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 December 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 December 2025)

"Impact of body mass index on anti-BCMA chimeric antigen receptor T-cell therapy outcomes in multiple myeloma"

Source

Ruth Choa, Kevin Miller, Advait Joshi, Cole Minsky, Samuel S. Han, Alexis Barselau, Andrew Yee, Andrew Branagan, Benjamin Puliafito, Matthew Frigault, Noopur Raje, Diana Cirstea; Impact of body mass index on anti-BCMA chimeric antigen receptor T-cell therapy outcomes in multiple myeloma. Blood Immunology & Cellular Therapy 2025; 1 (3): 100015. doi: https://doi.org/10.1016/j.bict.2025.100015 December 1, 2025. 

Overview

This retrospective study of patients with relapsed/refractory multiple myeloma treated with anti-BCMA CAR T-cell therapy found a nonlinear, U-shaped relationship between body mass index and outcomes. Patients who were overweight had significantly worse progression-free and overall survival than those with normal weight or obesity, while toxicity rates were similar across BMI groups, highlighting BMI as a potential host factor influencing CAR T efficacy.
 

"Evaluation of iMS-IP assay for the detection and typing of monoclonal immunoglobulins"

Source

Yu Chen, Liangshun You, Li Zhu, Xuejiao Yin, Qiumei Yao, Shengnan Ding, Jiaying Ge, Yi Liu, Hongyan Tong, Jie Jin, Haitao Meng, Min Yang, Evaluation of iMS-IP assay for the detection and typing of monoclonal immunoglobulins, Clinica Chimica Acta, 2025, 120756, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2025.120756. December 1, 2025.  

Overview

This study evaluated a mass spectrometry–based immunoglobulin MS–immunoprecipitation (iMS-IP) assay for detecting M-proteins in multiple myeloma and found it to be highly concordant with immunofixation electrophoresis but markedly more sensitive. The assay detected very low-level and non-secretory disease and more accurately distinguished therapeutic monoclonal antibodies, supporting its potential role in M-protein monitoring and peripheral blood MRD assessment pending further validation.

"Comprehensive evaluation of disease characteristics and outcomes of patients with extramedullary multiple myeloma in the modern era"

Source

Broughton M, Bhatta S, Sonali D, Bumma N, Khan AM, Devarakonda S, Umyarova E, Benson D, Rosko A, Cottini F. Comprehensive evaluation of disease characteristics and outcomes of patients with extramedullary multiple myeloma in the modern era. Haematologica 2025;110(12):3053-3064; https://doi.org/10.3324/haematol.2025.287545.  December 1, 2025. 

Overview

This single-institution analysis of 201 patients with extramedullary manifestations of multiple myeloma shows that prognosis varies substantially by disease context. While extramedullary disease at diagnosis or solitary plasmacytoma progressing to myeloma had outcomes similar to myeloma alone, primary or secondary plasma cell leukemia and extramedullary disease developing later in the disease course were associated with markedly inferior survival, underscoring the need for improved therapeutic strategies in these high-risk settings.

"Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma"

Source

Portuguese AJ, Liang EC, Huang JJ, Jeon Y, Dima D, Banerjee R, Kwok M, Cicero KI, Hirayama AV, Basom R, Khouderchah C, Shadman M, Fong L, Cowan AJ, Gauthier J. Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma. Haematologica 2025;110(12):3065-3077; https://doi.org/10.3324/haematol.2025.287985.  December 1, 2025. 

Overview

This retrospective study shows that active extramedullary disease in multiple myeloma is associated with significantly higher toxicity, including severe neurotoxicity, prolonged cytopenias, and increased infections, in patients treated with BCMA-directed CAR T therapy. Patients with extramedullary disease also had markedly lower response rates and substantially shorter progression-free and overall survival, confirming EMD as a major adverse prognostic factor in the CAR T setting.

