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 August 2025 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 August 2025)
"Sequential Targeting in Multiple Myeloma: Talquetamab, a GPRC5D bispecific antibody, as a Bridge to BCMA CAR-T cell therapy"
Source
Binod Dhakal, Othman Salim Akhtar, David Fandrei, Alexandria Jensen, Rahul Banerjee, Darren Pan, Shambavi Richard, Reed Friend, Matthew James Rees, Patrick Costello, Mariola Alejandra Vazquez Martinez, Oren Pasvolsky, Charlotte B. Wagner, James A Davis, Omar A. Castaneda Puglianini, Ran Reshef, Aimaz Afrough, Danai Dima, Manisha Bhutani, Omar Nadeem, Ricardo D Parrondo, Ciara L Freeman, Lekha Mikkilineni, Shahzad Raza, Larry D. Anderson, Prashant Kapoor, Hitomi Hosoya, Saurabh Chhabra, Ariel Grajales-Cruz, Mahmoud R. Gaballa, Shonali Midha, Melissa Alsina, Douglas W Sborov, Krina K. Patel, Yi Lin, Christopher J Ferreri, Nico Gagelmann, Anupama Deepa Kumar, Doris K Hansen, Andrew J Cowan, Luciano J. Costa, Maximilian Merz, Surbhi Sidana; Sequential Targeting in Multiple Myeloma: Talquetamab, a GPRC5D bispecific antibody, as a Bridge to BCMA CAR-T cell therapy. Blood 2025; blood.2025029773. doi: https://doi.org/10.1182/blood.2025029773 August 1, 2025.
Overview
For people with relapsed or refractory multiple myeloma, CAR T-cell therapies like Carvykti® (ciltacabtagene autoleucel, or cilta-cel) and Abecma® (idecabtagene vicleucel, or ide-cel) have changed the outlook for many patients. These treatments use a patient’s own immune cells to attack myeloma cells, but making the therapy takes 6 to 8 weeks. During that time, some patients’ disease may get worse or even lead to death, which makes finding effective “bridging” treatments critical.
This study looked at whether the drug talquetamab, a bispecific antibody that targets the protein GPRC5D, could be used as a bridge before CAR T-cell therapy. Researchers reviewed records from 20 cancer centers in the U.S. and Germany. Of the 134 patients who received talquetamab, 119 were able to move on to CAR T-cell therapy (98 to cilta-cel and 21 to ide-cel). The main reasons patients did not proceed were disease progression, manufacturing issues, or personal choice. Most patients in this study had aggressive disease features, such as high-risk genetic changes or myeloma outside the bone marrow, and would not have qualified for earlier CAR T-cell clinical trials.
"Interleukin-5 is an adjunctive biomarker for engraftment syndrome in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation"
Source
Zhang XL, Pan MM, Kaminskiy Y, Jin SW, Mi JQ, Zhang WP, Xu J. Interleukin-5 is an adjunctive biomarker for engraftment syndrome in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation. Clin Immunol. 2025 Aug 1:110575. doi: 10.1016/j.clim.2025.110575. Epub ahead of print.
Overview
Autologous stem cell transplant (ASCT) is a common treatment for multiple myeloma, but it can sometimes lead to engraftment syndrome (ES), a complication that causes inflammation and other symptoms as new stem cells start to grow. ES is diagnosed based on clinical signs, since there’s no standard lab test to confirm it.
In this study, researchers followed 96 patients with newly diagnosed myeloma who underwent ASCT. About one in four developed ES. They measured levels of six immune system proteins, called cytokines, during the transplant process. While several cytokines rose during treatment, only one—interleukin-5 (IL-5)—could reliably tell the difference between patients with and without ES.
IL-5 levels on day 12 after transplant were the best single marker for ES, and the test became even more accurate when combined with two other factors: the proportion of certain immune cells (CD8+ T cells) after engraftment and whether the patient had previously received the drug daratumumab. Interestingly, IL-5 levels as early as day 6 could serve as an early warning sign, predicting ES in over 70% of patients when combined with treatment history.
These findings suggest that checking IL-5 levels—especially early after transplant—could help doctors predict and manage ES sooner, and that prior treatment with daratumumab may lower the risk of developing this complication.
"Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage"
Source
Atalla MS, Bettenhausen AL, Verse JM, Cebulla N, Krug SM, Sauer RS, Srivastava M, Bischler T, Chen JTC, Kortüm KM, Kittel RJ, Sommer C, Rittner HL. Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage. Br J Anaesth. 2025 Aug 1:S0007-0912(25)00366-6. doi: 10.1016/j.bja.2025.05.046. Epub ahead of print.
Overview
Velcade® (bortezomib is a highly effective treatment for multiple myeloma, but many patients develop a painful nerve condition called polyneuropathy while taking it. For some, the pain subsides over time, but for others, it can persist as a lasting issue. The reasons for this difference are not well understood, but one factor may be whether the drug can cross the blood-nerve barrier, a protective layer surrounding the nerves.
In this study, researchers looked at how bortezomib-related nerve pain starts and how it can resolve, using both rat models and clinical data from myeloma patients. In rats, just one cycle of bortezomib caused sensitivity to touch and cold. At the nerve level, the drug triggered changes in genes related to the body’s internal clock, the structure around nerve cells, and the immune system. Over time, healing processes helped “reseal” the nerve’s protective barrier, reverse swelling, and restore normal nerve fiber density in the skin.
Two proteins, cortactin and netrin-1, were linked to this recovery. Netrin-1, in particular, is known to help strengthen nerve barriers, and its levels increase during pain resolution in rats. However, in myeloma patients whose pain persisted, nerve fibers in the skin were reduced, and netrin-1 levels did not rise—possibly explaining why the pain did not improve.
These findings suggest that early bortezomib nerve damage mainly affects the outer parts of the peripheral nerves. Treatments that boost protective proteins like netrin-1 may help repair nerve barriers and reduce or prevent long-term nerve pain in patients taking bortezomib.
"Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma"
Source
Golmohammadi, M., Raza, S., Albayyadhi, M. et al. Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma. Blood Cancer J. 15, 130 (2025). https://doi.org/10.1038/s41408-025-01334-5 August 1, 2025.
Overview
Bispecific antibodies (BsAbs) are a new type of treatment that has shown strong results for people with relapsed or hard-to-treat multiple myeloma. These drugs work by directing the immune system to attack myeloma cells, but they can also cause significant side effects. This study combined results from 22 clinical trials published up to April 2025, including data from 2,374 patients, to better understand the safety profiles of different types of BsAbs.
The analysis compared BsAbs that target BCMA with those that target GPRC5D or FcRH5. Researchers also looked at combination treatments, such as teclistamab with talquetamab, and talquetamab with other drugs like daratumumab or pomalidomide. The average follow-up time for all patients was just under 12 months. Across all treatments, common side effects included low white blood cell counts (neutropenia), anemia, low platelets, and infections. Cytokine release syndrome (CRS)—an immune reaction often linked to these therapies—was seen in about two-thirds of patients, but severe CRS was rare.
The results showed some key differences between the two groups. BCMA-targeting BsAbs were linked to lower rates of severe CRS compared to GPRC5D/FcRH5-targeting BsAbs. On the other hand, GPRC5D/FcRH5 drugs caused fewer severe blood-related side effects than BCMA BsAbs.
Overall, BsAbs continue to prove highly effective against multiple myeloma, but each type has its own pattern of side effects. Understanding these differences can help doctors choose the right treatment for each patient and manage side effects more effectively.
"The bone marrow immune ecosystem shapes daratumumab acquired resistance in plasma cell myeloma"
Source
Wang, Y., Chen, S., Liang, Z. et al. The bone marrow immune ecosystem shapes daratumumab acquired resistance in plasma cell myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02712-5 August 1, 2025.
Overview
Darzalex® (daratumumab) is an important treatment for multiple myeloma, but even patients who respond well at first often see their disease return. This study explored why some myeloma cells become resistant to daratumumab by comparing bone marrow samples taken before treatment and after resistance developed.
Researchers used advanced tools, including single-cell RNA sequencing, to look at changes in both cancer cells and the surrounding immune environment. They found that after resistance developed, there were more CD8-positive “killer” T cells showing signs of exhaustion—meaning they were less effective at attacking cancer—and more immune signaling linked to inflammation (IFN-γ). At the same time, natural killer (NK) cells, another key cancer-fighting cell type, were fewer in number and showed more inhibitory traits. Myeloma cells themselves made less CD38, the protein targeted by daratumumab, and the bone marrow environment contained fewer immune cells overall, with the remaining cells showing higher exhaustion levels.
The team also discovered that a gene regulator called MYC became more active in resistant myeloma cells. Laboratory experiments suggested that IFN-γ, released by immune cells in the bone marrow, can activate MYC, which in turn is linked to drug resistance. When researchers compared these patterns to data from other patient groups, they found that this resistance signature was linked to worse survival outcomes.
These findings reveal how myeloma cells and their surrounding immune environment change to evade daratumumab. Targeting pathways like MYC activation or reversing immune cell exhaustion could be promising strategies to overcome resistance and improve long-term results for patients.
"Self-Assembling Multi-Antigen T Cell Hybridizers for Precision Immunotherapy of Multiple Myeloma"
Source
S. Li, J. Li, H. A. Faruque, P. Shami, B. Knoechel, J. Lohr, D. Sborov, J. Yang, J. Kopeček, Self-Assembling Multi-Antigen T Cell Hybridizers for Precision Immunotherapy of Multiple Myeloma. Adv. Healthcare Mater. 2025, e02156. https://doi.org/10.1002/adhm.202502156 August 1, 2025.
Overview
Bispecific T-cell engagers are an exciting new approach to treating multiple myeloma, but current versions can be limited in how easily they can be adapted to different patients or cancer targets. This study introduces a new, highly flexible immunotherapy platform called Multi-Antigen T-Cell Hybridizers (MATCH), designed to make cancer targeting more personalized.
MATCH works in two parts. One part finds and attaches to myeloma cells, while the other part activates T cells, the body’s immune “soldiers.” These two components are linked by special matching molecules that fit together like puzzle pieces once they are both in the body. This “assemble-on-site” approach allows doctors to pre-target cancer cells and then recruit T cells for attack, giving more control over timing and targeting.
To match each patient’s specific type of myeloma, researchers created different versions of the cancer-targeting component, each aimed at important myeloma markers such as BCMA, SLAMF7, and CD38. Any of these can be paired with the T cell–activating component, making the treatment customizable. In lab tests, MATCH successfully brought T cells to myeloma cells, formed strong connections between them, and killed the cancer cells effectively. Tests using patient bone marrow samples showed significant tumor reduction, and early animal studies found that MATCH slowed cancer growth while showing good safety and drug distribution in the body.
These results suggest that MATCH could become a versatile and personalized immunotherapy option for multiple myeloma, with the potential to target each patient’s cancer more precisely and powerfully.
"Bone marrow mesenchymal stem cell derived exosomal miR-361-5p reversed the effect of bortezomib on multiple myeloma"
Source
Lin T, Zhang Y, Hu Z, Liu S. Bone marrow mesenchymal stem cell derived exosomal miR-361-5p reversed the effect of bortezomib on multiple myeloma. Technology and Health Care. 2025;0(0). doi:10.1177/09287329251350918 August 1, 2025.
Overview
Velcade® (bortezomib) is an important first-line treatment for multiple myeloma, but over time, some patients’ cancer cells become resistant to it. This study explored how tiny molecules called microRNAs—specifically miR-361-5p—produced by bone marrow mesenchymal stem cells (BMSCs) may play a role in that resistance. These microRNAs can be packaged into small “messenger” particles called exosomes, which travel between cells and influence how they behave.
Researchers studied the effect of miR-361-5p in lab-grown myeloma cells treated with bortezomib. They found that when levels of miR-361-5p were low in the exosomes from BMSCs, myeloma cells were more likely to survive and less likely to die, even when exposed to bortezomib. This suggested that low miR-361-5p levels could protect cancer cells from the drug’s effects.
Further testing showed that miR-361-5p may work by targeting a protein called PDPK1, which is part of the PI3K/AKT/mTOR signaling pathway—a key pathway that helps cells grow and avoid death. When miR-361-5p levels were low, this pathway stayed active, making it harder for bortezomib to kill the cancer cells.
These findings suggest that restoring miR-361-5p levels, or otherwise blocking the PDPK1/PI3K/AKT/mTOR pathway, could be a strategy to overcome bortezomib resistance and make treatment more effective for people with multiple myeloma.
"METTL5 regulates SEPHS2-mediated selenoprotein synthesis to promote multiple myeloma survival and progression"
Source
Jiang, J., Zhong, F., Xiao, Z. et al. METTL5 regulates SEPHS2-mediated selenoprotein synthesis to promote multiple myeloma survival and progression. Cell Death Dis 16, 585 (2025). https://doi.org/10.1038/s41419-025-07904-6 August 2, 2025.
Overview
Researchers have discovered that a molecule called METTL5, which helps add chemical tags to ribosomal RNA, may play an important role in the growth and survival of multiple myeloma cells. Normally, ribosomal RNA helps cells make proteins, but when METTL5 levels are abnormally high—as seen in several cancers—it can change how proteins are made in ways that support tumor growth.
In this study, METTL5 levels were found to be much higher in the bone marrow of newly diagnosed myeloma patients than in healthy people or in patients whose disease was in remission. Patients with higher METTL5 levels tended to have worse outcomes. Laboratory and animal model experiments showed that METTL5 helps myeloma cells grow and survive. When METTL5 was reduced, the cells’ ability to make proteins dropped, and a key pathway related to selenium metabolism slowed down.
This selenium pathway is important because it helps cells produce selenoproteins, which protect against harmful molecules called reactive oxygen species (ROS). With lower METTL5 activity, fewer selenoproteins were made, ROS levels rose, and myeloma cells were more likely to die. The researchers also identified salvianolic acid C (SAC) as a possible drug that can block METTL5, leading to increased cancer cell death in both lab and animal studies.
These findings suggest that METTL5 is a driver of myeloma progression by altering protein production and metabolism to help cancer cells survive. Targeting METTL5—possibly with SAC—could offer a new approach to slowing or stopping multiple myeloma.
"Outcomes in frail patients receiving BCMA-directed bispecific antibodies for relapsed/refractory multiple myeloma"
Source
Benjamin Adegbite, Carlyn Rose Tan, Tala Shekarkhand, Ross S. Firestone, Eric M. Jurgens, Kevin Miller, Alexander M. Lesokhin, Gunjan L. Shah, Neha Korde, Sridevi Rajeeve, Heather J. Landau, Michael Scordo, Hani Hassoun, Kylee H. Maclachlan, Urvi A. Shah, Malin Hultcrantz, Issam S. Hamadeh, Andriy Derkach, David Nemirovsky, Sergio A. Giralt, Sham Mailankody, Saad Z. Usmani, Hamza Hashmi; Outcomes in frail patients receiving BCMA-directed bispecific antibodies for relapsed/refractory multiple myeloma. Blood Adv 2025; 9 (15): 4016–4022. doi: https://doi.org/10.1182/bloodadvances.2025015973 August 4, 2025.
Overview
Researchers have discovered that a molecule called METTL5, which helps add chemical tags to ribosomal RNA, may play an important role in the growth and survival of multiple myeloma cells. Normally, ribosomal RNA helps cells make proteins, but when METTL5 levels are abnormally high—as seen in several cancers—it can change how proteins are made in ways that support tumor growth.
In this study, METTL5 levels were found to be much higher in the bone marrow of newly diagnosed myeloma patients than in healthy people or in patients whose disease was in remission. Patients with higher METTL5 levels tended to have worse outcomes. Laboratory and animal model experiments showed that METTL5 helps myeloma cells grow and survive. When METTL5 was reduced, the cells’ ability to make proteins dropped, and a key pathway related to selenium metabolism slowed down.
This selenium pathway is important because it helps cells produce selenoproteins, which protect against harmful molecules called reactive oxygen species (ROS). With lower METTL5 activity, fewer selenoproteins were made, ROS levels rose, and myeloma cells were more likely to die. The researchers also identified salvianolic acid C (SAC) as a possible drug that can block METTL5, leading to increased cancer cell death in both lab and animal studies.
These findings suggest that METTL5 is a driver of myeloma progression by altering protein production and metabolism to help cancer cells survive. Targeting METTL5—possibly with SAC—could offer a new approach to slowing or stopping multiple myeloma.
"Performance and comparison of FLCCheck: a novel serum free light chain assay for the Auxiliary Diagnosis of Multiple Myeloma"
Source
Cao, J., Chen, X., Zhou, Y. et al. Performance and comparison of FLCCheck: a novel serum free light chain assay for the Auxiliary Diagnosis of Multiple Myeloma. Eur J Med Res 30, 706 (2025). https://doi.org/10.1186/s40001-025-02984-8 August 4, 2025.
Overview
Researchers tested a new blood test called FLCCheck to measure free light chains in people with multiple myeloma. These proteins are important for tracking the disease and deciding when treatment is needed. The study compared FLCCheck with two established tests—Freelite and N Latex FLC—using 115 samples from 72 patients.
The results showed that FLCCheck was accurate, precise, and better at avoiding interference from other proteins. It also had the strongest agreement with the N Latex FLC test, especially when measuring the κ/λ ratio, a key marker used in diagnosis and monitoring. In some cases, FLCCheck detected changes in patients’ free light chains more quickly and with greater variation than the other tests, which could make it useful for spotting treatment effects earlier.
While all three methods gave similar trends over time, the researchers stressed that they are not interchangeable. For the most reliable tracking of multiple myeloma, the same testing method should be used consistently. The team concluded that developing new and improved testing tools like FLCCheck could help doctors better monitor disease activity, guide treatment decisions, and improve patient care.
"B-cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development and Pro-Inflammatory Signatures in Myeloma Model"
Source
Tabish Hussain, Matthew D. Bramble, Bin Liu, Martin C. Abba, Marta Chesi, C. Marcelo Aldaz, B-cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development and Pro-Inflammatory Signatures in Myeloma Model, Blood Neoplasia, 2025, 100153, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100153. August 4, 2025.
Overview
Researchers have found that a gene called WWOX, which normally helps protect cells from becoming cancerous, is often lost or damaged in B cell cancers, including multiple myeloma. Loss of WWOX is linked to worse outcomes for patients. In previous studies, deleting WWOX early in B cell development in mice caused genetic instability and abnormal growth of plasma cells, similar to what happens in human disease.
In this study, scientists combined WWOX deletion with activation of the MYC gene in mice, two changes commonly seen in B cell and plasma cell cancers. These mice developed aggressive cancers, including plasmablastic plasmacytomas and lymphomas, and had significantly shorter survival compared with mice that had only MYC activation.
Looking closer at the tumor cells, the researchers found that WWOX loss triggered genetic changes and activated pathways linked to tumor growth and inflammation. The tumors also showed mutations in key cancer-related genes and in genes involved in DNA repair, along with overactive enzymes that can cause further genetic changes.
These findings show that losing WWOX can push B cells toward more aggressive cancer forms. Understanding how WWOX loss drives disease progression could help researchers develop new strategies to target high-risk myeloma and other B cell cancers.
"Management of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: position statement of the Medical and Scientific Advisory Group of Myeloma Australia"
Source
McCaughan, G., Beer, H., Bryant, C., Ho, P.J., King, T., Lee, C., Mollee, P., Prince, H.M., Spencer, A., Talaulikar, D., Vandyke, K., Weber, N., Yong, A., Harrison, S. and Quach, H. (2025), Management of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: position statement of the Medical and Scientific Advisory Group of Myeloma Australia. Intern Med J. https://doi.org/10.1111/imj.70148 August 4, 2025.
Overview
Over the past 20 years, the outlook for people newly diagnosed with multiple myeloma has improved thanks to advances in treatments. Despite these improvements, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard treatment for patients who are healthy enough to undergo the procedure.
The Medical and Scientific Advisory Group of Myeloma Australia has outlined recommendations for patients considered suitable for this approach. These guidelines provide advice on how high-dose chemotherapy and stem cell transplantation should be used as part of initial therapy, helping doctors and patients make informed decisions about the best treatment plan for newly diagnosed multiple myeloma.
"Deciphering neutrophil dynamics in the focal lesion tumor microenvironment to overcome immunosuppression in multiple myeloma"
Source
Joshua Rivera, Qi Yan, Saeed Daneshmandi, Romain Lannes, Eriko Katsuta, Jee Eun Choi, Prashant K. Singh, Ahmed Belal, Ronald Alberico, Ian Lund, Magan Schaefer, Hamza Hassan, Sarah Parker, Kenneth C. Anderson, Nikhil C. Munshi, Mehmet K. Samur, Philip L. McCarthy, Jens Hillengass, Hemn Mohammadpour; Deciphering neutrophil dynamics in the focal lesion tumor microenvironment to overcome immunosuppression in multiple myeloma. Blood 2025; blood.2025028963. doi: https://doi.org/10.1182/blood.2025028963 August 4, 2025.
Overview
Recent research has highlighted the role of certain immune cells called neutrophils in helping multiple myeloma evade the body’s defenses. Neutrophils, a type of myeloid cell, can create an immunosuppressive environment that reduces the effectiveness of immune-based treatments. This study analyzed neutrophils from bone marrow and tumor focal lesions using advanced techniques to better understand their behavior in multiple myeloma.
The researchers identified three distinct types of mature neutrophils, each with unique characteristics. One type, called TREM1+CD10+, was especially common in tumor focal lesions and showed strong immunosuppressive effects on T cells, the immune cells responsible for attacking cancer. Patients with higher levels of this neutrophil type had shorter overall survival, highlighting its impact on disease outcomes.
Importantly, the study found that targeting neutrophils with a drug that blocks CXCR2, either alone or alongside standard myeloma treatments, reduced tumor growth and improved survival in preclinical models. These findings suggest that neutrophils play a key role in protecting myeloma cells from the immune system, and therapies aimed at inhibiting neutrophil activity could make existing treatments more effective.
"Population-Based Survival Analysis of Solitary Plasmacytoma of Spine in the United States From 2000 to 2020"
Source
K. E. Agner, L. G. Comisford, A. G. Kotler, J. A. Wells, and M. C. Larkins, “Population-Based Survival Analysis of Solitary Plasmacytoma of Spine in the United States From 2000 to 2020,” Cancer Reports 8, no. 8 (2025): e70299, https://doi.org/10.1002/cnr2.70299. August 5, 2025.
Overview
Solitary plasmacytomas of the spine (SPBS) are rare tumors that can cause serious health problems and sometimes progress to multiple myeloma. This study analyzed a large national database to better understand how patient characteristics and treatment choices affect survival in people diagnosed with SPBS.
The analysis included 1,391 patients and found several factors that influenced five-year survival. Older age and higher income were linked to shorter survival, while being married was associated with better outcomes. Treatment also made a big difference: patients who received radiation therapy or had complete surgical removal of the tumor lived longer. Combining radiation with surgery led to better survival compared with radiation alone, with complete tumor removal offering the highest survival among surgical approaches.
