentarium. Ongoing accumulation of real-world evidence will be critical to defining its optimal positioning within the evolving multiple myeloma treatment paradigm, particularly in the context of sequencing strategies and prior exposure to other BCMA-directed agents.

"Treatment patterns of bone-targeted agents for the prevention of skeletal-related events in multiple myeloma in Bulgaria: a cross-sectional chart review study"

Mihaylov, G., Ianakieva, V., Katrandzhieva, Z., Karaasenov, K., & Goranova-Marinova, V. (2026). Treatment patterns of bone-targeted agents for the prevention of skeletal-related events in multiple myeloma in Bulgaria: a cross-sectional chart review study. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2631213  February 18, 2026. 

Bone disease is a frequent and clinically significant complication of multiple myeloma, affecting approximately 80% of patients at diagnosis and substantially increasing the risk of skeletal-related events. The use of bone-targeted agents is recommended to prevent and manage these complications. This retrospective real-world study evaluated electronic health records from eight hematology clinics in Bulgaria to characterize demographic and clinical features, treatment patterns with bone-targeted agents, pain management strategies, and the incidence of skeletal-related events and osteonecrosis of the jaw among adults with myeloma-related bone disease.

A total of 732 patients were included, of whom 177 received denosumab, 440 received zoledronic acid, and 115 were treated sequentially with both agents. In the majority of patients across all cohorts (83%, 84%, and 84%, respectively), the first recorded treatment regimen incorporated a bone-targeted agent either alone or in combination with anti-myeloma therapy. The median duration of bone-targeted therapy was longest among patients treated sequentially, with a median duration of 84 days for zoledronic acid and 60 days for denosumab within this group. Bone-targeted agents were predominantly prescribed with preventive intent, as only 22%, 16%, and 30% of patients in the respective cohorts had experienced prior skeletal-related events. During treatment, new skeletal-related events occurred in 9%, 7%, and 9% of patients, respectively. Seven cases of osteonecrosis of the jaw were documented overall, with only one occurring during active bone-targeted therapy in the zoledronic acid cohort.

These findings confirm that patients with multiple myeloma remain at high baseline risk for skeletal complications. However, when bone-targeted agents are used preventively in routine clinical practice, the incidence of new skeletal-related events appears to be low, affecting fewer than 10% of treated patients. The data support the effectiveness of preventive bone-targeted therapy in reducing skeletal morbidity in real-world settings.

"Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers"

Derman, B., Jijun Liu, J., Bouchard, N., Figg, L., LaPorte, J., Goorha, S., … Baljevic, M. (2026). Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers. Current Medical Research and Opinion, 1–10. https://doi.org/10.1080/03007995.2026.2626367  February 18, 2026.  

This mixed-methods study examined real-world care models for step-up dosing of teclistamab and explored key considerations for successful implementation, particularly in community-based practices and settings adopting outpatient step-up dosing strategies. Data were collected through a structured survey, in-depth interviews, and a roundtable discussion with U.S. clinicians who had direct experience administering teclistamab in routine practice. The survey assessed institutional step-up dosing models, adverse event management approaches, and transition-of-care processes, while follow-up interviews and the roundtable provided qualitative insights into operational barriers and facilitators.

A total of 38 clinicians representing unique practices participated between March and August 2024, with 76% practicing in community-based settings and 66% having treated at least five patients with teclistamab. Among these practices, 53% implemented outpatient step-up dosing, 26% used inpatient models, and 21% referred patients externally for step-up dosing. For practices employing outpatient approaches, common patient-level eligibility criteria included the availability of caregiver support (90%), proximity to the treatment site (70%), good performance status (65%), and lower disease burden (30%). The primary triggers for inpatient admission during treatment included any grade immune effector cell–associated neurotoxicity syndrome (85%), grade 2 or higher cytokine release syndrome (70%), and abnormal vital signs (60%). Additionally, 29% of practices reported prophylactic use of tocilizumab.

These findings demonstrate that outpatient step-up dosing of teclistamab can be implemented successfully in appropriately selected patients, including within community oncology settings. The results provide practical insights into safety monitoring, patient selection, and resource utilization, offering guidance for practices seeking to adopt outpatient models to enhance access while reducing healthcare system burden and associated costs.

"Musculoskeletal Adverse Events Following BCMA CAR-T Cell Therapy in Multiple Myeloma: Clinical Characteristics and Immune Correlates"

Amber Feng, Jian Wu, Taewoong Choi, Xiaobei Wang, Tanya Bellavia, Kimberly Burcher, Lauren Jones, Daniel Schrum, Erin Eberwein, Sikai Cheng, Parker Mathews, Shaima Jabbar, Terrell Coring, Cristina Gasparetto, Cristiana Costa Chase, Gwynn Long, Suzanne Kirby, Chenyu Lin, Jonathan Huggins, Patrick Tam, Krista Rowe-Nichols, Yubin Kang, Musculoskeletal Adverse Events Following BCMA CAR-T Cell Therapy in Multiple Myeloma: Clinical Characteristics and Immune Correlates, Transplantation and Cellular Therapy, 2026, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2026.02.009. February 18, 2026.  

Chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen has transformed outcomes for patients with relapsed or refractory multiple myeloma, particularly with the commercial availability of ciltacabtagene autoleucel and idecabtagene vicleucel. While life-threatening toxicities such as cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome are well characterized, musculoskeletal adverse events remain poorly defined despite their potential to substantially impair quality of life. This single-center retrospective cohort study evaluated the incidence, clinical characteristics, temporal dynamics, and immunologic correlates of musculoskeletal adverse events following commercial BCMA-directed CAR-T therapy.

Sixty-nine consecutive patients treated between December 2022 and February 2025 with a minimum follow-up of three months were included. Musculoskeletal adverse events were defined as new-onset or worsening arthralgias, myalgias, or bone pain documented in clinical records. Comprehensive immune profiling was performed, including serial flow cytometric analysis of immune cell subsets and cytokine quantification. Twenty patients (29%) developed musculoskeletal adverse events, with a median onset of 39 days after infusion and a median duration of 61 days. Grade 3 events occurred in 30% of affected patients, most of whom required opioid analgesia and half of whom required corticosteroids. Polyarticular involvement was observed in 70% of cases, with the hip most frequently affected, followed by the knee and shoulder. Musculoskeletal adverse events occurred significantly more often in Black patients compared with other racial groups and were paradoxically associated with the absence of immune effector cell–associated neurotoxicity syndrome. Patients who developed these events had significantly lower baseline polymorphonuclear myeloid-derived suppressor cells prior to lymphodepletion and exhibited a persistent proinflammatory cytokine profile at six months post-infusion, characterized by elevated interleukin-12, tumor necrosis factor alpha, interferon gamma, and macrophage inflammatory protein-1 beta. No associations were identified with CAR-T product type, treatment response, or markers of CAR-T persistence.

These findings establish musculoskeletal adverse events as a common and under-recognized toxicity affecting nearly one-third of patients receiving BCMA-directed CAR-T therapy, often resulting in severe and prolonged morbidity. The association with reduced baseline polymorphonuclear myeloid-derived suppressor cells and sustained inflammatory cytokine elevation provides mechanistic insight and suggests opportunities for risk stratification and targeted intervention. Prospective validation and the development of standardized assessment and management strategies are warranted to mitigate this emerging toxicity.