These results suggest that using both surgery and radiation may improve outcomes for patients with SPBS, challenging current guidelines that often recommend radiation with or without surgery. Understanding these factors can help doctors and patients make more informed treatment decisions and may guide future updates to treatment recommendations.
"Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials"
Source
Maria-Victoria Mateos, Suzanne Trudel, Hang Quach, Pawel Robak, Meral Beksac, Ludek Pour, Marek Hus, Kihyun Kim, Vera Zherebtsova, Sosana Delimpasi, Tomas Jelínek, Christopher Ward, P. Joy Ho, Vladimir I. Vorobyev, Marcelo Pitombeira Lacerda, Gracia Aparecida Martinez, Ivan Spicka, Jakub Radocha, Michele Cavo, Claudio Cerchione, Chengcheng Fu, Kazuhito Suzuki, Rachel Rogers, Amy Phillips-Jones, Zhaohui Wang, Hena Baig, Jodie Wilkes, Xiaoou L. Zhou, Eric Lewis, Lydia Eccersley, Neal Sule, Prani Paka, Joanna B. Opalinska, Pralay Mukhopadhyay, Vania Tietsche de Moraes Hungria, Meletios Athanasios Dimopoulos; Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials. Blood Adv 2025; bloodadvances.2025016949. doi: https://doi.org/10.1182/bloodadvances.2025016949 August 5, 2025.
Overview
Blenrep (belantamab mafodotin, or belamaf) is a targeted therapy for relapsed or refractory multiple myeloma that has shown significant benefits when combined with standard treatments. Clinical studies DREAMM-7 and DREAMM-8 found that belamaf improved progression-free survival and, in DREAMM-7, overall survival as well. However, one of the main side effects of belamaf involves the eyes, including dry eyes, light sensitivity, irritation, and changes seen on eye exams.
To manage these ocular events, doctors used dose modifications such as delaying treatment or reducing the dose based on eye exam findings. In patients with normal vision at the start of treatment, extending the time between belamaf doses to 8–12 weeks by nine months helped control eye side effects. Most eye problems occurred during the first three months and tended to improve over time, with a median resolution time of about 12 weeks for more significant findings. Very few patients had to stop treatment because of eye issues.
Importantly, nearly all patients who responded to belamaf required some dose adjustment. Most achieved a response before a prolonged dose delay, and those who had not yet responded often achieved or deepened their response afterward. Patients who experienced at least one extended dose delay still maintained strong outcomes, with median progression-free survival of 36.6 months in DREAMM-7 and not reached in DREAMM-8. These results show that although ocular events are common, they can be effectively managed with careful dosing, allowing patients to stay on therapy and benefit from belamaf’s treatment effects.
"Refining renal response assessment in monoclonal immunoglobulin deposition disease: Challenges, limitations and need for consensus"
Source
Karam, S., Pianko, M.J. & Hassoun, H. Refining renal response assessment in monoclonal immunoglobulin deposition disease: Challenges, limitations and need for consensus. Leukemia (2025). https://doi.org/10.1038/s41375-025-02686-4 August 5, 2025.
Overview
Monoclonal immunoglobulin deposition disease (MIDD) is a rare disorder in which abnormal plasma cells or B cells produce immunoglobulin molecules that deposit in organs, most commonly the kidneys. These deposits can involve light chains, heavy chains, or both, and can cause significant organ damage. When MIDD affects the kidneys, it is considered part of a broader condition called monoclonal gammopathy of renal significance (MGRS). While MIDD often arises from plasma cell disorders, it can also be linked to other types of blood cell cancers. If untreated, MIDD can lead to end-stage kidney disease, resulting in serious health complications.
Patients with kidney involvement usually show changes in kidney function, including protein in the urine and reduced filtration rate (eGFR). The severity of kidney disease at diagnosis depends on which parts of the kidney are affected—glomeruli, tubules, or blood vessels—as well as the extent of structural damage. Many patients (20–60%) develop nephrotic syndrome, a condition marked by high protein levels in the urine, although some cases involve vascular damage with little proteinuria.
Treatment for MIDD focuses on targeting the abnormal plasma cell or B-cell clone. Research over the past two decades has shown that clone-directed therapy is both safe and effective. Patients who achieve a deep response to therapy often experience improved kidney function and longer survival. These findings highlight the importance of early diagnosis and appropriate treatment to prevent kidney failure and improve outcomes for patients with MIDD.
"Where are the immunoglobulins? A review of non-secretory multiple myeloma"
Source
Toscano, M.P., Nakashima, M.O. Where are the immunoglobulins? A review of non-secretory multiple myeloma. J Hematopathol 18, 39 (2025). https://doi.org/10.1007/s12308-025-00652-8 August 6, 2025.
Overview
Multiple myeloma (MM) is usually marked by the production of a detectable monoclonal protein in the blood or urine. However, in about 1–3% of cases, patients have non-secretory multiple myeloma (NSMM), meaning no measurable monoclonal protein or abnormal light chains are present. Advances in lab testing have changed how these cases are identified over time.
NSMM was once thought to be less aggressive than typical, secretory MM, but recent research suggests its behavior and response to treatment can differ from patient to patient. Because of these differences, managing NSMM may require a tailored approach. Current studies highlight the importance of using advanced diagnostic tools to detect and monitor NSMM, helping doctors provide more precise treatment and improve patient outcomes.
"Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma"
Source
Touzeau, C., Lipe, B., Khan, A.M. et al. Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma. Adv Ther (2025). https://doi.org/10.1007/s12325-025-03308-2 August 6, 2025.
Overview
Carvykti® (ciltacabtagene autoleucel, or cilta-cel) is a CAR-T therapy approved for patients with relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study, cilta-cel showed strong effectiveness compared with standard drug combinations in patients who had received 1–3 prior treatments. Researchers conducted a comparison with real-world treatments chosen by physicians to see how cilta-cel performs in everyday clinical practice for patients whose disease is lenalidomide-refractory.
The study looked at data from 208 patients treated with cilta-cel and compared it with 932 patients from the Flatiron Health database who received standard treatments. After adjusting for important baseline factors, cilta-cel was shown to significantly improve outcomes. Patients receiving cilta-cel had longer progression-free survival (PFS), longer time before needing the next treatment (TTNT), and better overall survival (OS) compared with the real-world group. These results remained consistent across multiple analyses.
This research highlights that cilta-cel is an effective treatment option for patients with relapsed, lenalidomide-refractory multiple myeloma. It not only delays disease progression and the need for additional therapy but also provides a meaningful survival benefit compared with typical real-world treatment choices.
"Simultaneous whole-body multi-parametric 2-[18F]FDG-PET/MRI in smoldering multiple myeloma assessment: diagnostic and prognostic impact"
Source
Jamet, B., Touzeau, C., Necib, H. et al. Simultaneous whole-body multi-parametric 2-[18F]FDG-PET/MRI in smoldering multiple myeloma assessment: diagnostic and prognostic impact. Leukemia (2025). https://doi.org/10.1038/s41375-025-02717-0 August 7, 2025.
Overview
This study looked at how well whole-body PET/MRI scans work in evaluating patients with smoldering multiple myeloma (SMM), a precursor to active multiple myeloma. Researchers wanted to see if PET/MRI could detect early disease in the bone marrow or elsewhere and predict which patients might progress to symptomatic myeloma that requires treatment. A total of 116 SMM patients underwent these advanced scans. MRI detected bone lesions in 20% of patients, compared with 9% by PET, and MRI also identified diffuse bone marrow involvement in 53% of patients versus 20% with PET.
Follow-up of 98 patients who did not initially require treatment revealed that diffuse bone marrow involvement on MRI was the strongest predictor of disease progression. Patients with this finding were significantly more likely to develop symptomatic myeloma, suggesting it could serve as a new high-risk biomarker. Additional MRI measures, such as increased peak enhancement intensity and maximum intensity time ratio, were also linked to higher risk of progression.
Overall, these results highlight the value of MRI-based imaging in identifying high-risk SMM patients. Detecting diffuse bone marrow changes before symptoms appear can help doctors determine which patients may need closer monitoring or earlier treatment to prevent disease progression.
"Differential Diagnosis of Multiple Myeloma"
Source
Miguel Dario Cantu, Weina Chen, Differential Diagnosis of Multiple Myeloma, Seminars in Diagnostic Pathology, 2025, 150944, ISSN 0740-2570, https://doi.org/10.1016/j.semdp.2025.150944. August 7, 2025.
Overview
Distinguishing multiple myeloma (MM) from certain types of B-cell lymphomas can be challenging because these cancers can look similar under the microscope, share overlapping protein markers, and present with similar symptoms. This review focuses on how doctors differentiate MM from other B-cell cancers, especially those that show plasmacytic or plasmablastic features, which can closely mimic plasma cell cancers.
The article highlights the importance of using molecular and genetic testing, along with careful clinical evaluation, to make an accurate diagnosis. It discusses aggressive plasmablastic cancers, such as extramedullary plasmablastic plasmacytomas, as well as low-grade B-cell lymphomas that show plasmacytic differentiation, including lymphoplasmacytic lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Other less common low-grade lymphomas, such as follicular lymphoma and mantle cell lymphoma, can also occasionally show plasmacytic features.
The review also covers multiple myeloma cases with CCND1:IGH genetic changes, which can resemble low-grade B-cell lymphomas, as well as post-treatment plasma cell proliferations following therapy for B-cell lymphomas. Overall, the paper emphasizes a careful combination of pathology, molecular testing, and clinical assessment to ensure the correct diagnosis, which is critical for choosing the most effective treatment.
"Optimizing Selection of Bridging Therapies Prior to CAR-T Therapy Administration for Multiple Myeloma: Clinical Pearls From an Expert Roundtable"
Source
Sikander Ailawadhi, Larry D. Anderson, Binod Dhakal, Leyla Shune, Douglas W. Sborov, Doris K. Hansen, Optimizing Selection of Bridging Therapies Prior to CAR-T Therapy Administration for Multiple Myeloma: Clinical Pearls From an Expert Roundtable, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.08.005. August 7, 2025. .
Overview
Autologous CAR-T therapies have become an important treatment option for multiple myeloma (MM), offering hope for patients with advanced disease. Before receiving CAR-T therapy, most patients are given bridging therapy to reduce tumor burden and help prepare their bodies for treatment. The choice of bridging therapy is highly individualized, depending on each patient’s disease features, prior treatments, and overall health.
While clinical trials have used specific bridging regimens, real-world practice shows a wide variety of anti-myeloma treatments being used to bridge patients to CAR-T therapy. Because of this variability, expert guidance is important to help doctors select the most appropriate bridging approach for each patient. This review outlines key factors that influence bridging therapy selection and provides practical recommendations for tailoring treatment across different patient populations.
As CAR-T therapy becomes available to more patients and referrals occur earlier in the disease course, working closely with experienced CAR-T centers will be critical. This collaboration can help ensure bridging therapy is used safely and effectively, improving outcomes for patients undergoing CAR-T treatment for MM.
"Value of serum-free light chain measurements in response and progression assessment in multiple myeloma with monoclonal protein measurable by electrophoresis"
Source
Askari, E., Dispenzieri, A., Buadi, F.K. et al. Value of serum-free light chain measurements in response and progression assessment in multiple myeloma with monoclonal protein measurable by electrophoresis. Blood Cancer J. 15, 133 (2025). https://doi.org/10.1038/s41408-025-01340-7 August 7, 2025.
Overview
Monitoring treatment response is a key part of managing multiple myeloma (MM) and developing new therapies. Measuring monoclonal proteins has long been the main way to track disease activity. The International Myeloma Working Group (IMWG) recommends including serum-free light chains (sFLC) in response assessments, especially for patients with no measurable disease by standard tests and to define a stringent complete response.
This study looked at 839 MM patients who had measurable disease using sFLC and standard serum or urine tests. Researchers found that changes in sFLC closely mirrored changes seen with standard tests, and sFLC often detected treatment response slightly earlier—on average about 1 month sooner. After just two cycles of therapy, patients showing partial response in sFLC were very likely to show a similar response on standard tests later.
Importantly, sFLC also helped track disease progression. About 12% of patients had sFLC as the only detectable marker of relapse when starting second-line therapy. Patients whose progression was identified only by sFLC had better overall survival compared with those whose progression was detected by urine M-protein. These findings support using serial sFLC measurements not just for patients with non-measurable disease, but for all MM patients, and suggest that sFLC could replace the 24-hour urine test in routine response monitoring
"Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results"
Source
Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hebraud, Cyrille Hulin, Marie C. Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jérôme Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W. C. J. van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuilleme, Pieter Sonneveld; Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results. Blood 2025; 146 (6): 679–692. doi: https://doi.org/10.1182/blood.2024027620 August 7, 2025.
Overview
Long-term results from the CASSIOPEIA study show that adding daratumumab to standard therapy significantly improves outcomes for transplant-eligible patients with newly diagnosed multiple myeloma. Patients received either daratumumab combined with Velcade® (bortezomib), Thalomid® (thalidomide), and dexamethasone (D-VTd) or VTd alone for induction and consolidation therapy. After this phase, some patients continued with daratumumab maintenance, while others were observed without further treatment.
The study found that D-VTd led to higher rates of minimal residual disease (MRD) negativity, both after induction and consolidation, compared with VTd alone. Importantly, this improvement in MRD translated into longer progression-free survival (PFS), regardless of patients’ MRD status after induction. Darzalex® (daratumumab) maintenance further increased MRD-negativity rates and extended PFS for all patients, including those with high-risk disease features.
Overall, patients who received D-VTd followed by daratumumab maintenance achieved the deepest and most sustained MRD negativity. These results demonstrate that incorporating daratumumab both during initial therapy and as maintenance provides the strongest long-term benefit, helping patients maintain remission for longer and supporting its use as a standard approach for newly diagnosed, transplant-eligible multiple myeloma.
"Myeloma: a sky full of MRD stars"
Source
Bruno Paiva, Jesús F. San-Miguel; Myeloma: a sky full of MRD stars. Blood 2025; 146 (6): 649–650. doi: https://doi.org/10.1182/blood.2025029160 August 7, 2025.
Overview
Long-term results from the CASSIOPEIA trial, as reported by Corre and colleagues, provide important insights into the role of minimal residual disease (MRD) in managing multiple myeloma (MM). This large study focused on transplant-eligible patients with newly diagnosed MM who received either standard therapy with Velcade® (bortezomib), Thalomid® (thalidomide), and dexamethasone (VTd) or VTd plus Darzalex® (daratumumab) (D-VTd), followed by a second randomization to daratumumab maintenance or observation. After a median follow-up of 80 months, the study confirmed that D-VTd induction and consolidation improved progression-free survival (PFS) and overall survival compared with VTd alone, and daratumumab maintenance further extended PFS, particularly for patients who had not received daratumumab earlier in their treatment.
The study also highlighted the importance of MRD assessment as a predictor of long-term outcomes. MRD negativity was highest and most durable in patients treated with daratumumab across all phases of therapy, and this deep response correlated strongly with prolonged PFS. Importantly, the trial compared two MRD detection methods—multiparameter flow cytometry and next-generation sequencing—and found high agreement between the two, showing that MRD can be reliably measured even in patients receiving anti-CD38 therapy. The study design ensured MRD was assessed at predefined time points for nearly all patients, providing robust and reliable data.
The analysis revealed several important observations about MRD. For instance, MRD negativity rates appeared lower when linked to complete remission (CR), likely due to the time it takes for remaining M-protein to clear from the blood. High-risk patients, such as those with t(4;14) or del(17p), achieved impressive MRD-negative rates with daratumumab maintenance, and their PFS improved to levels similar to standard-risk patients. The study also found that patients who converted from MRD-positive to MRD-negative later in therapy had slightly worse outcomes than those who achieved MRD negativity earlier, underscoring the benefit of continuing therapy after the best response is reached.
Overall, this long-term analysis demonstrates that achieving deep and sustained MRD negativity strongly predicts longer PFS in transplant-eligible MM patients. The study provides a clear example of how MRD should be assessed and reported in clinical trials, showing its value in guiding treatment decisions and helping clinicians tailor therapy to achieve the best possible outcomes.
"Optimal MRD-based end point to support response-adapted treatment cessation in newly diagnosed multiple myeloma"
Source
Smith Giri, Binod Dhakal, Natalie S. Callander, Eva Medvedova, Kelly Godby, Bhagirathbhai R. Dholaria, Susan Bal, Gayathri Ravi, Saurabh Chhabra, Rebecca W. Silbermann, Luciano Costa; Optimal MRD-based end point to support response-adapted treatment cessation in newly diagnosed multiple myeloma. Blood 2025; 146 (6): 707–716. doi: https://doi.org/10.1182/blood.2024027674 August 7, 2025.
Overview
Recent research highlights the importance of minimal residual disease (MRD) monitoring in guiding treatment decisions for multiple myeloma (MM). In a study of 221 patients who received first-line quadruplet (QUAD) therapy followed by autologous stem cell transplantation (ASCT), researchers looked at the best ways to predict which patients could safely stop treatment. Patients discontinued therapy only if they were MRD-negative by next-generation sequencing at two consecutive time points.
The study tested several short-term measures, including stringent complete response, MRD at different sensitivity levels (<10⁻⁵ and <10⁻⁶), and sustained MRD (S-MRD) assessed over two consecutive tests at least a year apart. Among these, S-MRD <10⁻⁵ emerged as the strongest predictor of progression-free survival (PFS), meaning it was the most reliable marker for identifying patients likely to remain in remission after stopping therapy. This measure also effectively predicted the risk of MRD returning or disease progressing in patients following MRD-guided treatment cessation.
These findings suggest that using sustained MRD negativity as a guide could help clinicians safely implement fixed-duration therapy in MM, allowing some patients to pause treatment without compromising long-term outcomes. This approach provides a more precise way to tailor therapy and monitor for early signs of disease resurgence.
"Sustained MRD negativity: robust, not all-powerful"
Source
Aurore Perrot, Jill Corre; Sustained MRD negativity: robust, not all-powerful. Blood 2025; 146 (6): 652–653. doi: https://doi.org/10.1182/blood.2025029342 August 7, 2025.
Overview
Recent research underscores the growing importance of minimal residual disease (MRD) monitoring in guiding treatment decisions for patients with newly diagnosed multiple myeloma (NDMM). In a study led by Giri and colleagues, sustained MRD negativity at a 10⁻⁵ threshold (S-MRD <10⁻⁵) was identified as the most reliable predictor of progression-free survival (PFS) following intensive therapy, including quadruplet induction and autologous stem cell transplantation (ASCT). This study builds on previous evidence showing that achieving MRD negativity, regardless of treatment type or disease setting, is consistently linked to better outcomes and longer survival.
A key takeaway from this work is that dynamic, repeated MRD assessments over time provide more meaningful prognostic information than a single measurement. In the study, patients had MRD testing at multiple points—after induction, after transplant, and after consolidation cycles—allowing researchers to define sustained negativity with high precision. Interestingly, the 10⁻⁵ threshold was slightly more predictive than the deeper 10⁻⁶ threshold, likely due to fewer patients reaching that deeper level of remission in this dataset, though both thresholds remain important for clinical evaluation.
The study also highlights that MRD alone is not enough to guide therapy decisions. Patients with high-risk cytogenetic abnormalities (HRCAs) may still face a higher chance of relapse even if they achieve sustained MRD negativity, emphasizing the need to consider both disease biology and MRD results when planning treatment. Conversely, patients without high-risk features who reach S-MRD <10⁻⁵ may be candidates for safely reducing or pausing therapy.
Overall, Giri et al reinforce the value of MRD as a powerful tool for personalizing myeloma care, but one that should be used alongside traditional risk factors and clinical judgment. Their findings support continued research to refine MRD-based strategies and integrate them into risk-adapted treatment plans to maximize patient outcomes.
"Efficacy, safety, and health-related quality of life in transplant-ineligible newly diagnosed multiple myeloma patients receiving bortezomib maintenance therapy: a study of the Korean Multiple Myeloma Working Party (KMMWP-174 study)"
Source
Lee JY, Jung S, Choi S, Park S-S, Kim JS, Lee J-J, Park SK, Kim HJ, Lee G-W, Park YH, Eom H-S, Kim J-A, Kim MK, Kim Y, Shin H-J, Lee HS, Kwon J, Min C-K. Efficacy, safety, and health-related quality of life in transplant-ineligible newly diagnosed multiple myeloma patients receiving bortezomib maintenance therapy: a study of the Korean Multiple Myeloma Working Party (KMMWP-174 study). Haematologica; https://doi.org/10.3324/haematol.2025.287889 [Early view]. August 7, 2025
Overview
Recent research underscores the growing importance of minimal residual disease (MRD) monitoring in guiding treatment decisions for patients with newly diagnosed multiple myeloma (NDMM). In a study led by Giri and colleagues, sustained MRD negativity at a 10⁻⁵ threshold (S-MRD <10⁻⁵) was identified as the most reliable predictor of progression-free survival (PFS) following intensive therapy, including quadruplet induction and autologous stem cell transplantation (ASCT). This study builds on previous evidence showing that achieving MRD negativity, regardless of treatment type or disease setting, is consistently linked to better outcomes and longer survival.
A key takeaway from this work is that dynamic, repeated MRD assessments over time provide more meaningful prognostic information than a single measurement. In the study, patients had MRD testing at multiple points—after induction, after transplant, and after consolidation cycles—allowing researchers to define sustained negativity with high precision. Interestingly, the 10⁻⁵ threshold was slightly more predictive than the deeper 10⁻⁶ threshold, likely due to fewer patients reaching that deeper level of remission in this dataset, though both thresholds remain important for clinical evaluation.
The study also highlights that MRD alone is not enough to guide therapy decisions. Patients with high-risk cytogenetic abnormalities (HRCAs) may still face a higher chance of relapse even if they achieve sustained MRD negativity, emphasizing the need to consider both disease biology and MRD results when planning treatment. Conversely, patients without high-risk features who reach S-MRD <10⁻⁵ may be candidates for safely reducing or pausing therapy.
Overall, Giri et al reinforce the value of MRD as a powerful tool for personalizing myeloma care, but one that should be used alongside traditional risk factors and clinical judgment. Their findings support continued research to refine MRD-based strategies and integrate them into risk-adapted treatment plans to maximize patient outcomes.
"Proteomic Analysis of Bone Marrow CD138+ Cells to Identify Proteins Associated With the Response of Multiple Myeloma Patients to Commonly Used Therapeutic Regimens"
Source
Paradeisi, F., Tserga, A., Lygirou, V., Makridakis, M., Stroggilos, R., Georgiou, G., Spyrou, G.M., Kostopoulos, I.V., Liacos, C.-I., Termentzi, A., Dimopoulos, M.A., Tsitsilonis, O., Vlahou, A., Kastritis, E. and Zoidakis, J. (2025), Proteomic Analysis of Bone Marrow CD138+ Cells to Identify Proteins Associated With the Response of Multiple Myeloma Patients to Commonly Used Therapeutic Regimens. Proteomics e70025. https://doi.org/10.1002/pmic.70025 August 7, 2025.
Overview
Researchers are working to better understand why multiple myeloma treatments sometimes fail. In this study, scientists analyzed bone marrow samples from patients who either responded well to their first therapy or did not respond. Using advanced proteomic testing, they identified over 1,100 proteins, with 230 showing clear differences between responders and non-responders. Many of these proteins were tied to the immune system and how cells regulate protein production—processes known to play a role in myeloma growth and treatment resistance.
The team confirmed their findings by comparing them to RNA data, which supported the link between certain proteins and treatment outcomes. Some of the proteins were already associated with myeloma, while others were newly discovered in this context. These results suggest that changes in immune activity and protein regulation may strongly influence how patients respond to therapy. In the future, this type of research could help doctors predict treatment response more accurately and guide the development of new therapies for multiple myeloma.
"Consensus Guidelines and Recommendations for the anti-CD38-based Therapy in Clinical Practice for Relapsed/Refractory Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group."
Source
Chen W, Cai Z, Chim CS, Chng WJ, Du J, Fu C, Gao W, Hanamura I, Hou J, Huang JS, Ishida T, Li C, Liu A, Ptushkin V, Takezako N, Wong RSM, Yoon DH. Consensus Guidelines and Recommendations for the anti-CD38-based Therapy in Clinical Practice for Relapsed/Refractory Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group. Clin Hematol Int. 2025 Aug 8;7(3):36-59. doi: 10.46989/001c.141401.
Overview
Anti-CD38 monoclonal antibodies, such as daratumumab and isatuximab, have become central to treating relapsed or refractory multiple myeloma. An expert panel recently reviewed the best ways to use these therapies, offering guidance on choosing treatment regimens, managing side effects, and tailoring care for elderly or frail patients. They highlighted that anti-CD38-based treatments work well across many patient groups, including those with high-risk features like 1q21+ cytogenetics. While resistance remains a challenge, the experts noted that re-treatment may still be an option after a break of 6 to 12 months, which can allow the immune system and CD38 expression to recover.
The consensus also stressed that anti-CD38 therapies can be effective and safe in older or more fragile patients if supported by careful monitoring. Looking forward, these antibodies are expected to play an even bigger role as they are combined with new immunotherapies such as CAR-T cells and bispecific antibodies. Overall, this guidance helps physicians make more personalized decisions for patients while underscoring the importance of continued research to strengthen and expand the role of anti-CD38 antibodies in multiple myeloma treatment.
"Redefining multiple myeloma treatment: Advances, challenges, and future directions in immunotherapy"
Source
Fu, Chengcheng1,2; Zhai, Yingying1,2; Yan, Lingzhi1,2; Jin, Song1,2; Shang, Jingjing1,2; Shi, Xiaolan1,2; Wu, Depei1,2. Redefining multiple myeloma treatment: Advances, challenges, and future directions in immunotherapy. Chinese Medical Journal ():10.1097/CM9.0000000000003655, August 08, 2025. | DOI: 10.1097/CM9.0000000000003655
Overview
Multiple myeloma continues to present major challenges because of its complexity and tendency to relapse, even with the many treatment advances of the past 20 years. Traditional therapies have helped extend survival, but the disease remains incurable for most patients, with treatment resistance still a significant hurdle. This review highlights the importance of treatment goals such as achieving and maintaining minimal residual disease negativity and supporting a balanced immune system to improve long-term outcomes.
Immunotherapy is reshaping the treatment landscape, especially for patients with relapsed or refractory disease. New approaches like CAR T-cell therapy, bispecific antibodies, and bispecific T-cell engagers are showing strong potential by directly targeting myeloma cells and disrupting the supportive bone marrow environment that helps the disease persist. Looking ahead, research is focusing on bringing immunotherapies into earlier stages of treatment and developing biomarkers to better match therapies to individual patients. These efforts aim to move the field closer to more personalized and durable treatment strategies for multiple myeloma.
"Real-World Experience with Teclistamab for Relapsed/Refractory Multiple Myeloma from the US Myeloma Immunotherapy Consortium"
Source
Beatrice M. Razzo, Shonali Midha, Andrew J. Portuguese, Ariel F. Grajales-Cruz, Andre De Menezes Silva Corraes, Patrick Costello, Yuxin Liu, Adam S. Sperling, Omar Nadeem, Danai Dima, Rahul Banerjee, Andrew J. Cowan, Aimaz Afrough, Larry D. Anderson, Alex Lieberman-Cribbin, Gurbakhash Kaur, Anmol Goyal, Shebli Atrash, Christopher J. Ferreri, Peter M. Voorhees, Oren Pasvolsky, Hans C. Lee, Krina K. Patel, Kelley L. Julian, Peter A. Forsberg, Megan M. Herr, Saurabh Chhabra, Ricardo D. Parrondo, Yi Lin, Anna Chen, Sandra P. Susanibar-Adaniya, Jack Khouri, Shahzad Raza, Faiz Anwer, Mariola Vazquez-Martinez, Omar Castaneda Puglianini, Douglas W. Sborov, James A. Davis, Adriana Rossi, Leyla Shune, Jenny Bhurtel, Wei-Ting Hwang, Doris K. Hansen, Surbhi Sidana, Alfred L. Garfall, Shambavi Richard; Real-World Experience with Teclistamab for Relapsed/Refractory Multiple Myeloma from the US Myeloma Immunotherapy Consortium. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-24-0354 August 8, 2025.
Overview
Tecvayli® (teclistamab), a bispecific antibody targeting CD3 and BCMA, is now approved for relapsed or refractory multiple myeloma, but real-world data provide a broader view of its use outside clinical trials. In a large U.S. study of more than 500 patients, nearly 90% would not have qualified for the pivotal MajesTEC-1 trial, often because of prior BCMA therapy, low blood counts, or poorer overall health. Despite this, the treatment showed meaningful activity, with over half of patients achieving at least a partial response and nearly half reaching a very good partial response or better.
Side effects were generally manageable, with cytokine release syndrome occurring in just over half of patients—though severe cases were rare—and neurotoxicity reported in about 1 in 10 patients. Infections were common and caused death in a small proportion of patients, highlighting the need for careful monitoring. After a median follow-up of about 10 months, median progression-free survival was just under 6 months, and the one-year overall survival rate was 61%. Patients who had recent BCMA CAR T-cell therapy, higher disease burden, or certain blood abnormalities tended to respond less well. These findings show that teclistamab remains an important option for heavily pretreated patients, though outcomes can vary depending on prior therapies and disease characteristics.
"SWIFT-seq enables comprehensive single-cell transcriptomic profiling of circulating tumor cells in multiple myeloma and its precursors"
Source
Lightbody, E.D., Sklavenitis-Pistofidis, R., Wu, T. et al. SWIFT-seq enables comprehensive single-cell transcriptomic profiling of circulating tumor cells in multiple myeloma and its precursors. Nat Cancer (2025). https://doi.org/10.1038/s43018-025-01006-0 August 8, 2025.
Overview
Researchers are working to make it easier to track and understand multiple myeloma without relying only on bone marrow biopsies, which can be invasive and sometimes inconclusive. In this study, they developed a new single-cell sequencing method called SWIFT-seq to analyze circulating tumor cells (CTCs) found in the blood of patients with myeloma and its precursor conditions. By comparing CTCs with bone marrow samples from more than 100 patients and healthy donors, the team was able to create a sequencing-based approach to count tumor cells and identify key genetic abnormalities.
Using this method, they also measured how quickly tumor cells were dividing and showed that CTCs can reveal important information about how the disease evolves over time. The researchers proposed a model suggesting that tumor burden, cell growth, genetic features, and a tumor’s ability to circulate all influence the number of CTCs in the blood. Overall, SWIFT-seq may make it possible to use a simple blood test to monitor myeloma progression, guide treatment decisions, and uncover new insights into how the disease spreads.
"Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple myeloma risk"
Source
Li, J., Li, Y., Wang, J. et al. Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple myeloma risk. Sci Rep 15, 29016 (2025). https://doi.org/10.1038/s41598-025-12804-y August 8, 2025.
Overview
New research suggests that omega-3 fatty acids may help reduce the risk of developing multiple myeloma (MM). Using a method called Mendelian randomization, researchers analyzed genetic data to explore whether higher omega-3 levels directly lower MM risk, and whether certain blood lipids play a role in this effect. Across multiple datasets, they found that omega-3 was associated with a roughly 20% lower risk of MM, even after accounting for other risk factors like obesity and type 2 diabetes.
The study also identified a specific lipid, phosphatidylcholine (18:2_20:4), that may help mediate this protective effect. This suggests that omega-3 might influence MM risk by affecting lipid metabolism in the blood. While more research is needed, these findings point to a potential role for omega-3 in MM prevention and may provide new insights into strategies for reducing the risk of this challenging blood cancer.
"Symptomatic progression-free survival as an emerging patient-centered endpoint in multiple myeloma: a secondary analysis of MagnetisMM-3 trial data"
Source
Kortüm, M., Theurich, S., Farrell, J. et al. Symptomatic progression-free survival as an emerging patient-centered endpoint in multiple myeloma: a secondary analysis of MagnetisMM-3 trial data. BMC Cancer 25, 1288 (2025). https://doi.org/10.1186/s12885-025-14724-6 August 8, 2025
Overview
Researchers are exploring new ways to measure treatment success in multiple myeloma (MM) that go beyond traditional markers like disease progression. A recent study introduced a patient-centered endpoint called symptomatic progression-free survival (SPFS), which combines standard progression-free survival (PFS) with patient-reported outcomes (PROs) such as pain, fatigue, and mobility. This approach aims to better reflect how patients actually feel and function during treatment.
Using data from the MagnetisMM-3 trial of elranatamab, investigators found that worsening of pain, fatigue, or poor mobility was strongly linked to a higher risk of disease progression or death. For example, a 10-point worsening in these symptoms corresponded to a 20–31% increased risk of progression. By combining symptom changes with traditional PFS, SPFS provides a more comprehensive and patient-focused measure of treatment impact. This new endpoint could help clinicians better understand and address the real-world experience of people living with MM.
"Real-world comparison of treatment outcomes for multiple myeloma in elderly transplant ineligible patients receiving first-line VRd, Rd and VCd: Results from the Australian and New Zealand Myeloma and Related Diseases Registry"
Source
Sarah Zhao, Cameron Wellard, Elizabeth M Moore, Andrew Spencer, Hang Quach, P. Joy Ho, Emma-Jane McDonald, Peter Mollee, Simon J Harrison, Bradley Augustson, Erica M Wood, Zoe K McQuilten, Rajeev Rajagopal, Real-world comparison of treatment outcomes for multiple myeloma in elderly transplant ineligible patients receiving first-line VRd, Rd and VCd: Results from the Australian and New Zealand Myeloma and Related Diseases Registry, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.08.004. August 9, 2025.
Overview
A recent real-world study examined treatment outcomes in elderly patients with newly diagnosed multiple myeloma who were not eligible for transplant. Using data from the ANZ Myeloma and Related Diseases Registry, researchers looked at 1,092 patients over age 70 treated between 2013 and 2024. The study compared three common regimens: bortezomib-cyclophosphamide-dexamethasone (VCd), lenalidomide-dexamethasone (Rd), and lenalidomide-bortezomib-dexamethasone (VRd).
Overall response rates were highest with VRd at 91.5%, followed by VCd at 85.6% and Rd at 73.7%. Median progression-free survival (PFS) was longest for VRd at 27.5 months, compared with 23.7 months for Rd and 20.5 months for VCd. After adjusting for patient factors, VRd and Rd both showed superior PFS compared with VCd. Interestingly, Rd patients experienced the longest time before needing their next treatment at 35.1 months, compared to 28.7 months for VRd and 20.1 months for VCd. Three-year overall survival (OS) was highest with VRd at 80%, while Rd and VCd were both at 67%, although statistical analysis did not show a significant OS difference.
These findings suggest that VRd provides the best disease control for older, transplant-ineligible patients in terms of PFS, while Rd offers a longer treatment-free interval. The study highlights the value of real-world evidence in guiding treatment decisions for elderly myeloma patients.
"A differential diagnostic model based on immunological evaluation and routine laboratory tests: distinguishing multiple myeloma from other disorders with aberrant immunoglobulin elevation"
Source
Li, M., Jia, S., Wu, H. et al. A differential diagnostic model based on immunological evaluation and routine laboratory tests: distinguishing multiple myeloma from other disorders with aberrant immunoglobulin elevation. Discov Onc 16, 1514 (2025). https://doi.org/10.1007/s12672-025-03156-0 August 9, 2025.
Overview
Researchers have developed a new diagnostic model to help doctors identify multiple myeloma (MM) early and reduce the risk of misdiagnosis. The model uses common blood and immune system tests, including immunoglobulin M (IgM), kidney function (glomerular filtration rate), high-density lipoprotein, red blood cell distribution, and thrombin time. Data were collected from 274 newly diagnosed MM patients and 137 patients with connective tissue diseases at Zhejiang Provincial People’s Hospital between 2008 and 2023.
The team divided the patients into training and validation groups to build and test the model. Using statistical analysis, they created a multivariate logistic regression model that could distinguish MM patients from others with similar lab abnormalities. The model performed exceptionally well, showing high accuracy, sensitivity, and specificity, with an area under the curve (AUC) of 0.980 in the training set and 0.954 in the validation set.
These results suggest that this model could be a powerful tool in clinical practice, helping doctors quickly and accurately differentiate MM from other conditions with similar lab findings. By streamlining early diagnosis, it may improve patient care and ensure timely treatment for those with multiple myeloma.
"Predicting survival of persons with newly-diagnosed multiple myeloma"
Source
Zhang, L., Wang, Y., Gale, R. et al. Predicting survival of persons with newly-diagnosed multiple myeloma. Cancer Cell Int 25, 301 (2025). https://doi.org/10.1186/s12935-025-03916-6 August 9, 2025.
Overview
Researchers have developed a new tool to better predict survival in patients with newly diagnosed multiple myeloma (NDMM), addressing limitations in existing systems like mSMART3.0. They analyzed clinical and laboratory data from 1,008 patients, dividing them into a training group and a validation group. Using statistical methods, they identified eight key factors that independently affect survival and built a baseline model to estimate 5-year outcomes.
The model performed well, with high accuracy in both the training and validation groups. In the training set, patients classified as high-risk had a 5-year survival of 34%, compared with 72% for those in the low-risk group, with similar results seen in the validation set. By combining the new model with mSMART3.0 data, the researchers improved its predictive power, raising the 5-year survival accuracy significantly compared to mSMART3.0 alone and outperforming other multiple myeloma staging systems.
These findings suggest that the new nomogram can provide more precise survival predictions for NDMM patients, helping doctors make better-informed treatment decisions and offering patients a clearer understanding of their prognosis.
"Implementing Video-Based Education for Multiple Myeloma Patients Preparing for Autologous Stem Cell Transplant: A RE-AIM Evaluation"
Source
Halpin, S.N., Konomos, M. Implementing Video-Based Education for Multiple Myeloma Patients Preparing for Autologous Stem Cell Transplant: A RE-AIM Evaluation. J Canc Educ (2025). https://doi.org/10.1007/s13187-025-02692-1 August 10, 2025.
Overview
Many patients with multiple myeloma (MM) face significant challenges when preparing for autologous stem cell transplant (ASCT), a complex procedure that requires careful self-management. Patients often feel overwhelmed, especially when learning how to care for central lines or administer subcutaneous injections. To help, researchers implemented a video-based education program called Ready for Transplant (R4T) alongside standard nurse-led education.
Over an 18-month study and follow-up period, the program was evaluated using observations of 152 clinical encounters and interviews with 35 patients and 7 clinicians. The findings showed that nurses adopted the videos into routine practice, and patients who watched them were more likely to successfully proceed to transplant. Nurses also adjusted their in-person teaching based on how patients interacted with the videos. The program proved especially helpful for older patients and caregivers, who could access the information repeatedly at their own pace.
R4T remained valuable even during the early COVID-19 pandemic, when remote education became essential. This study demonstrates that patient-centered, flexible education programs like video supplements can improve both patient preparedness and the effectiveness of clinician-led teaching in transplant settings.
"Real-World Outcomes of Multiple Myeloma in a Resource-Constrained Setting: A 14-Year Experience from a Tertiary Cancer Center in Jordan"
Source
Abeer Yaseen, Mohammad Ma'koseh, Albatol Alamoush, Anas Zayed, Mona Ribie, Marah Alzubi, Jawad Alrawabdeh, Teeba Mubaydeen, Rozan Alfar, Waleed Da'Na, Salwa Saadeh, Yazan Talab, Maysa Al-Hussaini, Husam Abu Jazar, Kamal Al-Rabi, Akram Al-Ibraheem, Samer Al Hadidi, Sameer Yaser, Zaid H. Abdel Rahman; Real-World Outcomes of Multiple Myeloma in a Resource-Constrained Setting: A 14-Year Experience from a Tertiary Cancer Center in Jordan. Blood Global Hematology 2025; 100024. doi: https://doi.org/10.1016/j.bglo.2025.100024 August 11, 2025.
Overview
At King Hussein Cancer Center in Jordan, researchers evaluated outcomes for adults with newly diagnosed multiple myeloma (NDMM) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) after first-line therapy between 2009 and 2023. The study included 221 patients, with a median age of 54 years. Most patients received a frontline regimen of bortezomib, thalidomide, and dexamethasone, while only a small fraction received lenalidomide. Response rates to initial therapy were high, with 2% achieving stringent complete response, 13% complete response, and 50% very good partial response.
After auto-HSCT, the depth of response improved significantly. Stringent complete responses rose to 13% and complete responses to 35%, demonstrating the transplant’s ability to deepen treatment outcomes. With a median follow-up of 48 months, median progression-free survival was 41.1 months, and overall survival reached 92 months.
These results highlight that auto-HSCT can meaningfully improve outcomes for NDMM patients, even in settings with limited access to newer therapies. However, the study also underscores the ongoing need for broader access to maintenance treatments and novel agents to further optimize care for patients in resource-limited environments.
"Efficacy of intensive antiemetic therapy including olanzapine in multiple myeloma patients treated with high-dose melphalan with autologous stem cell transplantation"
Source
Kato, J., Uchida, M., Ishikawa, M. et al. Efficacy of intensive antiemetic therapy including olanzapine in multiple myeloma patients treated with high-dose melphalan with autologous stem cell transplantation. Support Care Cancer 33, 777 (2025). https://doi.org/10.1007/s00520-025-09839-2 August 11, 2025.
Overview
A recent study evaluated how well an intensive four-drug anti-nausea regimen works for multiple myeloma patients receiving high-dose melphalan followed by autologous stem cell transplantation (ASCT). Researchers compared a standard antiemetic approach—using palonosetron, dexamethasone, and aprepitant—with an intensive regimen that added olanzapine for five days. The goal was to see which approach better prevented delayed chemotherapy-induced nausea and vomiting (CINV), occurring between days 2 and 5 after treatment.
The study included 122 patients, with 68 receiving the intensive regimen and 54 receiving standard care. Both groups were similar in baseline characteristics. Results showed that the intensive regimen significantly improved outcomes, with 52.9% of patients achieving a complete response—meaning no vomiting and no need for rescue medication—compared to 31.4% in the standard group. The intensive regimen also reduced the rate of severe nausea in the delayed phase, lowering it from 75.9% to 44.1%.
These findings suggest that adding olanzapine to the antiemetic regimen can safely enhance protection against delayed nausea and vomiting in multiple myeloma patients undergoing melphalan-based ASCT, helping improve patient comfort and treatment experience.
"Comparison of isatuximab-pomalidomide-dexamethasone versus elotuzumab-pomalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: a target trial emulation using real-world data"
Source
Martino EA, Pitino A, Offidani M, Pepa RD, Gozzetti A, Bongarzoni V, Maroccia A, Amico V, Stefanoni P, Zamagni E, Terlizzi S, Derudas D, Palmieri S, Bianco R, Conticello C, Brunori M, Rago A, Lotti F, Fontana R, Sgherza N, Rossi E, Cafro AM, Febbo MA, Quinto AM, Cerchione C, Casaluci GM, Citro A, Califano C, Zambello R, Mangiacavalli S, Liberatore C, Buda G, De Magistris C, Amendola A, Vigna E, Bruzzese A, Barbieri E, Quaresima M, Roccotelli D, Farina F, Micozzi J, Vincelli ID, Tarantini G, Antonioli E, Aquino S, Maggi A, Lombardo A, Bertuglia G, Furlan A, Mele A, Annibali O, Cotzia E, Benvenuti P, De Paoli L, Barilà G, Morè S, De Stefano V, Di Raimondo F, Petrucci MT, Bolli N, Musto P, Neri A, Morabito F, Tripepi G, Gentile M. Comparison of isatuximab-pomalidomide-dexamethasone <i>versus</i> elotuzumab-pomalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: a target trial emulation using real-world data. Haematologica 2025;110(8):1875-1881; https://doi.org/10.3324/haematol.2025.287325. August 2025.
Overview
A recent real-world study compared two triplet regimens for patients with relapsed or refractory multiple myeloma (RRMM) who had received at least two prior therapies: isatuximab, pomalidomide, and dexamethasone (IsaPd) and elotuzumab, pomalidomide, and dexamethasone (EloPd). Both regimens have shown efficacy and safety in clinical trials, but direct comparisons in real-world populations were lacking. Researchers combined two large real-world cohorts and used a target trial emulation (TTE) approach to reduce bias and better mimic randomized trial conditions. This method allowed for more accurate comparisons by balancing patient characteristics such as age, disease stage, cytogenetic risk, and prior treatment exposure.
The analysis included 277 patients with a median age of 70 years. Before adjustment, IsaPd appeared to produce higher response rates and longer progression-free survival (PFS) and overall survival (OS) than EloPd. However, after balancing for baseline differences using TTE, the differences between the two regimens were no longer statistically significant. Independent factors that predicted poorer outcomes included higher International Staging System (ISS) stage, high-risk cytogenetics, and prior exposure or refractoriness to daratumumab. Importantly, IsaPd maintained consistent effectiveness regardless of prior daratumumab exposure, alleviating concerns about potential cross-resistance between these CD38-targeting therapies.
Safety profiles differed between the regimens. IsaPd was linked to higher rates of grade 3–4 neutropenia and infections, whereas EloPd generally had lower hematologic toxicity. Gastrointestinal side effects and fatigue were similar between the two groups, and treatment discontinuation due to adverse events was rare for both. These findings highlight the importance of individualized treatment decisions, taking into account patient-specific risk factors, disease characteristics, and toxicity profiles. Both IsaPd and EloPd can serve as effective third-line options, potentially bridging patients to later therapies such as CAR-T cells or bispecific antibodies, while daratumumab refractoriness remains an important predictor of outcomes and an unmet clinical need.
"Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial"
Source
María-Victoria Mateos, Bruno Paiva, M Teresa Cedena, Noemí Puig, Ana Maria Sureda-Balari, Verónica Gonzalez de la Calle, Albert Oriol, Enrique M Ocio, Laura Rosiñol, Yolanda González Montes, Joan Bargay, María Esther González García, Sunil Lakhwani, Angel Ramirez Payer, Alexia Suarez-Cabrera, María-Jesús Blanchard, Sebastián Garzón, Felipe Casado Montero, Valentín Cabañas, Jaime Pérez de Oteyza, Mercedes Gironella, Joaquín Martinez-Lopez, Ana Isabel Teruel Casasús, María Pilar Delgado-Beltrán, Elena Prieto, Juan José Lahuerta, Joan Bladé, Jesús San-Miguel, Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial, The Lancet Haematology, Volume 12, Issue 8, 2025,Pages e588-e598, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00143-7. August 2025.
Overview
A recent phase 3 trial in Spain explored treatment options for transplant-ineligible patients with newly diagnosed multiple myeloma, focusing on frailty-based therapy adaptation. Patients aged 65–80 were assessed for frailty using the Geriatric Assessment in Hematology (GAH) scale and randomly assigned to one of three induction regimens. These included a standard VMP-Rd regimen combining Velcade® (bortezomib), melphalan, prednisone, Revlimid® (lenalidomide), and dexamethasone, a Kyprolis©- (carfilzomib) based triplet (KRd), or a quadruplet regimen adding daratumumab to KRd (D-KRd). Treatments were given in structured cycles, with dosing tailored over the course of therapy to optimize efficacy and manage toxicity in this older, frail population.
Patients who completed induction and consolidation therapy were then assessed for measurable residual disease (MRD). Those with either detectable or undetectable MRD were randomly assigned to maintenance therapy with daratumumab plus lenalidomide or no maintenance. The primary goal of the trial was to determine MRD negativity after induction, providing an early measure of deep treatment response. By incorporating frailty assessments and advanced regimens, the study aims to clarify how best to balance effectiveness and tolerability for older patients who cannot undergo transplant, offering insights into tailoring MM therapy in real-world, high-risk populations.
"Carfilzomib–lenalidomide–dexamethasone versus lenalidomide–dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial"
Source
Sara Bringhen, Lorenzo Cani, Elisabetta Antonioli, Daniele Derudas, Francesca Fazio, Alessandra Larocca, Sonia Ronconi, Claudia Cellini, Antonietta Pia Falcone, Fabrizio Accardi, Anna Marina Liberati, Piero Galieni, Angelo Belotti, Anna Maria Cafro, Roberto Ria, Giulia Benevolo, Iolanda Donatella Vincelli, Donato Mannina, Flavia Lotti, Benedetto Bruno, Vincenzo Marasco, Rita Mazza, Patrizia Tosi, Elena Rivolti, Mario Boccadoro, Mattia D’Agostino, Carfilzomib–lenalidomide–dexamethasone versus lenalidomide–dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial, The Lancet Haematology, Volume 12, Issue 8, 2025, Pages e621-e634, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00162-0. August 2025.
Overview
A recent phase 3 trial in Italy explored whether adding the second-generation proteasome inhibitor carfilzomib to Revlimid® (lenalidomide)–dexamethasone could improve outcomes for patients with newly diagnosed, transplant-ineligible multiple myeloma. The trial enrolled patients considered fit or intermediate-fit based on frailty scoring and measured disease according to standard criteria. Patients were randomly assigned to receive either weekly carfilzomib plus lenalidomide–dexamethasone or lenalidomide–dexamethasone alone. The main goals were to assess measurable residual disease (MRD) negativity after two years and progression-free survival.
The study enrolled 82 patients before it was stopped early due to the introduction of daratumumab–lenalidomide–dexamethasone as the new standard first-line treatment in Italy. Despite the smaller sample, results were striking. In the carfilzomib group, 60% of patients achieved MRD negativity compared with none in the lenalidomide–dexamethasone group. Progression-free survival was also significantly longer with carfilzomib–lenalidomide–dexamethasone, with median survival not yet reached, versus about 21 months in the control group. The most common serious side effects with the carfilzomib combination were neutropenia, thrombocytopenia, diarrhea, cardiac events, infections, and high blood pressure, though these were generally manageable.
Overall, this study suggests that adding carfilzomib to lenalidomide–dexamethasone may provide a deeper response and longer progression-free survival for transplant-ineligible patients, with predictable and controllable toxicities. These findings highlight the potential of this regimen as an effective option for patients who cannot undergo stem cell transplantation.
"A new chapter in relapsed or refractory multiple myeloma"
Source
The Lancet Haematology, A new chapter in relapsed or refractory multiple myeloma, The Lancet Haematology, Volume 12, Issue 8, 2025, Page e561, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00205-4. August 2025.
Overview
Despite decades of research, multiple myeloma remains incurable, although recent advances have dramatically changed treatment options. Therapies such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, antibody–drug conjugates, and CAR T-cell therapies have improved outcomes, particularly with newer first-line quadruplet regimens. However, these treatments can be complex, and relapse remains common. Each relapse, especially in refractory disease, limits available options and highlights the need for more personalized and innovative therapies. Recent clinical research and regulatory approvals are starting to provide new hope for patients with relapsed or refractory multiple myeloma.
One example is the BELLINI trial, which tested venetoclax in combination with bortezomib and dexamethasone. Overall, the trial showed no survival benefit for venetoclax in the general study population, though post-hoc analyses suggested potential benefits for patients with the t(11;14) mutation or high BCL2 expression. These findings emphasize the importance of biomarker-driven studies to identify patients most likely to benefit from targeted therapies.
Promising results have also emerged from the DREAMM-7 trial, which compared belantamab mafodotin—an antibody–drug conjugate targeting BCMA—plus bortezomib and dexamethasone (BVd) with an established anti-CD38 triplet regimen. Updated results after nearly 40 months showed a survival benefit with BVd and stable quality-of-life scores for patients, even among those experiencing vision-related side effects. The trial highlighted fatigue and decreased appetite as the symptoms most impacting patient wellbeing. Regulatory decisions are ongoing, with approvals in the UK and pending evaluations from the FDA and EMA for belantamab mafodotin-based combinations.
Adding to these advances, the EMA authorized linvoseltamab, a BCMA-directed CD3 T-cell engager, and the FDA granted accelerated approval in July 2025 for patients with at least three prior therapies. In the LINKER-MM1 trial, linvoseltamab showed a 70% overall response rate, with nearly half achieving complete responses. While risks such as cytokine release syndrome and neurotoxicity exist, most events were mild and resolved quickly compared with other anti-BCMA bispecifics.
Together, these developments in targeted therapy and patient-reported outcomes are transforming multiple myeloma care. Still, the growing number of options creates challenges in selecting the best treatment sequence. Experts suggest that the field now needs to adopt genomic-based classifications, similar to lymphoma and acute myeloid leukemia, to enable truly personalized treatment strategies that match the right therapy to the right patient.
"A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients"
Source
E.A. Martino, G. Caridà, D. Lofaro, A. Bruzzese, C. Labanca, F. Mendicino, E. Lucia, V. Olivito, N. Puccio, A. Neri, N. Amodio, E. Vigna, F. Morabito, M. Gentile, A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients, ESMO Open, Volume 10, Issue 8, 2025, 105514, ISSN 2059-7029, https://doi.org/10.1016/j.esmoop.2025.105514. August 2025.
Overview
For patients with relapsed or refractory multiple myeloma (RRMM), especially those who have been exposed to or are resistant to Revlimid® (lenalidomide), choosing the most effective second-line therapy is increasingly important. A recent network meta-analysis reviewed eight clinical trials including nearly 4,000 patients to compare lenalidomide-free regimens. The main focus was progression-free survival, using robust statistical methods to determine which treatments provided the greatest benefit.
The analysis found that the combination of belantamab mafodotin, bortezomib, and dexamethasone (BVd) was the most effective option for patients at first relapse, regardless of whether they were lenalidomide-exposed or lenalidomide-refractory. BVd consistently outperformed other triplet regimens, including combinations with daratumumab, isatuximab, carfilzomib, and pomalidomide, in prolonging progression-free survival.
Looking ahead, emerging therapies such as CAR T-cell treatments and bispecific antibodies are poised to further transform care for RRMM. Trials like CARTITUDE-4 and MajesTEC-3 are investigating these agents earlier in treatment, particularly for patients resistant to lenalidomide and daratumumab. This analysis provides a clear, evidence-based ranking of lenalidomide-free options, highlighting BVd as a preferred second-line therapy, while emphasizing the need for future studies to optimize treatment sequencing and explore novel therapies in earlier stages of disease.
"The comparison of cyclophosphamide at different dose levels for stem cell mobilization in multiple myeloma"
Source
Karakus, Abdullah et al. The comparison of cyclophosphamide at different dose levels for stem cell mobilization in multiple myeloma. Transfusion and Apheresis Science, Volume 64, Issue 4, 1041. August 2025.
Overview
A recent multi-center study examined the effectiveness of two different doses of Cytoxan® (cyclophosphamide, or Cy) for stem cell mobilization in patients with multiple myeloma. Researchers analyzed 169 adult patients treated between 2018 and 2024, comparing those who received 2 g/m² of Cy to those who received 3 g/m². The study focused on key measures such as the number of CD34+ stem cells collected during apheresis, the number of apheresis sessions required, peak peripheral blood CD34+ levels, and rates of mobilization failure.
The results showed that the higher 3 g/m² dose produced a greater stem cell yield compared to the 2 g/m² dose. Despite this, both groups had similar rates of mobilization failure, and the number of apheresis sessions needed to collect adequate stem cells did not differ significantly. These findings suggest that while the higher dose of cyclophosphamide may increase the total number of stem cells collected, lower doses remain effective and do not lead to more failed mobilizations or longer collection times.
Overall, this study supports the use of 3 g/m² Cy for maximizing stem cell yield, but it also reassures clinicians that lower doses are a safe and practical option when needed.
"MYC alterations in multiple myeloma: Genetic insights and prognostic impact"
Source
Sara Cristóbal-Vargas, Myriam Cuadrado, Norma C Gutiérrez, MYC alterations in multiple myeloma: Genetic insights and prognostic impact, Neoplasia, Volume 66, 2025, 101177, ISSN 1476-5586, https://doi.org/10.1016/j.neo.2025.101177. August 2025.
Overview
Multiple myeloma is marked by a wide range of genetic changes, some that appear early in disease development and others that emerge later as the cancer progresses. Among these, alterations in the MYC oncogene have gained attention as a possible driver of progression from precursor conditions like MGUS and smoldering myeloma to full disease. MYC acts as a transcription factor that supports the growth and survival of malignant plasma cells, and it can become abnormally active through mechanisms such as translocations, amplifications, or overexpression. Despite its importance, the role of MYC in predicting patient outcomes remains unclear, partly because different testing methods can produce conflicting results.
Researchers have also shown that mouse models of myeloma driven by MYC most closely mirror the human disease, making them valuable tools for studying disease biology. Current evidence suggests that targeting MYC could be a promising treatment strategy, though it has not yet been fully integrated into standard care. This review highlights what is known about MYC changes in myeloma, how they are detected, their potential influence on prognosis, and the therapeutic approaches being explored to inhibit MYC in patients.
"Allergic disease and risk of multiple myeloma: A case-control study"
Source
Simon Cheah, Adrian J. Lowe, Nina Afshar, Julie K. Bassett, Fiona J. Bruinsma, Wendy Cozen, Simon J. Harrison, John L. Hopper, Harindra Jayasekara, H. Miles Prince, Claire M. Vajdic, Nicole Wong Doo, Graham G. Giles, Shyamali C. Dharmage, Roger L. Milne, Allergic disease and risk of multiple myeloma: A case-control study, Cancer Epidemiology, Volume 97, 2025, 102839, ISSN 1877-7821, https://doi.org/10.1016/j.canep.2025.102839. August 2025.
Overview
Researchers explored whether allergic conditions may play a role in the risk of developing multiple myeloma. In this large study, 782 patients with myeloma were compared with 733 siblings or spouses without the disease. The analysis looked at self-reported conditions like asthma, eczema, food allergies, and hay fever to see if there were any links to myeloma risk.
The findings suggest that people with a history of allergic diseases, especially eczema, may have a lower risk of developing myeloma. Those who had both eczema and food allergies showed an even stronger protective effect. No clear connections were found for asthma, hay fever, or food allergies alone. While these results point to a possible protective role of some allergic conditions, more research is needed to understand why this link exists and what it could mean for prevention or risk assessment in multiple myeloma.
"Peripheral blood CD4+CD25+ T lymphocytes and TGF-β predict the prognosis in relapsed/refractory multiple myeloma treated with daratumumab"
Source
Hanyue Xue, Fang Wei, Ruiyang Li, Peripheral blood CD4+CD25+ T lymphocytes and TGF-β predict the prognosis in relapsed/refractory multiple myeloma treated with daratumumab, Seminars in Oncology, Volume 52, Issue 4, 2025, 152373, ISSN 0093-7754, https://doi.org/10.1016/j.seminoncol.2025.152373. August 2025.
Overview
For patients with relapsed or refractory multiple myeloma (R/RMM), Darzalex® (daratumumab)-based regimens are an important part of treatment. While many patients benefit, some still experience rapid disease progression, and the factors that predict outcomes are not well understood. In this study, researchers measured levels of CD4+CD25+ T lymphocytes and transforming growth factor-β (TGF-β) in the blood of R/RMM patients before starting daratumumab therapy. They compared these levels to those in newly diagnosed patients and looked at how they related to survival.
The results showed that R/RMM patients had higher levels of both CD4+CD25+ T lymphocytes and TGF-β compared with newly diagnosed patients. Importantly, patients with higher levels of these markers, as well as elevated serum creatinine, had significantly shorter progression-free survival on daratumumab. These findings suggest that high CD4+CD25+ T lymphocytes, TGF-β, and creatinine levels may serve as indicators of poor prognosis in R/RMM. Identifying these markers before treatment could help guide prognosis and tailor therapy more effectively.
"Dysregulated immune proteins in plasma in the UK Biobank predict multiple myeloma 12 years before clinical diagnosis"
Source
Joshua Fieggen, Anshul Thakur, Christopher C. Butler, Karthik Ramasamy, Anjan Thakurta, David A. Clifton, Lei Clifton; Dysregulated immune proteins in plasma in the UK Biobank predict multiple myeloma 12 years before clinical diagnosis. Blood Adv 2025; 9 (15): 3766–3770. doi: https://doi.org/10.1182/bloodadvances.2025016120 August 12, 2025.
Overview
This letter discusses new research on how blood-based proteomic profiling might help identify people at risk of developing multiple myeloma years before diagnosis. Currently, myeloma is often diagnosed late, once complications like anemia, bone damage, or kidney failure appear. Because early diagnosis is critical, researchers explored whether proteins in the blood could reveal early biologic changes that precede disease. Using plasma proteomic data from over 54,000 healthy UK Biobank participants and long-term follow-up, the team applied machine learning to identify proteins most strongly linked with future myeloma.
They found that several immune-related proteins, including SLAM family receptors, BCMA, and APRIL/TACI signaling pathways, were among the strongest predictors. Interestingly, some proteins traditionally linked to myeloma activity, like APRIL and BAFF, showed protective associations when measured in healthy individuals, suggesting a more complex role in early immune dysregulation. The proteomic model significantly outperformed traditional clinical models based on age, sex, and hemoglobin, with predictive accuracy sustained for more than a decade before diagnosis. These results suggest that plasma may carry early biomarkers of myeloma risk, independent of MGUS status. The authors note that future work should focus on refining these models, understanding the biology of these proteins, and developing clinically viable tests that could enable earlier detection and risk stratification in myeloma.
"A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma"
Source
Taxiarchis Kourelis, Sikander Ailawadhi, Dan T. Vogl, Sarah E. Gibson, Meaghen E. Sharik, Megan T. Du, Tyler D. Ames, Christina Y. Yim, Johan Baeck, Matthew R. Price, Jose M. Jimeno, Marta Chesi, P. Leif Bergsagel; A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-2574 August 12, 2025.
Overview
PT-112 is a new type of small molecule therapy being studied for cancer, including relapsed or refractory multiple myeloma (RRMM). Unlike traditional treatments, it works by disrupting ribosome production and stressing cancer cell organelles, which leads to a form of cell death that stimulates the immune system, known as immunogenic cell death. Because PT-112 contains a pyrophosphate structure, researchers were especially interested in testing it in myeloma, as this could help concentrate the drug in bone, where the disease often develops.
In mouse models of myeloma, PT-112 showed high uptake in bone and other organs. It was active both as a single drug and when combined with other treatments, lowering disease markers and improving survival in these preclinical studies. These results suggested it might work through mechanisms different from existing myeloma therapies.
A Phase I clinical trial tested PT-112 in heavily pretreated patients with RRMM who had already exhausted available therapies. The drug was given at increasing doses, and researchers found it was safe, well tolerated, and established a recommended dose for future studies. Encouragingly, some patients showed confirmed responses and other signs of activity, suggesting PT-112 could offer benefit even after standard treatments no longer work.
These findings support continued development of PT-112 as a potential option for patients with RRMM, with Phase 2 trials now warranted to better understand its role in treatment.
"Proportional and functional anomalies of CD38+ NK Cells:A new mechanism for impaired anti-tumour immunity in multiple myeloma?"
Source
Huixian Chen, Kehua Fang, Jinbao Zong, Xiaotian Chang, Proportional and functional anomalies of CD38+ NK Cells:A new mechanism for impaired anti-tumour immunity in multiple myeloma?, Immunobiology, 2025, 153107, ISSN 0171-2985, https://doi.org/10.1016/j.imbio.2025.153107. August 12, 2025.
Overview
In multiple myeloma (MM), abnormal immune cell numbers and function contribute to weakened anti-tumor responses and disease progression. Natural killer (NK) cells that express CD38 play an important role in regulating the immune system, but their behavior in MM has not been fully understood.
Researchers compared peripheral blood samples from healthy volunteers and newly diagnosed MM (NDMM) patients, focusing on CD38+ NK cells and the subset that also expresses CD16. They also tested how these cells influenced myeloma cell growth and survival, as well as their impact on the development of regulatory T cells (Tregs), which can suppress immune activity.
The study found that NDMM patients had significantly fewer CD38+ NK cells and CD38+CD16+ NK cells than healthy individuals. When co-cultured with myeloma cells, CD38+ NK cells from NDMM patients slightly increased cancer cell death, but both NDMM and healthy NK cells similarly inhibited myeloma cell growth. Notably, CD38+ NK cells from NDMM patients promoted the differentiation of CD4+ T cells into Tregs more than NK cells from healthy volunteers.
These findings suggest that in multiple myeloma, both the number and function of CD38+ NK cells are altered, contributing to the immunosuppressive environment that allows the disease to grow and evade the immune system
"Frailty dynamics and their impact on QoL in patients undergoing autologous HCT for multiple myeloma: Results from a multicentre GETH-TC study"
Source
Tolosa-Ridao C, González MB, Gómez MA, Fox L, Pérez Artigas MdM, Santamaría A, et al. Frailty dynamics and their impact on QoL in patients undergoing autologous HCT for multiple myeloma: Results from a multicentre GETH-TC study. Br J Haematol. 2025; 00: 1–13. https://doi.org/10.1111/bjh.70068 August 12, 2025.
Overview
A recent multicenter study looked at how frailty affects adults with multiple myeloma (MM) who undergo autologous hematopoietic cell transplantation (auto-HCT). Researchers used the HCT Frailty Scale to assess 269 patients at three time points: the first consultation, transplant admission, and day +100. They also measured quality of life (QoL) using the EuroQol (EQ-5D-5L) questionnaire. At the first consultation, nearly 24% of patients were classified as fit, 58% as pre-frail, and 19% as frail. Frailty was linked to older age, more advanced disease, and lower performance status.
Frailty was not static: by the time of transplant admission, about one-third of patients had a change in their frailty status. Frail patients were more likely to be readmitted after transplant (14.7%) and reported significantly lower QoL compared with pre-frail or fit patients. While differences in non-relapsed mortality (NRM) were not statistically significant, frail and pre-frail patients had higher one-year NRM (4.8% and 3.4%, respectively) compared with fit patients, who had none. By day +100, 34% of patients were fit, 56% pre-frail, and 8% frail, with frail patients continuing to experience poorer QoL.
The study highlights the value of the HCT Frailty Scale for identifying and tracking frailty in MM patients undergoing auto-HCT. Because frailty can change over time, ongoing assessments are crucial to guide personalized care, minimize complications, and improve both outcomes and quality of life.
"Real-world effectiveness of immunoglobulin replacement for hypogammaglobulinemia and infections in multiple myeloma"
Source
Elizabeth O’Donnell, Thais Gift, Zaid Yousif, Nikhil Khandelwal, Raj Desai, Lynn Huynh, Louise Clear, Megan Pinaire, Mingchen Ye, Azeem Banatwala, Gregory Belsky, Yichuan Grace Hsieh, Christopher Herrick, Mei Sheng Duh, Shawn N. Murphy, Marie Sanchirico; Real-world effectiveness of immunoglobulin replacement for hypogammaglobulinemia and infections in multiple myeloma. Blood Adv 2025; 9 (15): 3780–3789. doi: https://doi.org/10.1182/bloodadvances.2024015477 August 12, 2025
Overview
A recent real-world study evaluated the effectiveness of immunoglobulin replacement therapy (IgRT) in patients with multiple myeloma (MM) who experience low immunoglobulin levels and frequent infections. Researchers analyzed data from 6,062 adults with MM, finding that 471 patients (about 8%) received at least one IgRT treatment. They compared infection rates and immunoglobulin G (IgG) levels before and after IgRT.
The results showed that infections decreased significantly within three months of starting IgRT, with patients having 29% lower odds of infection compared with before treatment. Among patients with available lab data, nearly two-thirds had low IgG levels (hypogammaglobulinemia) before treatment. After starting IgRT, significantly fewer patients had low IgG, indicating improved immune function.
These findings suggest that IgRT can effectively reduce both infections and hypogammaglobulinemia in patients with MM. While IgRT is already used in clinical practice, there is potential to optimize dosing and treatment schedules to further lower the risk of infections and improve patient outcomes.
"Retrospective cohort study on alkaline phosphatase and ICU mortality rate of multiple myeloma"
Source
Wang, Qh., Dong, Gx. & Cong, Hb. Retrospective cohort study on alkaline phosphatase and ICU mortality rate of multiple myeloma. Sci Rep 15, 29623 (2025). https://doi.org/10.1038/s41598-025-05458-3 August 13, 2025.
Overview
A recent study explored the role of alkaline phosphatase (ALP) levels in predicting outcomes for patients with multiple myeloma (MM) admitted to the intensive care unit (ICU). Unlike in other cancers, ALP in MM may carry unique clinical significance, but its relationship with ICU mortality had not been well studied. Researchers conducted a retrospective analysis of 161 MM patients from the Medical Information Mart for Intensive Care database, examining how ALP levels correlated with in-hospital mortality.
The study found a nonlinear relationship between ALP levels and ICU mortality. Patients with ALP levels around 50 IU/L had the lowest risk of death, while both lower and higher levels were associated with increased mortality. Specifically, ALP levels between 22–62 IU/L were linked to lower mortality compared with slightly higher levels. These findings suggest that ALP could serve as a useful marker for identifying MM patients at higher or lower risk during critical illness. While further research is needed, monitoring ALP may help guide clinical decisions and improve outcomes for MM patients in the ICU.
"Kaempferol Induces Mitophagy and Disrupts Iron Metabolism via SFXN2 Leading to Apoptosis in Multiple Myeloma Cells"
Source
Hao Wang, Jia Song, Yan Shi, Nanhao Meng, Yanran Luo, Fengping Peng, Fengjuan Jiang, Rong Fu, Zhaoyun Liu, Kaempferol Induces Mitophagy and Disrupts Iron Metabolism via SFXN2 Leading to Apoptosis in Multiple Myeloma Cells, Free Radical Biology and Medicine, 2025,ISSN 0891-5849, https://doi.org/10.1016/j.freeradbiomed.2025.08.020. August 13, 2025.
Overview
Recent research has explored the effects of kaempferol, a natural plant flavonoid, on multiple myeloma (MM) cells. The study found that kaempferol can slow the growth of MM cells and trigger their programmed cell death, or apoptosis, in a dose-dependent manner. This effect appears to be linked to damage in the mitochondria—the cell’s energy centers—and an increase in mitochondrial autophagy, a process that removes damaged mitochondria. Kaempferol also disrupted iron metabolism in the cells by reducing the expression of SFXN2, a protein involved in transporting iron into mitochondria, while causing intracellular iron levels to rise.
In mouse models of MM, kaempferol inhibited tumor growth and promoted apoptosis, with stronger effects observed when combined with iron. These findings suggest that kaempferol works by targeting the SFXN2 pathway, creating mitochondrial iron imbalance and enhancing mitochondrial self-clearance in MM cells. By regulating this kaempferol–SFXN2 axis, researchers believe a new therapeutic approach for multiple myeloma could be developed, potentially offering a novel way to complement existing treatments.
"Risk factors and clinical impact of cytomegalovirus DNAemia in patients with multiple myeloma treated with teclistamab"
Source
Charles Pei, Zeinab El Boghdadly, Lisa Blackburn, Nidhi Sharma, Naresh Bumma, Abdullah M. Khan, Srinivas Devarakonda, Elvira Umyarova, Don Benson, Ashley Rosko, Francesca Cottini; Risk factors and clinical impact of cytomegalovirus DNAemia in patients with multiple myeloma treated with teclistamab. Blood Neoplasia 2025; 2 (3): 100097. doi: https://doi.org/10.1016/j.bneo.2025.100097 August 20, 2025.
Overview
A recent study examined cytomegalovirus (CMV) reactivation in patients with relapsed or refractory multiple myeloma treated with teclistamab, a T-cell–redirecting bispecific antibody targeting BCMA. While teclistamab is effective, it can cause immune suppression, including low antibody levels and reduced lymphocytes, which may increase the risk of infections. The study followed 23 heavily pretreated patients and found that more than half (52%) developed CMV DNA in their blood during therapy, with symptoms ranging from fatigue and fever to blood count abnormalities. CMV syndrome, which combines CMV detection with systemic symptoms, occurred in 42% of these patients.
Interestingly, the presence of CMV DNAemia was not linked to lymphocyte counts early in treatment, suggesting that broader immune dysfunction, rather than simple low lymphocyte levels, may drive reactivation. Patients with CMV DNAemia also experienced more other infections, required antiviral therapy, and had fewer doses of teclistamab. Their response rates were lower, with complete responses achieved in only 33% compared with 73% in patients without CMV reactivation. This indicates that CMV reactivation may reflect wider immune exhaustion and may compromise both treatment effectiveness and infection control.
The study highlights the potential importance of monitoring for CMV during teclistamab therapy, even though current guidelines do not recommend routine screening. Despite limitations, including a small single-center cohort, the findings suggest that proactive antiviral management and careful immune monitoring may be critical to support patients, maintain treatment responses, and reduce the risk of serious infections during teclistamab therapy.
"CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNA"
Source
Eugenio Morelli, Anil Aktas-Samur, Domenico Maisano, Claire Gao, Vanessa Favasuli, Dimitrios Papaioannou, Giovanni De Nola, Jon E. Henninger, Na Liu, Marcello Turi, Pietro Folino, Laure Vreux, Michela Cumerlato, Liang Chen, Iannis Aifantis, Mariateresa Fulciniti, Kenneth C. Anderson, Abigail K. R. Lytton-Jean, Annamaria Gullà, Richard A. Young, Mehmet K. Samur, Nikhil C. Munshi; CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs. Blood 2025; 146 (7): 847–860. doi: https://doi.org/10.1182/blood.2025028746 August 14, 2025
Overview
A new study highlights the important role of long noncoding RNAs (lncRNAs) in multiple myeloma (MM), revealing that many of these molecules are essential for tumor growth. Using RNA-targeting CRISPR-Cas13d technology, researchers were able to identify and study hundreds of tumor-essential lncRNA (te-lncRNA) isoforms in MM cells. Some of these lncRNAs were specific to MM, while others were important across multiple cancer types, and their functions were further confirmed in animal models.
The study also explored where these lncRNAs are located within cells, identifying more than 30 cytosolic isoforms that were critical for tumor survival. One notable isoform of small nucleolar RNA host gene 6, found in the endoplasmic reticulum, interacts with heat shock proteins to help maintain protein balance within cells, a key process for myeloma cell survival. To support ongoing research, the team integrated their functional and clinical findings into the publicly available LongDEP Portal, offering a valuable resource for scientists studying lncRNAs. This work provides new insights into the molecular drivers of MM and highlights potential targets for future therapies.
"Linc-ing” RNA isoforms to function in multiple myeloma"
Source
Xabier Agirre, Felipe Prósper; “Linc-ing” RNA isoforms to function in multiple myeloma. Blood 2025; 146 (7): 773–774. doi: https://doi.org/10.1182/blood.2025029743 August 14, 2025.
Overview
A recent commentary in Blood highlights a study by Morelli and colleagues that sheds new light on the role of long noncoding RNAs (lncRNAs) in multiple myeloma (MM). LncRNAs are RNA molecules longer than 200 nucleotides that do not code for proteins but can regulate key cellular processes. While thousands of lncRNAs have been identified, the functions of most remain unknown, especially their distinct isoforms. Morelli et al used an innovative RNA-targeting CRISPR-Cas13d system to study 5,327 lncRNA isoforms in MM cells, allowing them to pinpoint which specific isoforms are essential for tumor survival. Unlike conventional Cas9-based approaches that target DNA, Cas13d directly cleaves RNA, making it ideal for studying lncRNAs that overlap with other genes or produce multiple isoforms.
Using this approach, the team identified 183 tumor-essential lncRNA isoforms in MM, with 86 of these also essential in other cancers. High expression of these isoforms correlated with their importance for tumor survival, suggesting that mechanisms such as epigenetic changes or activation of alternative promoters may drive their elevated levels in cancer cells. Importantly, the study found that high expression of 92 of these tumor-essential isoforms was linked to worse overall survival in MM patients, indicating that lncRNAs may have prognostic value and could help refine risk stratification.
The researchers also mapped where these lncRNA isoforms are located inside cells, finding most were chromatin-bound in the nucleus, though some, like the SNHG6-003 isoform, were predominantly cytoplasmic. This subcellular localization is critical for designing RNA-based therapies. For example, nuclear lncRNAs could be targeted with antisense oligonucleotides, while cytoplasmic lncRNAs might be addressed using small interfering RNAs. RNA-based therapies, inspired in part by mRNA vaccine technology, hold promise for cancer treatment, but challenges remain in improving stability, delivery, and tumor-specific targeting.
Overall, this work not only expands our understanding of lncRNA isoforms in MM but also provides a roadmap for developing precision RNA-targeted therapies. By linking specific isoforms to tumor survival and patient outcomes, it opens new possibilities for personalized treatments that could transform care for multiple myeloma and other cancers.
"Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax"
Source
Valentino, I., Gallo Cantafio, M.E., Torcasio, R. et al. Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax. J Transl Med 23, 917 (2025). https://doi.org/10.1186/s12967-025-06942-0 August 14, 2025.
Overview
A recent study explored how mitochondrial dynamics—specifically the balance between fission and fusion—affect multiple myeloma (MM) cell survival and drug response. Researchers focused on MARCH5, an E3 ubiquitin ligase that negatively regulates mitofusin 2 (MFN2), a key driver of mitochondrial fusion. In MM cell lines, reducing MARCH5 levels caused mitochondria to elongate and increased MFN2 expression, likely by preventing MARCH5 from tagging MFN2 for degradation. This shift toward mitochondrial fusion impaired energy production through oxidative phosphorylation, reduced ATP levels, and triggered apoptosis in the cancer cells.
The team found that similar effects could be achieved by directly increasing MFN2 activity, either genetically or using the drug leflunomide, both in cultured cells and in mouse models of MM. Analysis of gene expression in MARCH5-depleted cells revealed decreased activity in pathways involved in the mitochondrial electron transport chain and ATP synthesis, processes that are often linked to resistance to venetoclax, a targeted therapy for MM. Consistent with this, both MARCH5 knockdown and MFN2 activation made MM cells more sensitive to venetoclax.
These findings suggest that targeting the MARCH5–MFN2 pathway to promote mitochondrial fusion could be a promising strategy to weaken MM cells and improve responses to venetoclax. By disrupting the cancer cells’ energy production, this approach could help overcome drug resistance and offers a potential new avenue for therapy in MM patients.
"Eliminating the need for sequential confirmation of response in multiple myeloma"
Source
Jean-Sébastien Claveau, Prashant Kapoor, Moritz Binder, Francis Buadi, David Dingli, Angela Dispenzieri, Amie Fonder, Morie Gertz, Wilson Gonsalves, Suzanne Hayman, Miriam Hobbs, Yi Lisa Hwa Christenson, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert Kyle, S. Vincent Rajkumar, Shaji K. Kumar; Eliminating the need for sequential confirmation of response in multiple myeloma. Blood 2025; 146 (7): 802–805. doi: https://doi.org/10.1182/blood.2024027949 August 14, 2025.
Overview
A recent study evaluated a simpler way to confirm disease progression in multiple myeloma (MM) using measurements of monoclonal protein, such as serum and urine protein electrophoresis, serum free light chains, or quantitative immunoglobulins. Current guidelines from the International Myeloma Working Group recommend confirming progression with two sequential assessments of the same marker before starting a new therapy. However, this approach can be cumbersome, especially in clinical trials.
The researchers looked at 583 episodes of confirmed progression in MM patients enrolled in Mayo Clinic clinical trials. They found that nearly 70% of these episodes met progression criteria in two markers at the same time on the first test, suggesting that progression could be identified immediately. Furthermore, among 413 patients who met the criteria simultaneously, 98% went on to have confirmed progression by the standard sequential method.
These findings suggest that when two disease markers indicate progression at the same time, repeating a single marker for confirmation may not be necessary. This approach could streamline monitoring in clinical trials and routine care, making it faster and easier to identify when MM is advancing.
"Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR T cells"
Source
Corynn Kasap, Adila Izgutdina, Bonell Patiño-Escobar, Amrik S. Kang, Nikhil Chilakapati, Naomi Akagi, Ananya Manoj, Haley Johnson, Tasfia Rashid, Juwita Werner, Abhilash Barpanda, Huimin Geng, Yu-Hsiu T. Lin, Sham Rampersaud, Daniel Gil-Alós, Amin Sobh, Daphné Dupéré-Richer, Adolfo Aleman, Gianina Wicaksono, K. M. Kawehi Kelii, Radhika Dalal, Emilio Ramos, Anjanaa Vijayanarayanan, Kiran Lakhani, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, Ons Zakraoui, Isa Tariq, Ajai Chari, Alfred Chung, Anupama D. Kumar, Thomas G. Martin, Jeffrey Wolf, Sandy W. Wong, Veronica Steri, Mala Shanmugam, Lawrence H. Boise, Tanja Kortemme, Samir Parekh, Elliot Stieglitz, Jonathan D. Licht, William J. Karlon, Benjamin G. Barwick, Arun P. Wiita; Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR T cells. Blood 2025; 146 (7): 819–833. doi: https://doi.org/10.1182/blood.2024025536 August 14, 2025.
Overview
A new study highlights a potential strategy to improve outcomes for multiple myeloma (MM) patients with high-risk cytogenetic features, who often relapse quickly despite B-cell maturation antigen (BCMA)–targeted CAR T-cell therapy. Researchers identified CD70 as a cell surface protein that is specifically upregulated in high-risk myeloma tumors and may serve as an effective immunotherapy target. Using a structure-guided approach, they developed a CD27-based anti-CD70 CAR-T design that outperformed conventional single-chain variable fragment CARs, achieving more than an 80-fold increase in CAR-T expansion in animal models.
Further analysis using machine learning revealed the transcription factors and networks responsible for driving CD70 expression in high-risk myeloma. The study also explored dual-targeting CAR-Ts that attack both CD70 and BCMA, offering a promising strategy to prevent resistance caused by antigen escape. Overall, these findings suggest that optimized CD70-targeted CAR-T therapies could provide a new treatment option for high-risk MM patients and support further clinical development of this approach.
"CD70-CAR-Ts: a second wind for high-risk myeloma"
Source
Luis Gerardo Rodríguez-Lobato, Carlos Fernández de Larrea; CD70-CAR-Ts: a second wind for high-risk myeloma. Blood 2025; 146 (7): 769–771. doi: https://doi.org/10.1182/blood.2025029577 August 14, 2025.
Overview
In a recent commentary in Blood, Kasap and colleagues highlight an innovative CAR-T approach targeting CD70, offering new hope for patients with high-risk multiple myeloma (MM) who have relapsed after BCMA-directed therapies. While BCMA-targeted therapies have transformed MM treatment, patients with high-risk cytogenetic abnormalities—such as t(4;14), 1q gain, or del(17p)—often experience short-lived responses, with median progression-free survival of just 4 to 6 months after BCMA CAR-T. Relapse in these patients is driven by multiple factors, including genetic changes in tumor cells, T-cell exhaustion, and the suppressive bone marrow environment.
CD70 emerges as a promising target because it is preferentially expressed in high-risk MM subtypes, retained in BCMA-resistant cells, and largely absent in healthy blood-forming cells, suggesting a favorable safety profile. Its expression is regulated by epigenetic factors like NSD2 and TFAP2A, and can be increased by hypomethylating agents, pointing to potential combination strategies. To avoid CAR-T fratricide, CD70 must be knocked out in the T cells themselves.
The study’s CAR design is particularly noteworthy. Instead of a conventional antibody fragment, the CAR uses the natural ligand CD27 to bind CD70, resulting in 80- to 100-fold greater expansion in preclinical models without losing specificity. This structure-guided design may reduce immunogenicity and improve CAR-T function. To address antigen escape, the team also developed a bicistronic CAR targeting both CD70 and BCMA, which maintains efficacy even if one antigen is lost, offering a potential solution to resistance seen after single-antigen therapies.
While the preclinical results are compelling, the approach has limitations. Safety, persistence, and off-tumor effects remain untested in immunocompetent models, and gene editing adds manufacturing complexity. Clinically, questions remain about optimal dosing, durability of responses, and whether CD70 expression can reliably guide patient selection.
Overall, this work demonstrates the potential of precision CAR-T therapy using rational target selection and structure-guided design. For patients with high-risk, BCMA-refractory MM, CD70-targeted CAR-Ts may represent a promising next-generation immunotherapy that could expand treatment options and improve outcomes.
"Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma"
Source
Sebastian, T., Rajeeve, S., Farzana, T. et al. Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma. Blood Cancer J. 15, 137 (2025). https://doi.org/10.1038/s41408-025-01343-4 August 14, 2025.
Overview
A recent letter to the editor highlights real-world outcomes of BCMA-directed CAR T-cell therapy in patients with relapsed or refractory multiple myeloma (RRMM), focusing on the impact of prior Darzalex® (daratumumab) exposure. Patients with RRMM who have progressed after three or more lines of therapy, including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies, generally have a poor prognosis, with median overall survival under one year. With the approval of CAR T products ide-cel and cilta-cel for patients after only one to two prior therapies, questions remain about how prior daratumumab refractoriness affects outcomes.
In this single-center retrospective study, 171 patients treated with CAR T between 2018 and 2024 were analyzed, including 144 who were daratumumab-refractory and 27 who were non-refractory. The study found that while non-refractory patients were slightly less heavily pretreated and had lower rates of extramedullary disease (EMD), overall response rates were similar between groups, with 82% achieving at least a partial response. Median progression-free survival was 11 months for the entire cohort, with no statistically significant differences between refractory and non-refractory patients. Median overall survival was 34 months, again with comparable outcomes between groups.
Multivariate analysis identified factors associated with poorer outcomes, including use of CAR T products other than cilta-cel, prior BCMA-directed therapy, high-risk cytogenetics, EMD, and high disease burden. Side effects were consistent with prior reports of CAR T therapy, including cytokine release syndrome, neurotoxicity, infections, cytopenias, and hypogammaglobulinemia.
This study provides the first real-world evidence that daratumumab refractoriness may not significantly affect CAR T efficacy. The findings suggest that daratumumab-based therapies can be used for initial salvage in non-refractory patients, while CAR T therapy can be reserved for later lines without compromising outcomes. However, high-risk features such as EMD, cytogenetic abnormalities, prior BCMA exposure, and high disease burden remain important predictors of inferior response and survival. Despite limitations like its retrospective design and small non-refractory cohort, the study offers valuable insights for sequencing therapies in RRMM and supports ongoing evaluation of CAR T in earlier treatment lines.
"Global burden and trends of multiple myeloma attributable to high body mass index: a comprehensive analysis of the global burden of disease 2021 study with projections to 2040"
Source
Xie, Y., Li, J., Yu, J. et al. Global burden and trends of multiple myeloma attributable to high body mass index: a comprehensive analysis of the global burden of disease 2021 study with projections to 2040. BMC Public Health 25, 2774 (2025). https://doi.org/10.1186/s12889-025-24141-w August 14, 2025.
Overview
Obesity is becoming an increasingly important risk factor for both the development and progression of multiple myeloma. A new global analysis looked at how high body mass index (BMI) contributes to the burden of myeloma across different regions, ages, and socioeconomic groups. Using data from the Global Burden of Disease 2019 study, researchers found that deaths and disability linked to high BMI in myeloma have risen sharply over the past three decades. Between 1990 and 2021, myeloma deaths tied to high BMI more than tripled, while years of life lost to illness and disability also grew significantly.
The impact was greatest in wealthier regions like Western Europe and North America, though the fastest growth occurred in lower-income areas. Men consistently showed higher death and disability rates than women, and the oldest patients were the most affected. The study also found that the myeloma burden linked to high BMI strongly correlated with both socioeconomic development and obesity prevalence, suggesting that the problem will likely worsen without intervention. Projections show that deaths and disability will continue to rise through 2040. These findings highlight the urgent need for targeted prevention and public health strategies to address obesity as a modifiable risk factor for myeloma.
"Microbiota Shape Metabolic and Immune Determinants of CAR-T Therapy and Correlate with Outcomes in Myeloma"
Source
Mireia Uribe-Herranz, Aina Oliver-Caldés, Neus Martínez-Micaelo, Marta Español-Rego, Maria Val-Casals, Roberto Martínez-Soler, Elisa Rubio-Garcia, Valeria Brunello, Erik Z. Mihelic, Nela Klein-González, Daniel Benítez-Ribas, Núria Amigó, Andrea Vergara, Valentin Ortiz-Maldonado, Luis Gerardo Rodríguez-Lobato, Julio Delgado, Iñaki Ortiz de Landazuri, Verónica González-Calle, Valentín Cabañas, Beatriz Martin-Antonio, Lorena Pérez-Amill, Juan Luis Reguera-Ortega, Paula Rodríguez-Otero, Bruno Paiva, Joaquín Martínez-López, Maria-Victoria Mateos, Mariona Pascal, Álvaro Urbano-Ispizua, Europa Azucena González-Navarro, Carlos Fernández de Larrea, Manel Juan; Microbiota Shape Metabolic and Immune Determinants of CAR-T Therapy and Correlate with Outcomes in Myeloma. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-24-0203.
Overview
Researchers are beginning to uncover how the gut microbiome and its metabolites may influence the success of CAR T-cell therapy in multiple myeloma. In this study, patients treated with the BCMA-directed CAR-T therapy ARI0002h showed links between stool metabolites—especially succinate—and CAR T-cell persistence. Laboratory work confirmed that succinate boosted the survival and function of CAR T cells, helping them maintain a “central memory” profile that supports longer-lasting activity. In a mouse model of myeloma, a succinate-rich diet also improved CAR T-cell persistence and hinted at better tumor control.
The study further identified certain gut bacteria, including Acidaminococcaceae, Monoglobaceae, and Akkermansiaceae, that were tied to CAR T-cell outcomes. By combining bacterial and metabolite data, researchers created models that could predict which patients were more likely to achieve complete responses at 100 and 180 days after infusion. These findings suggest that the microbiome could serve as a powerful tool for assessing treatment response and guiding strategies to enhance CAR T-cell therapy in multiple myeloma.
"Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma"
Source
Kegyes, D., Bancos, A., Tigu, A.B. et al. Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma. Biomark Res 13, 105 (2025). https://doi.org/10.1186/s40364-025-00825-8 August 15, 2025.
Overview
Multiple myeloma (MM) is a blood cancer that continues to challenge researchers and doctors despite major progress in treatment. According to this source, in 2022, there were more than 118,000 new cases and 121,000 deaths worldwide. Over the years, treatment has shifted from standard chemotherapy to more targeted therapies designed to address the disease’s complexity. Because MM cells often develop resistance to single drugs, combination strategies that attack multiple disease pathways at once have become essential. A key part of this progress is the development of CELMoDs—new drugs such as iberdomide (CC-220) and mezigdomide (CC-92480)—which are more powerful versions of earlier immunomodulatory agents. CELMoDs bind 10 to 20 times more strongly and drive faster, deeper breakdown of proteins like Ikaros and Aiolos that fuel myeloma growth.
While survival rates have improved, with fit patients living more than 10 years on average and U.S. 5-year survival approaching 60%, MM remains incurable, and most patients eventually relapse. Researchers are now studying how CELMoDs can be combined with immunotherapies, including CAR T-cell and bispecific antibody treatments, to deepen and extend responses. Early evidence shows that these combinations improve outcomes and may serve as an effective bridge to transplant or as maintenance after stem cell transplant. Taken together, the findings highlight how CELMoDs may help reshape the next generation of multiple myeloma therapy by enhancing the durability and power of cellular and immune-based approaches.
"Cinobufagin overcomes bortezomib resistance in multiple myeloma strains by targeting SEC62/TRPM4-mediated NECSO"
Source
Zhao Yin, Guangchao Lil, Qi Zhong, Xiaoting Zhang, Ruiming Ou, Huijuan Shen, Jing Huang, Shaya Mahati, Zhi Liu, Yangmin Zhu, Qing Zhang, Shuang Liu, Cinobufagin overcomes bortezomib resistance in multiple myeloma strains by targeting SEC62/TRPM4-mediated NECSO, Phytomedicine, 2025, 157171, ISSN 0944-7113, https://doi.org/10.1016/j.phymed.2025.157171. August 16, 2025.
Overview
Researchers are uncovering new ways to tackle one of the toughest challenges in multiple myeloma: resistance to Velcade® (bortezomib). A recent study focused on a compound called cinobufagin, which showed promise in reversing this resistance by triggering a unique type of cell death known as necrosis by sodium overload (NECSO). Until now, little was known about NECSO, except that it involves the protein TRPM4, which is reduced in patients and cells that no longer respond to bortezomib.
In lab experiments, cinobufagin slowed the growth of bortezomib-resistant myeloma cells and, in mouse models, suppressed tumor growth while reducing markers of cancer activity. The researchers discovered that cinobufagin works by stabilizing TRPM4. Normally, TRPM4 is broken down when it interacts with another protein, SEC62. Cinobufagin disrupts this interaction, preventing TRPM4 from being degraded and restoring its activity. This stabilization, in turn, activates the NECSO pathway and leads to cancer cell death.
Importantly, when SEC62 was knocked down, cinobufagin lost much of its effect, confirming SEC62’s central role in this process. By targeting the SEC62-TRPM4 axis, cinobufagin not only overcomes bortezomib resistance but also introduces NECSO as a novel therapeutic pathway in myeloma. These findings suggest that TRPM4 could become a valuable target for future treatments, and cinobufagin may offer a new strategy for patients whose disease has stopped responding to existing therapies.
"Poor prognosis of newly diagnosed multiple myeloma patients with 1p32.3 deletion in single monoallelic deletion and/or in main clone"
Source
You H, Yao W, Yan L, Zhai Y, Yan Z, Shang J, et al. Poor prognosis of newly diagnosed multiple myeloma patients with 1p32.3 deletion in single monoallelic deletion and/or in main clone. Br J Haematol. 2025; 00: 1–12. https://doi.org/10.1111/bjh.70015 August 17, 2025.
Overview
A recent study from China examined a specific genetic abnormality called del(1p32.3) in patients with newly diagnosed multiple myeloma. This genetic deletion involves the loss of part of chromosome 1 and affects a gene called CDKN2C. While doctors in China don't routinely test for this abnormality, researchers wanted to understand how it impacts patient outcomes and treatment responses.
The study analyzed 345 patients with newly diagnosed multiple myeloma using advanced genetic testing methods. The researchers found that problems with chromosome 1 were quite common, occurring in about 64% of patients. Among these cases, 40 patients specifically had the del(1p32.3) deletion. What made this finding particularly concerning was that patients with del(1p32.3) almost always had other serious genetic problems as well, including 1q21 gain or amplification and 17p deletion.
Patients with del(1p32.3) were more likely to have multiple myeloma that had spread outside the bone marrow, a condition called extra-medullary disease. They also had more complex genetic abnormalities overall, which typically indicates a more aggressive form of cancer. The study showed that having del(1p32.3) significantly shortened both progression-free survival and overall survival compared to patients without this deletion.
The prognosis was especially poor when del(1p32.3) occurred alongside 1q21 gain or amplification, suggesting these genetic changes work together to make the cancer more dangerous. Patients whose main cancer cells carried the deletion, or those with certain types of single deletions, had the worst outcomes of all. Even aggressive treatments like autologous stem cell transplantation couldn't fully overcome the negative effects of this genetic abnormality.
Standard treatment with lenalidomide, bortezomib, and dexamethasone followed by stem cell transplantation was less effective in patients with del(1p32.3). The deletion remained an independent risk factor for disease progression even when researchers accounted for other factors that influence prognosis. Based on these findings, the researchers strongly recommend that doctors begin routinely testing for del(1p32.3) in multiple myeloma patients, as it provides important information about how aggressive the disease is likely to be and how patients might respond to treatment.
"Evaluation of Delayed Initiation of Lenalidomide Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma"
Source
Kawamura, Koji, Nobuhiro Tsukada, Shun-ichi Kimura, et al. 2025. “Evaluation of Delayed Initiation of Lenalidomide Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.” Hematological Oncology: e70129. https://doi.org/10.1002/hon.70129. August 17, 2025.
Overview
A clinical study examined whether Revlimid® (lenalidomide) maintenance therapy could safely help prevent multiple myeloma from returning after allogeneic stem cell transplantation. While this type of transplant using donor cells can potentially cure multiple myeloma, the cancer often comes back, which remains a major challenge for patients and doctors.
Lenalidomide is a drug that helps the immune system fight cancer and has proven effective in treating multiple myeloma. However, doctors have been cautious about using it after allogeneic transplants because it might increase the risk of graft-versus-host disease, a serious complication where the donated immune cells attack the patient's healthy tissues.
The researchers conducted a phase I/II trial from 2014 to 2019 to find the highest safe dose of lenalidomide for maintenance therapy after transplant. They enrolled 10 patients and started lenalidomide treatment between 100 and 365 days after their transplants. Patients took the drug for 21 days out of every 28-day cycle, beginning with a low dose of 5 mg daily and gradually increasing the dose to find the maximum amount that could be given safely.
Nine patients were able to complete the safety evaluation, with one patient excluded because their cancer progressed too quickly. The study found that 10 mg daily was the highest safe dose. At this level, only one patient developed moderate chronic graft-versus-host disease that met the criteria for being a dose-limiting side effect. No patients experienced acute graft-versus-host disease, and two other patients developed mild chronic forms that went away on their own without needing treatment.
The timing of when patients started lenalidomide varied, with the average being about 8 months after transplant. Looking at outcomes two years after starting maintenance therapy, 53% of patients remained free of cancer progression and 78% were still alive. The researchers concluded that starting lenalidomide maintenance therapy at 10 mg daily several months after allogeneic transplant appears to be safe and causes relatively few problems with graft-versus-host disease. However, they emphasized that larger studies are needed to determine how well this approach actually prevents the cancer from returning compared to not using maintenance therapy.
"Mindfulness vs. sleep education during autologous hematopoietic cell transplantation for multiple myeloma: Feasibility of a randomized controlled pilot study"
Source
Elisabeth C. Henley, Hannah A. Liphart, Keayra J. Morris, Iwalola Awoyinka, Michael R. Irwin, Erin S. Costanzo, Diana Winston, Anita D’Souza, Melinda Stolley, Binod Dhakal, Meera Mohan, Marcelo C. Pasquini, Steven W. Cole, Erin S. Doerwald, Peyton C. Bendis, Kelly E. Rentscher, Meredith E. Rumble, Aniko Szabo, Sridhar Rao, Jennifer M. Knight, Mindfulness vs. sleep education during autologous hematopoietic cell transplantation for multiple myeloma: Feasibility of a randomized controlled pilot study, Contemporary Clinical Trials Communications, 2025, 101540, ISSN 2451-8654, https://doi.org/10.1016/j.conctc.2025.101540. August 18, 2025.
Overview
Researchers conducted a pilot study to test whether a mindfulness-based program could help multiple myeloma patients sleep better during autologous stem cell transplantation. Sleep problems are very common during this treatment, and previous research suggested that mindfulness interventions might improve sleep quality by reducing treatment side effects and boosting immune function.
The study compared two different approaches to helping patients with sleep issues. One group received Mindfulness Awareness Practices for Insomnia, known as MAP-I, while the other group got Sleep Health Education. Both programs included six educational videos that patients watched before their transplant, plus three virtual sessions with an instructor during the two weeks after transplant. The researchers wanted to see if this type of program was practical to run during such an intensive treatment period.
To consider the study successful, the researchers needed to enroll at least 35% of eligible patients and keep 85% of those enrolled through the entire program. They screened 120 patients with multiple myeloma who were planning to have autologous stem cell transplants. Of these, 54 patients were not eligible for various reasons, and 42 patients chose not to participate. This left 24 patients who agreed to join the study, which met the enrollment goal with a 36.4% participation rate.
Unfortunately, keeping patients in the study proved much more challenging than getting them to sign up initially. Only seven patients out of the original 24 completed the full program, resulting in a retention rate of just 29.2%, which was far below the target of 85%. Most patients who dropped out explained that they felt too overwhelmed or too sick after their transplant to continue with the study activities and virtual sessions.
The researchers tried several changes during the study to improve participation rates. They added financial incentives for completing the program, adjusted when patients needed to watch the videos, and introduced the mindfulness instructor earlier in the process. However, these modifications weren't enough to overcome the fundamental challenge that patients felt too unwell during the transplant period to engage with the intervention.
The study revealed important insights about the timing of supportive care interventions for transplant patients. While patients were willing to try mindfulness-based sleep programs, the period immediately surrounding stem cell transplantation may be too physically and emotionally demanding for many people to participate in additional activities, even those designed to help them feel better. The researchers concluded that future studies should explore offering mindfulness interventions at different times during the transplant process when patients might be better able to participate and benefit from the program.
"De-escalated Teclistamab dosing in relapsed/refractory multiple myeloma: Czech myeloma group real-world evidence analysis"
Source
Stork, M., Radocha, J., Mihalyova, J. et al. De-escalated Teclistamab dosing in relapsed/refractory multiple myeloma: Czech myeloma group real-world evidence analysis. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06529-1 August 18, 2025.
Overview
A recent real-world study examined how Tecvayli® (teclistamab), a bispecific antibody that targets both BCMA and CD3, is being used outside of clinical trials to treat patients with relapsed or refractory multiple myeloma. While teclistamab has shown impressive results in clinical studies, doctors needed more information about the best dosing strategies when using it in everyday practice.
Researchers from the Czech Myeloma Group analyzed data from 73 patients with heavily pretreated multiple myeloma who received teclistamab between 2023 and 2025. The patients had a median age of 67 years, and most were considered penta-refractory, meaning their cancer had stopped responding to five major types of multiple myeloma treatments. This represented a very challenging patient population with limited treatment options.
The study compared two different dosing approaches. Some patients continued with the standard weekly dosing schedule used in clinical trials, while others had their dosing frequency reduced based on their doctor's judgment. About one-quarter of patients had their dosing reduced, and this change typically happened within the first month of starting treatment. Despite receiving a significantly lower total dose of the medication, patients in the reduced-frequency group maintained similar effectiveness.
The results showed that both dosing strategies produced comparable outcomes. The median progression-free survival was 9.41 months for the entire group, with weekly dosing patients averaging 9.1 months and reduced-frequency patients averaging 11.3 months. This difference was not statistically significant, even though the reduced-frequency group received only 60.5% of the standard dose intensity compared to 87% in the weekly group.
Safety profiles were generally similar between the two dosing approaches. Both groups experienced comparable rates of infections and severe side effects, which are known concerns with teclistamab treatment. Interestingly, patients on reduced-frequency dosing had lower rates of neutropenia, a condition where white blood cell counts drop dangerously low. However, this improvement in blood counts didn't translate into fewer infections, suggesting that other factors may influence infection risk in these patients.
These findings suggest that doctors can safely reduce teclistamab dosing frequency early in treatment without compromising its effectiveness against multiple myeloma. This flexibility in dosing could be particularly valuable for managing side effects and improving patients' quality of life while maintaining cancer control. The study supports ongoing efforts to personalize treatment schedules, allowing doctors to balance the benefits of cancer treatment with the goal of minimizing side effects for each individual patient.
"Association of product of platelet and neutrophil count with monoclonal gammopathy of undetermined significance: a cross-sectional analysis of the NHANES"
Source
Wang, L., Yang, P., Nan, H. et al. Association of product of platelet and neutrophil count with monoclonal gammopathy of undetermined significance: a cross-sectional analysis of the NHANES. Blood Res. 60, 46 (2025). https://doi.org/10.1007/s44313-025-00094-2 August 18, 2025.
Overview
A large study examined whether inflammation markers in the blood might be connected to the development of MGUS, a precancerous condition that can sometimes progress to multiple myeloma. Since chronic inflammation may play a role in driving MGUS toward becoming cancer, researchers wanted to understand if certain blood tests could help identify people at higher risk.
The study analyzed data from 6,383 participants in the National Health and Nutrition Examination Survey, which is a major health study conducted in the United States. Among these participants, 157 people (2.45%) had MGUS, which was identified using specialized protein tests. The researchers looked at seven different inflammation markers that can be calculated from routine blood tests, including counts of various white blood cells, platelets, and C-reactive protein levels.
One marker that stood out was called the platelet-neutrophil product, or PPN, which combines platelet and neutrophil counts into a single number. The study found a significant relationship between PPN levels and the likelihood of having MGUS, particularly when PPN levels were low. People with lower PPN levels were about 2.6 times more likely to have MGUS compared to those with higher levels. Interestingly, other inflammation markers like the platelet-lymphocyte ratio didn't show the same clear connection.
The researchers also looked at different groups of people to see if the relationship between PPN and MGUS was consistent across various populations. They found that the association was strongest in certain groups, including women, non-Hispanic Black individuals, people without high cholesterol or type 2 diabetes, those with at least a high school education, and people who were divorced or widowed. However, the overall pattern held true across the general population.
These findings suggest that PPN could potentially serve as a simple and convenient way to assess MGUS risk using standard blood tests that doctors already order regularly. Since PPN can be calculated from a basic complete blood count, it wouldn't require any additional testing or expense for patients. This could make it a practical tool for identifying people who might benefit from closer monitoring or earlier screening for MGUS.
The researchers emphasized that these results are preliminary and need to be confirmed through longer-term studies that follow people over time. While the association between low PPN levels and MGUS is intriguing, more research is needed to understand whether this marker could actually be useful in clinical practice for predicting who might develop MGUS or tracking how the condition progresses over time.
"T cell redirecting therapy for relapsed multiple myeloma"
Source
Tan, M.S.Y., Hellou, T. & Dingli, D. T cell redirecting therapy for relapsed multiple myeloma. Discov Onc 16, 1573 (2025). https://doi.org/10.1007/s12672-025-03432-z August 18, 2025.
Overview
The treatment of multiple myeloma has improved dramatically over the past several years thanks to three major classes of drugs: immunomodulatory drugs like lenalidomide, proteasome inhibitors such as bortezomib, and monoclonal antibodies that target CD38. These medications have helped patients live longer and have better quality of life compared to older treatments. However, despite these advances, multiple myeloma almost always comes back after treatment, and until recently, patients who had tried multiple therapies had very limited options and poor outcomes.
The landscape changed significantly with the introduction of two groundbreaking immunotherapy approaches: CAR T-cell therapy and T-cell engagers. CAR T-cell therapy involves taking a patient's own immune cells, genetically modifying them in a laboratory to better recognize and attack myeloma cells, then infusing them back into the patient. T-cell engagers are medications that work by bringing the patient's existing T-cells into direct contact with myeloma cells, essentially teaching the immune system to fight the cancer more effectively.
These new immunotherapies have been particularly valuable for patients with triple-class refractory disease, meaning their myeloma no longer responds to all three major drug categories, and penta-class refractory disease, where the cancer has become resistant to five different types of treatments. Before these immunotherapies became available, such patients had very few treatment options and typically faced a poor prognosis. Now, many of these heavily pretreated patients are achieving significant responses and living much longer than previously expected.
However, these powerful new treatments come with their own unique challenges and side effects that doctors and patients need to understand and manage carefully. The review examines the clinical results from studies of these immunotherapies, including both their effectiveness and their potential complications. It also discusses the important question of when and in what order these treatments should be used as part of a patient's overall treatment plan, since the sequence of different therapies can impact how well each one works.
Managing patients receiving these advanced immunotherapies requires specialized supportive care to help prevent and treat side effects. This includes careful monitoring for complications and providing additional treatments to help patients tolerate the immunotherapy and maintain their strength during treatment. The review emphasizes that successful outcomes depend not just on the immunotherapy itself, but on comprehensive care that addresses all aspects of the patient's health.
Looking toward the future, researchers are continuing to develop even more innovative immunotherapy approaches for relapsed multiple myeloma. The review concludes by discussing some of these emerging treatments that are currently being studied and may become available in the coming years, offering hope for even better outcomes for patients whose myeloma returns after current treatments.
"Efficacy of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma and prior central nervous system manifestation: A multicenter real-world analysis"
Source
Maulhardt, M., Call, S., Boyadzhiev, H., Albici, A.M., Hörster, K., Boquoi, A., Janjetovic, S., Ossami Saidy, A., Teichert, M., Brioli, A., Schultze-Florey, C., Heidel, F., Schindler, P., Schub, N., Aydilek, E., Stelljes, M., Daskalakis, M., Krekeler, C., Hasenkamp, J., Khandanpour, C., Bacher, U., Reinhardt, H.C., Lenz, G., Stölzel, F., Pabst, T., von Tresckow, B., Wulf, G., Berning, P. and Shumilov, E. (2025), Efficacy of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma and prior central nervous system manifestation: A multicenter real-world analysis. HemaSphere, 9: e70192. https://doi.org/10.1002/hem3.70192 August 18, 2025.
Overview
The treatment of multiple myeloma has improved dramatically over the past several years thanks to three major classes of drugs: immunomodulatory drugs like Revlimid® (lenalidomide), proteasome inhibitors such as Velcade® (bortezomib), and monoclonal antibodies that target CD38. These medications have helped patients live longer and have better quality of life compared to older treatments. However, despite these advances, multiple myeloma almost always comes back after treatment, and until recently, patients who had tried multiple therapies had very limited options and poor outcomes.
The landscape changed significantly with the introduction of two groundbreaking immunotherapy approaches: CAR T-cell therapy and T-cell engagers. CAR T-cell therapy involves taking a patient's own immune cells, genetically modifying them in a laboratory to better recognize and attack myeloma cells, then infusing them back into the patient. T-cell engagers are medications that work by bringing the patient's existing T-cells into direct contact with myeloma cells, essentially teaching the immune system to fight the cancer more effectively.
These new immunotherapies have been particularly valuable for patients with triple-class refractory disease, meaning their myeloma no longer responds to all three major drug categories, and penta-class refractory disease, where the cancer has become resistant to five different types of treatments. Before these immunotherapies became available, such patients had very few treatment options and typically faced a poor prognosis. Now, many of these heavily pretreated patients are achieving significant responses and living much longer than previously expected.
However, these powerful new treatments come with their own unique challenges and side effects that doctors and patients need to understand and manage carefully. The review examines the clinical results from studies of these immunotherapies, including both their effectiveness and their potential complications. It also discusses the important question of when and in what order these treatments should be used as part of a patient's overall treatment plan, since the sequence of different therapies can impact how well each one works.
Managing patients receiving these advanced immunotherapies requires specialized supportive care to help prevent and treat side effects. This includes careful monitoring for complications and providing additional treatments to help patients tolerate the immunotherapy and maintain their strength during treatment. The review emphasizes that successful outcomes depend not just on the immunotherapy itself, but on comprehensive care that addresses all aspects of the patient's health.
Looking toward the future, researchers are continuing to develop even more innovative immunotherapy approaches for relapsed multiple myeloma. The review concludes by discussing some of these emerging treatments that are currently being studied and may become available in the coming years, offering hope for even better outcomes for patients whose myeloma returns after current treatments.
"Syntenin inhibition impairs stroma-tumor communication in multiple myeloma and improves bortezomib treatment efficiency"
Source
Tu, C., Leblanc, R., Van der Vreken, A., Koops, M., Audebert, S., Goullieux, L., Meeussen, S., De Veirman, K., De Bruyne, E., Vanderkerken, K., David, G., Cupedo, T., Zimmermann, P. and Menu, E. (2025), Syntenin inhibition impairs stroma-tumor communication in multiple myeloma and improves bortezomib treatment efficiency. HemaSphere, 9: e70197. https://doi.org/10.1002/hem3.70197 August 18, 2025.
Overview
Multiple myeloma remains a challenging cancer to cure because it eventually develops resistance to most treatments. Previous research has shown that bone marrow stromal cells, which are the supporting cells in the bone marrow environment, communicate with myeloma cells in ways that help the cancer grow and become resistant to therapy. This harmful communication happens through several mechanisms, including the release of signaling molecules called cytokines and tiny packages called small extracellular vesicles that carry messages between cells.
A protein called syntenin acts as a master controller of how cells communicate with each other, particularly through these small extracellular vesicles. Researchers wanted to investigate whether blocking syntenin, either by removing it genetically or using drugs to inhibit it, could disrupt the harmful communication between bone marrow stromal cells and myeloma cells. Their goal was to make myeloma cells more vulnerable to treatment by cutting off this supportive communication.
The study found that syntenin levels are very high in inflammatory bone marrow stromal cells taken from multiple myeloma patients. More importantly, when syntenin expression was high in bone marrow samples, patients tended to have worse survival outcomes. This suggested that syntenin might be playing an important role in making the disease more aggressive and harder to treat.
Using laboratory experiments, the researchers discovered that removing syntenin from bone marrow stromal cells changed what these cells secreted into their surrounding environment. Without syntenin, the stromal cells could no longer protect myeloma cells from bortezomib, a common multiple myeloma treatment. The protection mechanism involved several important cellular pathways, including STAT3, MAPK, and AKT-mTOR, which are known to help cancer cells survive and resist treatment.
When the researchers used drugs to block syntenin function, they found that this reduced the amount of syntenin and IL-6, an important growth factor, that got packaged into the small extracellular vesicles released by bone marrow stromal cells. This change made bortezomib much more effective at killing myeloma cells, suggesting that blocking syntenin could enhance the effectiveness of existing treatments.
The researchers also tested their findings in living mice using a well-established multiple myeloma model called 5TGM1. The combination of syntenin inhibition with bortezomib proved more effective than bortezomib alone, confirming that this approach has therapeutic potential. The study concludes that syntenin helps bone marrow stromal cells secrete factors that promote tumor growth and protect myeloma cells from treatment. This makes syntenin a promising new target for developing combination therapies that could overcome treatment resistance and improve outcomes for multiple myeloma patients.
"D-VMP elicits clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma"
Source
Nierengarten, M.B. (2025), D-VMP elicits clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma. Cancer, 131: e70001. https://doi.org/10.1002/cncr.70001 August 18, 2025.
Overview
The final results from the ALCYONE trial confirm the long-term benefits of adding Darzalex® (daratumumab) to standard treatment for newly diagnosed multiple myeloma patients who are not candidates for stem cell transplantation. After more than seven years of follow-up, patients who received the four-drug combination of daratumumab, Velcade® (bortezomib), melphalan, and prednisone (D-VMP) lived significantly longer than those who received only the three-drug combination of bortezomib, melphalan, and prednisone (VMP).
The survival difference was substantial and clinically meaningful. Patients treated with D-VMP had a median overall survival of 83 months compared to 53.6 months for those receiving VMP alone. This represents a 35% reduction in the risk of death when daratumumab was added to the treatment regimen. These impressive survival results build upon earlier findings from the same trial that showed D-VMP was superior to VMP in several other important measures, including keeping the disease from progressing, achieving better response rates, and eliminating detectable cancer cells from the body.
The ALCYONE study was groundbreaking because it was the first phase 3 trial to directly compare a four-drug induction regimen against a three-drug regimen in this patient population. The study enrolled 706 patients who were at least 18 years old with newly diagnosed multiple myeloma and were not eligible for high-dose chemotherapy or stem cell transplantation due to age, other health conditions, or personal preference.
Dr. Ajay Nooka from Emory University's Winship Cancer Institute placed these results in context with other important studies of daratumumab-containing regimens. He noted that while the MAIA trial established daratumumab combined with lenalidomide and dexamethasone as the current standard of care in the United States, the overall survival data from ALCYONE provides valuable insight into what we might expect from other daratumumab-based combinations. The MAIA regimen showed significant improvements in progression-free survival, but overall survival data from that study are not yet mature enough to analyze.
Both experts acknowledged that daratumumab-containing regimens do carry an increased risk of infections, particularly pneumonia, compared to treatments without daratumumab. Dr. Nooka emphasized the importance of careful monitoring for viral reactivations, including hepatitis B, and recommended routine use of antiviral medications like acyclovir or valacyclovir. While routine antibiotic prevention is not recommended, doctors should have a low threshold for starting antibiotics if any signs of infection appear.
Dr. Maria-Victoria Mateos, the study's lead author from the University of Salamanca, highlighted an important practical advantage of the D-VMP regimen. While the standard daratumumab, lenalidomide, and dexamethasone combination requires continuous treatment, D-VMP involves the full four-drug combination for only the first year, followed by monthly daratumumab injections under the skin. This approach may be more convenient for patients and could reduce the long-term treatment burden while maintaining the survival benefits demonstrated in this landmark trial.
"Population Exposure–Response Efficacy Analysis of Elranatamab (PF-06863135) in Patients with Multiple Myeloma"
Source
Lon, HK., Hibma, J., Jiang, S. et al. Population Exposure–Response Efficacy Analysis of Elranatamab (PF-06863135) in Patients with Multiple Myeloma. Targ Oncol (2025). https://doi.org/10.1007/s11523-025-01168-y August 18, 2025.
Overview
Elrexfio® (elranatamab) is a bispecific antibody that works by connecting two important targets: BCMA, which is found on multiple myeloma cells, and CD3, which is found on immune T-cells. This connection helps the patient's immune system recognize and attack the myeloma cells more effectively. Results from the MagnetisMM-3 study showed that elranatamab produced deep and long-lasting responses in patients with relapsed or refractory multiple myeloma who had already tried multiple other treatments.
Researchers wanted to better understand how the amount of free elranatamab in a patient's bloodstream relates to how well the treatment works. They specifically looked at the relationship between drug levels and several important outcomes, including overall response rates, complete response rates, progression-free survival, and how long responses lasted. They also examined whether other factors might influence these relationships between drug exposure and treatment effectiveness.
The analysis combined data from four different clinical studies that tested elranatamab at various dose levels, providing information on 312 patients whose responses could be evaluated. The researchers used sophisticated statistical methods to analyze the relationships, including logistic regression for response rates and survival analysis methods for time-based outcomes like progression-free survival and duration of response.
The results showed clear patterns between drug exposure and treatment effectiveness. Patients with higher levels of free elranatamab in their blood were more likely to achieve both overall responses and complete responses to treatment. Additionally, patients with lower levels of soluble BCMA, a protein that can interfere with the drug's effectiveness, also had better response rates. This suggests that both having enough drug in the system and having fewer interfering factors contribute to better outcomes.
For progression-free survival, the relationship was more complex. Higher drug exposure was associated with longer periods without disease progression, but this benefit was mainly seen in the early treatment cycles when patients either responded quickly or progressed rapidly. After these initial cycles, the relationship between drug levels and progression-free survival became less clear. Interestingly, the researchers found no clear relationship between drug exposure and how long responses lasted once they were achieved.
These findings provide important validation for the current dosing approach used with elranatamab. The analysis supports starting treatment with the approved initial dosing schedule, which ensures patients get adequate drug exposure to maximize their chances of responding. The results also support the practice of switching to less frequent dosing in patients who are responding well during later treatment cycles, since maintaining very high drug levels doesn't appear to be necessary once a response is established. This flexibility in dosing can help reduce treatment burden and side effects while maintaining effectiveness for patients who are benefiting from elranatamab therapy.
"MATCH: a flexible and safer approach to T cell–based immunotherapy for multiple myeloma"
Source
Li, S. Spotlighting rising researcher Shannuo Li: MATCH: a flexible and safer approach to T cell–based immunotherapy for multiple myeloma. AAPS Open 11, 18 (2025). https://doi.org/10.1186/s41120-025-00124-4 August 19, 2025
Overview
Researchers at the University of Utah have developed a groundbreaking new approach to treating multiple myeloma that could make immunotherapy both safer and more personalized. The innovative platform, called Multi-Antigen T Cell Hybridizers or MATCH, represents a significant advance over current bispecific antibody treatments like teclistamab by offering a modular, customizable system that can be tailored to each patient's unique cancer profile.
The MATCH system works differently from traditional immunotherapies by using two separate components that only become active when they come together at the tumor site. The first component targets specific proteins found on multiple myeloma cells, such as BCMA, CD38, or SLAMF7, while the second component binds to T-cells through the CD3 protein. These components are connected by complementary molecular sequences called morpholino oligonucleotides that act like biological Velcro, allowing them to stick together only when both are present in the right place.
What makes MATCH particularly innovative is its modular design, which allows doctors to mix and match different tumor-targeting components based on what proteins are most abundant on a patient's specific cancer cells. Since multiple myeloma can vary significantly between patients in terms of which surface proteins are present, this flexibility could lead to more effective personalized treatment strategies. Additionally, because the system uses two separate components, doctors can administer them at different times, which may help reduce side effects.
The sequential dosing approach is one of MATCH's key safety advantages. The tumor-targeting component is given first and allowed time to find and attach to cancer cells throughout the body. After unbound drug clears from the bloodstream, the T-cell engaging component is administered. This stepwise process means the active bispecific complex forms primarily where cancer cells are located, potentially reducing the risk of cytokine release syndrome and other serious side effects that can occur when the immune system becomes overactivated throughout the body.
Laboratory studies have shown promising results across multiple testing scenarios. When researchers tested MATCH on human multiple myeloma cell lines in the laboratory, the treatment consistently triggered strong T-cell activation and effectively killed cancer cells at very low concentrations. The mechanism involves T-cells releasing toxic substances like granzymes and perforin, along with important signaling molecules that ultimately cause cancer cells to die through a controlled process called apoptosis.
Perhaps more importantly, the researchers tested MATCH on bone marrow samples taken directly from multiple myeloma patients. Thirteen out of sixteen patient samples showed significant cancer cell death when treated with MATCH, even though the patients had different patterns of surface proteins on their cancer cells. This real-world relevance demonstrates that MATCH's modular approach could work across the diverse range of multiple myeloma cases seen in clinical practice.
Animal studies using humanized mice provided additional validation of both effectiveness and safety. Mice treated with MATCH lived significantly longer and had much smaller tumors compared to those treated with teclistamab, an FDA-approved bispecific T-cell engager currently used in clinical practice. Importantly, blood tests showed that MATCH caused much lower levels of inflammatory molecules in the bloodstream, suggesting it produces fewer systemic side effects while maintaining strong anti-cancer activity.
The research team's broader vision extends beyond multiple myeloma treatment to include applications for other blood cancers and even the possibility of engaging other immune cells like natural killer cells and macrophages. They are also exploring ways to combine MATCH with checkpoint inhibitors, which could help T-cells stay active longer and fight cancer more persistently. The programmable nature of the system opens up possibilities for creating even more sophisticated treatments that can distinguish between healthy and cancerous cells with greater precision, potentially leading to the next generation of safer and more effective personalized immunotherapies.
"Early peripheral blood and bone marrow MRD as prognostic markers in quadruplet-treated multiple myeloma without transplant"
Source
Derman, B.A., Cooperrider, J., Pula, A., Simmons, H., Kubicki, T., Zonder, J., Afrough, A., Grinblatt, D., Rosenblatt, J., Anderson, L.D., Jr., Kin, A., Avigan, D., Narula, S., Rayani, S., Jiang, K., Major, A., Karrison, T., Jacob, A. and Jakubowiak, A.J. (2025), Early peripheral blood and bone marrow MRD as prognostic markers in quadruplet-treated multiple myeloma without transplant. HemaSphere, 9: e70186. https://doi.org/10.1002/hem3.70186 August 19, 2025.
Overview
Researchers have discovered that testing for measurable residual disease in both blood and bone marrow samples after just four cycles of treatment can provide valuable information about multiple myeloma patients' prognosis and help guide treatment decisions. This approach may be more informative than traditional response measurements and could help doctors personalize treatment strategies more effectively.
The study analyzed data from two clinical trials that tested powerful four-drug combinations in newly diagnosed multiple myeloma patients who were not planning to have stem cell transplants. One trial used elotuzumab combined with carfilzomib, lenalidomide, and dexamethasone, while the other used daratumumab with the same three-drug backbone. After four treatment cycles, researchers used advanced genetic sequencing technology called next-generation sequencing to look for any remaining cancer cells in both bone marrow and peripheral blood samples.
Among 62 patients who completed four cycles of treatment, the researchers found important differences between what traditional response criteria showed versus what the more sensitive MRD testing revealed. While 31% of patients achieved complete responses according to standard criteria, the MRD testing provided much more detailed information about actual disease burden. Importantly, achieving a complete response by traditional standards did not predict better long-term outcomes, but MRD results were strongly linked to how patients fared over time.
The bone marrow MRD results showed that 34% of patients had no detectable disease at very low levels after four cycles. Patients who achieved this deep level of response had significantly better progression-free survival and overall survival compared to those who still had detectable disease. This suggests that achieving MRD negativity in bone marrow early in treatment may identify patients who could potentially avoid more intensive treatments like stem cell transplantation.
Blood-based MRD testing proved even more predictive of outcomes than bone marrow testing. Among the patients tested, 74% had no detectable cancer cells in their blood samples after four treatment cycles. Patients with positive blood MRD results had much higher risks of disease progression and death, with four-year progression-free survival rates of only 40% compared to 83% for those with negative blood tests. This blood-based approach offers the advantage of being less invasive than repeated bone marrow biopsies.
When researchers compared blood and bone marrow MRD results from the same patients, they found that the tests often gave different information. Only about half of the paired results agreed with each other, suggesting that each test provides unique insights into the patient's disease status. Interestingly, almost all patients with positive blood MRD also had positive bone marrow MRD, but many patients with positive bone marrow MRD had negative blood tests.
The combination of both blood and bone marrow MRD testing provided the most comprehensive picture of patient prognosis. Patients who were positive for MRD in both compartments had the worst outcomes, while those negative in both had the best results. Patients with mixed results fell somewhere in between, highlighting the value of testing both sites to get a complete assessment of treatment response.
These findings have important implications for personalizing multiple myeloma treatment. Patients who achieve MRD negativity in bone marrow after four cycles might be candidates for less intensive treatment approaches, potentially avoiding the risks and side effects of stem cell transplantation. Conversely, patients with positive blood MRD represent a high-risk group who might benefit from more aggressive treatments, including earlier transplantation or even newer therapies like CAR T-cell treatment. The researchers emphasize that future clinical trials should incorporate both blood and bone marrow MRD testing to help doctors make more informed decisions about treatment intensity based on each patient's individual response patterns.
"Radiomics feature analysis for survival prediction in multiple myeloma: An automated PET/CT approach"
Source
Javier Guinea-Pérez, Alessandro Ceresi, Anaida Fernández García, Borja Arroyo Galende, Alberto Belmonte-Hernández, Sara Peluso, Federico Alvarez, Radiomics feature analysis for survival prediction in multiple myeloma: An automated PET/CT approach, Computer Methods and Programs in Biomedicine, 2025, 109019, ISSN 0169-2607, https://doi.org/10.1016/j.cmpb.2025.109019. August 19, 2025.
Overview
Researchers have developed an automated computer analysis system that can analyze PET/CT scans to help predict how long multiple myeloma patients will remain free of disease progression. This artificial intelligence approach uses advanced image analysis techniques called radiomics to extract detailed information from medical scans that might not be visible to the human eye, potentially providing doctors with better tools for assessing patient prognosis.
The study analyzed whole-body PET/CT scans from 227 multiple myeloma patients using a fully automated computer pipeline. The system first identified and segmented different parts of the skeleton, particularly focusing on the spine and surrounding areas where multiple myeloma commonly affects bone. The researchers then extracted hundreds of mathematical features from these images that describe various characteristics like texture, shape, and intensity patterns that could be related to disease activity.
To determine which parts of the body provided the most useful information for predicting outcomes, the researchers created different masks or regions of interest focusing on various skeletal areas. They tested different combinations of these regions along with both PET and CT image data to see which approach gave the best results. Four different types of artificial intelligence models were trained and tested to predict progression-free survival, with the researchers evaluating 128 different combinations of models, image types, and body regions.
The best-performing system was a deep learning model called DeepSurv that used only PET scan information from the spine and the area immediately around it. This model achieved a c-index of 0.657, which indicates moderately good ability to rank patients according to their risk of disease progression. Interestingly, while combining both PET and CT information generally improved results, the single best model relied solely on PET data, suggesting that the metabolic information captured by PET scans may be more important than the structural details from CT scans.
The analysis revealed that texture features were the most important for predicting patient outcomes. These features measure how uniform or varied the appearance of tissues is within the scan images. Patients whose scans showed more heterogeneity, meaning more variation in texture patterns, had higher risks of disease progression. This makes biological sense, as more heterogeneous tissue patterns often reflect more aggressive or advanced disease states.
When comparing different approaches to selecting which parts of the body to analyze, the researchers found that including the paramedullary region around the spine was important for getting good results. However, expanding the analysis to include the entire skeleton did not improve predictions, suggesting that focusing on specific high-yield areas may be more effective than trying to analyze everything. The spine region appears to be particularly informative, likely because it is commonly affected by multiple myeloma and represents a good sampling of overall disease activity.
The study demonstrates that artificial intelligence can extract meaningful prognostic information from routine medical scans that multiple myeloma patients already receive as part of their standard care. While the predictive performance was moderate rather than excellent, this automated approach could potentially be integrated into clinical practice to help doctors better understand each patient's risk profile. The researchers have made their computer pipeline publicly available, which could help other medical centers implement and further develop this technology. Future studies will likely focus on improving the prediction accuracy and validating these findings in larger, diverse patient populations to determine how this technology might best be used to guide treatment decisions.
"Temporal genomic dynamics shape clinical trajectory in multiple myeloma"
Source
Maura, F., Kaddoura, M., Poos, A.M. et al. Temporal genomic dynamics shape clinical trajectory in multiple myeloma. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02292-1 August 20, 2025.
Overview
Researchers conducted a comprehensive analysis of 421 whole-genome sequences from 382 multiple myeloma patients to understand how the disease develops over time and how the timing of genetic changes affects patient outcomes. By studying the accumulation of genetic alterations throughout the cancer's evolution, they discovered that multiple myeloma has a much longer development timeline than previously understood, with important implications for predicting patient prognosis.
Using sophisticated molecular clock techniques that can estimate when genetic changes occurred, the researchers found that multiple myeloma begins developing two to four decades before patients are actually diagnosed with the disease. This finding reveals that the cancer has an extremely long preclinical phase, during which genetic alterations slowly accumulate in cells before the disease becomes clinically apparent. This extended timeline helps explain why multiple myeloma typically affects older adults and suggests that the disease process begins much earlier in life than doctors previously realized.
The study provided new insights into how hyperdiploidy, a condition where myeloma cells have extra copies of certain chromosomes, develops over time. The researchers discovered that the characteristic pattern of gaining odd-numbered chromosomes can happen simultaneously with other important genetic changes, such as gaining extra copies of chromosome arm 1q. This finding challenges previous assumptions about how these genetic alterations occur and suggests that multiple significant changes can happen together rather than in a strict sequential order.
When both hyperdiploidy and immunoglobulin heavy chain translocations occur in the same patient, the researchers found that hyperdiploidy is typically acquired after the translocation events. This timing information helps scientists understand the sequence of genetic events that drive multiple myeloma development and provides insights into which changes are primary drivers versus secondary events that occur as the disease progresses.
One of the most clinically significant findings involved the timing of 1q gain, a genetic alteration that has long been recognized as an important prognostic factor in multiple myeloma. The researchers discovered that patients who acquired 1q gain early in their disease development had outcomes similar to those with 1q amplification, where multiple extra copies of this chromosome region are present. Both early 1q gain and amplification were associated with worse survival compared to patients who acquired 1q gain later in their disease course.
This timing-dependent effect of 1q gain represents a paradigm shift in understanding this genetic alteration's prognostic significance. Previously, doctors focused primarily on how many extra copies of 1q were present, with more copies generally indicating worse prognosis. However, this study demonstrates that when the gain occurs may be more important than the actual number of copies gained. Patients with early 1q gain, even if they have only one extra copy, appear to have more aggressive disease than those who develop the same genetic change later.
These findings have important implications for how doctors assess prognosis and potentially plan treatment for multiple myeloma patients. Understanding the evolutionary timeline of genetic changes could help identify patients with more aggressive disease earlier in their treatment course, even when traditional markers like the extent of genetic alterations might not clearly distinguish between different risk groups. The research contributes to a growing understanding of cancer as an evolutionary process and highlights how the timing and sequence of genetic events, not just their presence, influence patient outcomes. This deeper understanding of multiple myeloma's life history may eventually lead to more personalized approaches to risk assessment and treatment planning.
"Clarithromycin, ixazomib, pomalidomide, dexamethasone for relapsed/refractory myeloma: survival and correlative analysis"
Source
Aaron S. Rosenberg, Emanual Maverakis, Caitlin Costello, Elizabeth A. Brem, Matthew Joseph Wieduwilt, Guillaume Luxardi, Paul Kaesberg, Keon Abedi, Samantha Herbert, Joseph Tuscano; Clarithromycin, ixazomib, pomalidomide, dexamethasone for relapsed/refractory myeloma: survival and correlative analysis. Blood Neoplasia 2025; 2 (3): 100067. doi: https://doi.org/10.1016/j.bneo.2025.100067 August 20, 2025.
Overview
A new four-drug combination called ClIPd, which includes the antibiotic clarithromycin along with ixazomib, pomalidomide, and dexamethasone, showed promising results in a phase 1/2 study of patients with relapsed or refractory multiple myeloma. The combination offers the convenience of all-oral administration while demonstrating impressive response rates and long-lasting disease control, even in patients with high-risk genetic features.
The study enrolled 28 patients who had previously tried multiple treatments for their multiple myeloma. The treatment approach involved giving all four medications at full doses for the first six cycles, followed by maintenance therapy where Pomalyst® (pomalidomide), Ninlaro® (ixazomib), and dexamethasone were given at reduced doses while clarithromycin continued at full strength. Patients continued treatment until their disease progressed or they experienced unacceptable side effects. Interestingly, clarithromycin was temporarily withheld during the first two weeks to allow researchers to study how the other drugs worked before the antibiotic was added.
The response rates were remarkably high across all measures of treatment effectiveness. Three-quarters of patients achieved at least a partial response, while every single patient achieved at least stable disease, meaning no patient experienced immediate disease progression. More than half of the patients achieved very good partial responses or better, and 14% achieved complete responses, indicating that their myeloma became undetectable by standard testing methods.
What made these results particularly noteworthy was that the treatment worked equally well regardless of whether patients had high-risk genetic abnormalities. Typically, patients with certain chromosomal changes like del(17p) have much more aggressive disease that responds poorly to treatment. However, in this study, patients with high-risk genetics achieved the same response rates as those with standard-risk disease, suggesting that this combination may help overcome some of the resistance associated with these challenging genetic features.
The duration of treatment benefit was also impressive, with patients experiencing a median progression-free survival of 22.2 months. This means that half of the patients remained free of disease progression for nearly two years, which is particularly encouraging given that these were heavily pretreated patients whose myeloma had already become resistant to multiple therapies. Even more striking was that patients with del(17p), typically considered very high-risk, had similar progression-free survival times to those without this genetic abnormality.
The treatment was generally well-tolerated, with researchers successfully identifying safe and effective doses for the combination. The convenience of having all medications available as oral pills rather than requiring intravenous infusions represents a significant quality-of-life advantage for patients. This oral approach allows patients to receive effective treatment at home rather than spending frequent time in infusion centers, which can be particularly valuable for patients with advanced disease who may have limited energy and mobility.
Overall survival data were not yet mature at the time of analysis, meaning that not enough patients had died to determine the median survival time, which actually suggests positive outcomes. The study demonstrates that ClIPd represents a promising treatment option that combines effectiveness with convenience and tolerability. The fact that it appears to work well even in high-risk patients makes it potentially valuable for treating some of the most challenging cases of relapsed multiple myeloma, though larger studies will be needed to confirm these encouraging initial results.
"Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma"
Source
Jan H. Frenking, Xiang Zhou, Kai Rejeski, Vivien Wagner, Patrick Costello, Thomas Hielscher, Lilan Gatti, Joseph Kauer, Omar Nadeem, Elias K. Mai, Christian S. Michel, Mirco J. Friedrich, David Sedloev, Niels Weinhold, Hartmut Goldschmidt, Klaus Herfarth, Anita Schmitt, Michael Hundemer, Michael Schmitt, Carsten Müller-Tidow, Max Topp, Hermann Einsele, Peter Dreger, Nikhil C. Munshi, Adam S. Sperling, Leo Rasche, Sandra Sauer, Marc S. Raab; Bridging intensity is associated with impaired hematopoietic recovery after BCMA CAR-T therapy for multiple myeloma. Blood Adv 2025; 9 (16): 4151–4166. doi: https://doi.org/10.1182/bloodadvances.2024015732 August 26, 2025.
Overview
Researchers have developed a simple way to classify bridging therapies used between the time multiple myeloma patients are approved for CAR-T cell treatment and when they actually receive it. Their study found that patients who received more intensive chemotherapy during this bridging period had significant problems with their blood cell recovery after CAR-T treatment, leading to dangerous drops in blood counts that required additional medical support.
The study revealed that intensive bridging chemotherapy was associated with delayed recovery of normal blood cells and a concerning pattern where blood counts would drop again weeks or months after CAR-T treatment. This second drop in blood cells led to severe cytopenias, a condition where patients don't have enough white blood cells, red blood cells, or platelets to function normally. These late-onset blood problems cannot be explained simply by the preparative chemotherapy given before CAR-T or by cytokine release syndrome, suggesting that other mechanisms are at work.
The researchers believe that intensive bridging therapy may cause both immediate and long-term damage to the bone marrow's ability to produce new blood cells. While patients might appear to recover initially, their bone marrow's reserve capacity becomes compromised, making it harder to withstand the additional stress that CAR-T cells place on the blood-forming system. This creates a situation where patients experience a delayed second hit to their blood production capabilities, leading to prolonged periods of dangerous low blood counts.
Patients who received intensive bridging therapy required significantly more supportive care after their CAR-T treatment, including more blood transfusions, growth factor injections to stimulate blood cell production, and even stem cell boosts to help restore normal blood production. The intensive bridging group also had higher rates of severe infections, likely due to both impaired immune system recovery and the preceding effects of intensive chemotherapy on their body's natural defense mechanisms.
This research adds to growing evidence that bridging therapies can have negative effects on blood cell recovery after CAR-T treatment. While some studies have questioned whether bridging therapy is always harmful, the current findings support the idea that there's a delicate balance between controlling the cancer during the waiting period and avoiding damage to the blood-forming system. Too much chemotherapy during bridging can lead to serious complications, but some treatment may be necessary to prevent the cancer from growing rapidly before CAR-T cells can be given.
The study's findings have practical implications for how doctors manage multiple myeloma patients waiting for CAR-T therapy. The researchers suggest that bridging intensity should be considered when assessing a patient's risk for complications after CAR-T treatment. High-risk patients might benefit from modified preparative regimens, more frequent monitoring, enhanced infection prevention measures, and readily available supportive treatments like growth factors and blood transfusions.
Looking toward the future, the researchers recommend that doctors be especially cautious about using high-dose alkylating agents as bridging therapy, as these drugs are particularly damaging to bone marrow. Instead, they suggest considering newer targeted therapies or even short-term use of bispecific antibodies, which may be less toxic to the blood-forming system. As CAR-T therapies become available earlier in the treatment sequence for multiple myeloma, patients may need less intensive bridging approaches, potentially reducing these complications while maintaining the effectiveness of this powerful immunotherapy approach.
"Avoid burning bridges before CAR-T therapy in myeloma"
Source
Swetha Reddi, Rahul Banerjee; Avoid burning bridges before CAR-T therapy in myeloma. Blood Adv 2025; 9 (16): 4232–4234. doi: https://doi.org/10.1182/bloodadvances.2025016774 n August 26, 2025.
Overview
Researchers recently looked at how different types of bridging therapy (BT)—the treatment patients receive while waiting for their CAR T-cell therapy—affect outcomes in multiple myeloma. In a study of 158 patients across two countries, they compared three groups: patients who received no chemotherapy or chemotherapy-free regimens, patients who received moderate amounts of chemotherapy, and patients who received intensive chemotherapy.
The results showed that intensive chemotherapy during BT was linked to more problems after CAR T-cell infusion. These patients had longer-lasting low blood counts, more frequent transfusions, and nearly 50% higher rates of severe infections compared to patients who received less or no chemotherapy. The time for white blood cells to recover was especially concerning, with a median of about two months in the intensive chemotherapy group. These lingering side effects can place a heavy burden on patients, requiring frequent clinic visits, lab tests, and supportive care long after treatment.
While doctors may sometimes recommend aggressive chemotherapy to control fast-growing disease during the wait for CAR T-cell manufacturing, the study highlights a clear downside: chemotherapy itself damages the bone marrow, worsening the risk of long-term blood count problems and infections. This is different from short-term CAR T side effects, like cytokine release syndrome, which usually resolve within days.
Experts now suggest that “more” is not better when it comes to bridging therapy. In fact, high-dose chemotherapy may do more harm than good. Newer options, such as bispecific antibodies, may provide safer and more effective ways to control the disease during this period. As CAR T therapy becomes available earlier in treatment and with newer products, the need for intensive chemotherapy bridging may decline.
Ultimately, the message is clear: burning down the disease with high-intensity chemotherapy before CAR T may actually burn the bridge to recovery, leaving patients with lasting complications instead of improved outcomes.
"Invasive fungal disease is rare in patients with relapsed/refractory multiple myeloma treated with BCMA CAR T-cell therapy"
Source
Jessica S. Little, Angelica Medina Pena, E. Bridget Kim, Andrew J. Yee, Omar Nadeem, Shonali Midha, Adam S. Sperling, Nikhil C. Munshi, Noopur Raje, Matthew J. Frigault, Diana D. Cirstea, Sarah P. Hammond; Invasive fungal disease is rare in patients with relapsed/refractory multiple myeloma treated with BCMA CAR T-cell therapy. Blood Adv 2025; 9 (16): 4190–4194. doi: https://doi.org/10.1182/bloodadvances.2025016748 August 26, 2025.
Overview
Researchers looked at how often serious fungal infections happen in people with multiple myeloma who receive BCMA CAR T-cell therapy. CAR T-cell therapy is a powerful treatment that uses a patient’s own immune cells to fight their cancer. While it has been very effective, it can also cause side effects like inflammation, neurological issues, and low blood counts. Infections are already known to be a major concern with this treatment, but fungal infections—though serious—are not as well studied.
This study reviewed the records of 234 people treated with BCMA CAR T-cell therapy at two cancer centers between 2016 and 2023. Most patients had already received many rounds of treatment before getting CAR T-cell therapy. The researchers followed patients for one year to see how many developed invasive fungal disease (IFD), which means a fungal infection that spreads beyond the surface and can be life-threatening.
They found that only 4 patients, or about 1.7%, developed proven or probable fungal infections within a year of their CAR T-cell infusion. These included one case of Candida peritonitis and three cases of invasive aspergillosis. All four of these patients had severe treatment-related side effects, needed strong immune-suppressing drugs like steroids, and developed infections within the first 100 days after therapy. Two patients recovered, but two died with fungal infections alongside other complications.
The results suggest that while fungal infections can be very serious, they are relatively rare in people receiving BCMA CAR T-cell therapy. The biggest risk seems to be in patients who develop strong immune-related side effects that require heavy steroid treatment. Because of the low overall infection rate, the researchers concluded that routine antifungal prevention for all patients may not be necessary. Instead, they recommend a more personalized approach, focusing preventive treatment on patients at highest risk, especially in the first few months after infusion.
Even though fungal infections were uncommon, the authors stressed that doctors should stay alert for them. Early diagnosis and treatment remain important, since these infections can be deadly, particularly in patients who are already very sick from both their cancer and treatment side effects
"Single-cell proteomic analysis reveals Multiple Myeloma heterogeneity and the dynamics of the tumor immune microenvironment in precursor and advanced states"
Source
Mohamed Kamal, Stephanie N. Shishido, Jeremy Mason, Krina Patel, Elisabet E. Manasanch, Robert Z. Orlowski, Peter Kuhn, Single-cell proteomic analysis reveals Multiple Myeloma heterogeneity and the dynamics of the tumor immune microenvironment in precursor and advanced states, Neoplasia, Volume 66, 2025, 101189, ISSN 1476-5586, https://doi.org/10.1016/j.neo.2025.101189. August 2025.
Overview
Multiple myeloma is a cancer that begins in plasma cells, a type of blood cell found in the bone marrow. It often develops from earlier conditions called MGUS and smoldering myeloma (SMM). While treatments for multiple myeloma have improved over the years, the disease is still considered incurable. This makes it important for doctors to better understand how the disease develops and how to detect it earlier.
In this study, researchers looked closely at bone marrow samples from 22 patients at different stages of disease, as well as healthy controls. Using a highly detailed lab technique, they were able to study both the plasma cells and the surrounding immune cells that make up the bone marrow environment.
They found that as multiple myeloma progresses, the makeup of plasma cells changes. In early disease stages, plasma cells often carry markers called CD45 and have lower levels of CD138. But in advanced myeloma, plasma cells lose CD45 and show much higher levels of CD138. This shift points to changes in the cancer cells themselves as the disease becomes more aggressive.
The researchers also saw changes in the immune cells within the bone marrow. In patients with myeloma, there were fewer monocytes, macrophages, and lymphoid cells compared to healthy individuals. This suggests that the cancer may weaken the immune system in ways that help it grow and spread.
One plasma cell subgroup stood out. Found more often in newly diagnosed and relapsed myeloma, this group had high levels of BCMA and CD138—proteins that are already being studied as treatment targets. This finding could help guide the development of more effective, targeted therapies in the future.
Overall, this study provides new insights into how multiple myeloma evolves and interacts with the immune system. By identifying specific cell changes tied to disease progression, it may pave the way for better ways to predict risk and create new treatment strategies.
"Phase 2 trial of daratumumab, cyclophosphamide, thalidomide, and dexamethasone in newly diagnosed multiple myeloma"
Source
Edvan de Queiroz Crusoé, Joanna Suzana Leal Ribeiro dos Santos, Juliana de Andrade Santos, Herbert Henrique de Melo Santos, Allan de Souza Santos, Larissa Ferreira Lucas, Cristiane Almeida Requião de Pinna, Paula Nogueira Caldas Freire, Adriano Araujo de Jesus, Alessandro de Moura Almeida, Daniela Dourado Dutra, Marcos Fonseca Chaves, Jamile Souza Nicanor, Marco Aurelio Salvino, Maria da Gloria Bomfim Arruda, Vania Hungria; on behalf of GBRAM, Phase 2 trial of daratumumab, cyclophosphamide, thalidomide, and dexamethasone in newly diagnosed multiple myeloma. Blood Neoplasia 2025; 2 (3): 100081. doi: https://doi.org/10.1016/j.bneo.2025.100081 August 20, 2025.
Overview
This study looked at a treatment combination for people newly diagnosed with multiple myeloma who are eligible for an autologous stem cell transplant (ASCT). The regimen included Darzalex® (daratumumab), Cytoxan® (cyclophosphamide), Thalomid® (thalidomide), and dexamethasone—together called Dara-CTD. Patients first received four cycles of this combination, followed by a stem cell transplant. After transplant, they had four cycles of daratumumab plus thalidomide and dexamethasone, and then continued on daratumumab alone until their disease progressed or side effects became too difficult.
The main goal was to see how many patients achieved at least a “very good partial response” (VGPR), meaning the disease was reduced by at least 90%, after the second consolidation phase. Out of 24 patients, three achieved a complete response and 15 reached a VGPR, for a total response rate of 75%. These responses lasted from about 9 months to nearly 42 months, and the median duration had not yet been reached at the time of analysis. At three years, 65% of patients had not seen their cancer progress, and at four years, 70% were still alive.
Side effects were mostly manageable, though some patients did experience constipation, low white blood cell counts, fever with infection, nerve problems, or mouth sores. Seven patients developed COVID-19 during the trial, and two died from it. Two patients had to stop treatment completely because of side effects—one from cyclophosphamide and one from daratumumab.
Overall, the Dara-CTD regimen proved to be active and effective, offering strong responses with a safety profile that researchers considered acceptable. Importantly, it does not include a proteasome inhibitor, which is part of many current standard regimens. This makes Dara-CTD a potential alternative option for transplant-eligible patients with newly diagnosed multiple myeloma.
"Ambroxol induces myeloma cell death by inhibiting autophagy"
Source
Yutaka Hattori, Hiromu Sugiyama, Yamato Miyashita, Shinsuke Shibata, Taiga Okaue, Yoshinao Matsumoto, Taketo Yamada, Tomofumi Yamamoto, Takashi Yamaguchi, Kohei Yamazaki, Hisako Kunieda, Hideyuki Saya, Maiko Matsushita; Ambroxol induces myeloma cell death by inhibiting autophagy. Blood Neoplasia 2025; 2 (3): 100100. doi: https://doi.org/10.1016/j.bneo.2025.100100 August 20, 2025.
Overview
Over the past 10 years, new treatments have helped people with multiple myeloma live longer. Still, most patients eventually relapse, and some treatments cause serious side effects that can limit how long patients can stay on them. Researchers are continuing to search for new drugs that can both fight the disease and reduce treatment-related side effects.
In this study, scientists tested ambroxol hydrochloride (ambroxol), a drug already used for other purposes, to see if it could work against myeloma. They found that ambroxol was able to trigger cancer cell death by interfering with a process called autophagy. Autophagy is a way cells recycle their parts to survive under stress. By blocking the later stages of this process, ambroxol caused myeloma cells to build up waste inside them, which made it harder for the cells to survive.
The team then looked at how ambroxol might work with other myeloma drugs. One drug, panobinostat, actually increases autophagy in cancer cells. When ambroxol was combined with panobinostat, the two drugs worked together more strongly, killing more myeloma cells than either drug alone. In lab and animal models, ambroxol slowed tumor growth on its own and made panobinostat even more effective when given together. Surprisingly, it also helped reduce diarrhea, a common side effect of panobinostat.
These findings suggest that targeting autophagy could be a new way to treat multiple myeloma. Ambroxol, especially when paired with panobinostat, shows promise as a potential therapy that could not only improve effectiveness but also reduce treatment side effects. More research will be needed, but this study highlights a possible new direction for myeloma care.
"A novel cereblon variant with both exon 8 and 10 deletions in newly diagnosed and relapsed multiple myeloma"
Source
Yuan Xiao Zhu, Soumya Dutta, Gregory J. Ahmann, Laura Bruins, Mariano Arribas, Xianfeng Chen, Abhigna Polavarapu, Jonathan Chapman, Isaac Lopez, Marta Chesi, P. Leif Bergsagel, Abhishek Singharoy, Rafael Fonseca, Lisa M. Rimsza; A novel cereblon variant with both exon 8 and 10 deletions in newly diagnosed and relapsed multiple myeloma. Blood Neoplasia 2025; 2 (3): 100099. doi: https://doi.org/10.1016/j.bneo.2025.100099 August 20, 2025.
Overview
One of the biggest challenges in treating multiple myeloma is drug resistance—when the cancer stops responding to medicines that once worked. A common type of drug used in myeloma is called an immunomodulatory drug (IMiD). These drugs work by binding to a protein called cereblon (CRBN), which helps trigger the death of myeloma cells. But changes in the CRBN gene can make these drugs less effective over time.
In this study, researchers focused on a specific change in the CRBN gene called an exon 10 deletion. They created a new test that can detect this change and studied 74 myeloma samples—28 from newly diagnosed patients and 46 from patients with relapsed or advanced disease. They found that a few patients had high levels of exon 10 deletion, including one newly diagnosed patient and several whose disease had already relapsed.
Surprisingly, in some cases the gene had not only lost exon 10 but also exon 8. When researchers studied the effects of these deletions, they saw that the CRBN protein no longer functioned properly. This meant it could not interact the right way with the cellular machinery needed for IMiDs to work, contributing to drug resistance.
These results show that gene changes linked to drug resistance can appear even at the time of diagnosis, not just after years of treatment. Detecting these changes early may help doctors better understand why some patients respond to IMiDs while others do not, and could eventually guide more personalized treatment strategies.
"Belantamab mafodotin in patients with relapsed/refractory multiple myeloma: a real-world experience"
Source
Malin Hultcrantz, Andriy Derkach, Hani Hassoun, Neha Korde, Kylee Maclachlan, Sham Mailankody, Dhwani Patel, Urvi A. Shah, Carlyn R. Tan, David J. Chung, Oscar B. Lahoud, Heather J. Landau, Michael Scordo, Gunjan L. Shah, David Nemirovsky, Ross S. Firestone, Theresia Akhlaghi, Tala Shekarkhand, Sergio A. Giralt, Alexander M. Lesokhin, Saad Z. Usmani; Belantamab mafodotin in patients with relapsed/refractory multiple myeloma: a real-world experience. Blood Neoplasia 2025; 2 (3): 100103. doi: https://doi.org/10.1016/j.bneo.2025.100103 August 20, 2025
Overview
Blenrep (belantamab mafodotin) is a targeted treatment for multiple myeloma that works by attaching to BCMA, a protein found on myeloma cells, and delivering a cancer-killing drug directly to them. While earlier clinical trials showed its effectiveness, this study looked at how the drug performed in real-world use at Memorial Sloan Kettering Cancer Center between 2020 and 2023.
The study included 94 patients, most of whom had aggressive disease and had already received many other treatments—a median of six prior therapies. More than three-quarters of patients were “triple-class refractory,” meaning their disease no longer responded to the three main drug types used in myeloma. Some had even been treated with other BCMA-targeted therapies before starting belantamab.
Despite these challenges, belantamab produced meaningful results. The overall response rate was 43%, with about 1 in 5 patients achieving a very good partial response or better. For patients who had already tried other BCMA therapies, responses were lower but still present. On average, patients went about 3.8 months before their disease progressed, and those who responded stayed in remission for about 10.5 months. The median overall survival was more than 17 months, even in this heavily pretreated group.
The most common side effect was eye-related toxicity, seen in about two-thirds of patients. Around 15% had more severe changes in the cornea (keratopathy), but importantly, these effects were reversible and improved with dose adjustments or longer breaks between treatments. Infections occurred in some patients but were generally mild, and the overall risk of serious infections was low.
This real-world study showed that belantamab mafodotin can provide meaningful benefit to patients with advanced multiple myeloma, even after many prior therapies. While eye-related side effects are common, they can usually be managed with dose changes, allowing patients to continue treatment and maintain their response.
"DNA damage repair (DDR) related prognostic risk model in multiple myeloma based on single-cell and bulk sequencing"
Source
Hongxiu Liu, Zhihua Li, Yihua Wang, Can Li, Kaiqing Yan, Yanping Ma, DNA damage repair (DDR) related prognostic risk model in multiple myeloma based on single-cell and bulk sequencing, DNA Repair, Volume 152, 2025, 103857, ISSN 1568-7864, https://doi.org/10.1016/j.dnarep.2025.103857. August 2025.
Overview
Multiple myeloma is often marked by unstable DNA and rearrangements in the genetic code of cancer cells. These changes are thought to play an important role in how the disease grows and resists treatment, but the exact causes and impact of this DNA damage are not fully understood.
In this study, researchers analyzed genes involved in DNA damage repair (DDR) using both single-cell and bulk RNA sequencing data. They developed a model to see how DDR activity might relate to patient outcomes. The results showed that patients with higher levels of DDR gene activity tended to have worse outcomes than those with lower levels. The model was able to reliably predict prognosis across different patient groups.
The team also compared the immune system environment and genetic mutations between patients with low and high DDR activity. They identified three key DDR-related genes—PARP1, PCNA, and RAD23A—that may play a central role in myeloma progression. Further testing suggested that these genes could also influence how patients respond to certain drugs.
This research suggests that DDR genes could serve as useful biomarkers for predicting outcomes in multiple myeloma. Understanding a patient’s DDR profile might help doctors better assess risk, guide treatment choices, and even open the door to new targeted therapies in the future.
"Fresh and cryopreserved stem cell transplantation in myeloma patients: Does it make a difference on transplant outcomes?"
Source
Erkurt, Mehmet Ali et al. Fresh and cryopreserved stem cell transplantation in myeloma patients: Does it make a difference on transplant outcomes? Transfusion and Apheresis Science, Volume 64, Issue 4, 104184. August 2025.
Overview
When multiple myeloma patients are eligible for a stem cell transplant, they typically receive 4 to 6 cycles of treatment to prepare their body, followed by an autologous stem cell transplant. This type of transplant uses the patient's own stem cells rather than cells from a donor.
The transplant process involves several key steps. First, doctors help move stem cells from the bone marrow into the bloodstream and then collect these cells. Next, patients receive high-dose chemotherapy to destroy cancer cells. Finally, the collected stem cells are given back to the patient through an IV to help rebuild their blood and immune system.
An important question for doctors and patients is timing. The collected stem cells can either be given back to the patient fresh within 24 to 48 hours after collection, or they can be frozen and stored for future use. Researchers wanted to understand if one approach works better than the other.
To find answers, doctors studied 88 multiple myeloma patients who had stem cell transplants. Of these patients, 43 received frozen stem cells and 45 received fresh stem cells. About 60% of the patients were men and 40% were women. The researchers found that patient characteristics were similar between both groups before treatment began.
The study revealed interesting differences in recovery times. Patients who received fresh stem cells saw their white blood cell counts return to normal faster, taking about 10 days compared to 12 days for those who received frozen cells. However, patients who received frozen stem cells had their platelet counts recover more quickly, taking 11 days compared to 12 days for the fresh stem cell group.
Most importantly, all patients in the study successfully had their blood cells grow back and function properly, regardless of whether they received fresh or frozen stem cells. This means both approaches are safe and effective options for multiple myeloma patients undergoing stem cell transplants. The small differences in recovery times between the two methods are not significant enough to clearly favor one approach over the other.
"Blood-derived cell-free DNA is a superior biomarker for noninvasive DNA methylation profiling in multiple myeloma"
Source
Robbe Heestermans, Catharina Olsen, Shervine Ameli, Jana Succari, Toon Janssen, Wouter De Brouwer, Ann De Becker, Isabelle Vande Broek, Marleen Bakkus, Rik Schots, Elke De Bruyne, Ivan Van Riet; Blood-derived cell-free DNA is a superior biomarker for noninvasive DNA methylation profiling in multiple myeloma. Blood Adv 2025; 9 (16): 4306–4310. doi: https://doi.org/10.1182/bloodadvances.2025016480 August 26, 2025.
Overview
Multiple myeloma is a complex cancer that changes over time, developing new genetic patterns that can make it harder to treat. Scientists have discovered that certain chemical changes in DNA, called methylation, can turn off important genes that normally help fight cancer. When these protective genes get turned off, patients may not respond as well to common multiple myeloma treatments like immunomodulatory drugs, proteasome inhibitors, and newer therapies.
Understanding these DNA changes could help doctors choose better treatments for each patient. However, studying these changes has been challenging because it typically requires taking samples directly from the bone marrow through a painful procedure. Bone marrow biopsies are invasive and may not capture the full picture of what's happening throughout the body, since cancer can vary from one area to another.
Researchers are now exploring whether they can get the same important information through simple blood tests instead of bone marrow biopsies. These "liquid biopsies" look for cancer DNA that circulates in the bloodstream. Scientists can examine different types of DNA found in blood, including cell-free DNA that floats freely, DNA from circulating tumor cells, and DNA from immune cells.
In a recent study, researchers compared DNA methylation patterns from blood samples with those from bone marrow samples in 11 patients with relapsed multiple myeloma. They wanted to see if blood tests could provide the same valuable information as the more invasive bone marrow procedure. The study included both men and women with an average age of 72 years who had received an average of two previous treatments.
The results were promising. Cell-free DNA from blood samples was able to detect about 86% of the DNA methylation changes found across all patients in the study. When compared directly to bone marrow samples, blood-based cell-free DNA matched about 78% of the changes found in bone marrow. This was significantly better than other types of blood-based DNA testing, which only matched 42% to 53% of bone marrow findings.
Interestingly, the blood tests also revealed DNA changes that weren't found in the bone marrow samples. This suggests that blood testing might actually provide a more complete picture of what's happening throughout the body, since bone marrow biopsies only sample one small area.
The researchers also analyzed which biological pathways were affected by these DNA changes. They found that important cancer-related pathways were involved, including those that control cell growth, immune responses, and the structures that surround cells. Some of these pathways are already known to play important roles in multiple myeloma development and treatment resistance.
This research suggests that simple blood tests could replace invasive bone marrow biopsies for understanding the genetic changes in multiple myeloma. Blood testing is easier for patients, can be repeated more often, and may provide more comprehensive information about the disease. As this technology develops further, it could help doctors personalize treatments more effectively and monitor how well therapies are working without requiring painful procedures.
This approach represents an important step toward more personalized medicine for multiple myeloma patients, where treatment decisions are based on each person's unique genetic patterns rather than a one-size-fits-all approach.