"A plain language summary of patient preferences for treatments for multiple myeloma that has relapsed or is refractory to prior therapy"

Source

Ailawadhi, S., J. Inocencio, T., Mansfield, C., Chintakayala, P., Bussberg, C., Chi, L., … Ma, Q. (2025). A plain language summary of patient preferences for treatments for multiple myeloma that has relapsed or is refractory to prior therapy. Future Oncology, 1–11. https://doi.org/10.1080/14796694.2025.2584284  December 1, 2025. 

Overview

This study used an online survey to measure which treatment features matter most to patients with relapsed or refractory multiple myeloma, with the goal of informing shared treatment decisions. Patients prioritized longer survival above all else and were generally willing to accept higher infection risk and favored immediately available treatments if these offered meaningful survival benefit.

"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; 1 (3): 100024. doi: https://doi.org/10.1016/j.bglo.2025.100024  December 1, 2025. 

Overview

This study found that autologous stem cell transplantation significantly improved treatment responses and led to a median progression-free survival of about 3.5 years and overall survival of nearly 8 years in newly diagnosed multiple myeloma patients treated in Jordan. However, limited access to maintenance therapy and newer drugs highlights ongoing gaps in care in resource-limited settings.

"Paeoniflorin inhibits angiogenesis in multiple myeloma by decreasing the MEF2A level to downregulate the expression of lncRNA MALAT1 within exosomes"

Source

Fu, J., Wang, J., Zhang, J. et al. Paeoniflorin inhibits angiogenesis in multiple myeloma by decreasing the MEF2A level to downregulate the expression of lncRNA MALAT1 within exosomes. Sci Rep (2025). https://doi.org/10.1038/s41598-025-30101-6  December 1, 2025. 

Overview

This study found that myeloma cells promote tumor blood vessel growth by releasing exosomes carrying the RNA molecule MALAT1, which stimulates angiogenesis through increased VEGFA signaling and is linked to poorer outcomes in multiple myeloma. The natural compound paeoniflorin was shown to block this process by disrupting the MEF2A–MALAT1 pathway, reducing angiogenesis and tumor growth in laboratory and animal models.

"No overall survival benefit to adding venetoclax for patients with RRMM"

Source

Lawrence, L. (2025), No overall survival benefit to adding venetoclax for patients with RRMM. Cancer, 131: e70136. https://doi.org/10.1002/cncr.70136  December 2, 2025. 

Overview

This phase 3 study found that adding venetoclax to bortezomib and dexamethasone did not improve overall survival for all patients with relapsed or refractory multiple myeloma and was harmful in those without the t(11;14) genetic change. However, patients with t(11;14) or high BCL2 expression had much longer time before disease progression, supporting the selective, off-label use of venetoclax in this subgroup only.

"mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow"

Source

Taylor Fulton-Ward, Nancy Gudgeon, Isaac Thirlwell, Emma L. Bishop, Bryan Marzullo, Hannah Giles, Graham McIlroy, Paul Ferguson, Bhuvan Kishore, Kate Rogers, Nuri Alfasi, Timothy Wong, Satnam Aytain, Daniel A. Tennant, Guy Pratt, Sarah Dimeloe; mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow. Blood Adv 2025; 9 (23): 6175–6188. doi: https://doi.org/10.1182/bloodadvances.2025016439  December 2, 2025. 

Overview

This study found that low-oxygen conditions in the bone marrow weaken key CD8+ T-cell functions needed for immunotherapies in multiple myeloma, such as activation, growth, and immune signaling, even though initial tumor killing remains intact. These effects help explain why T-cell–based treatments may work less well in the bone marrow and point to hypoxia as an important barrier to improving immunotherapy outcomes.

"The Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Current Research in Translational Medicine"

Source

Turkan Aliyeva, Haroon Alamy, Feras Ahmad Ahmad, Julia Natche, Hafiza Khadija Shahid, Vrushali Shelar, Huu Than Huynh, Imane El-Amri, The Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Current Research in Translational Medicine, 2025,103559, ISSN 2452-3186, https://doi.org/10.1016/j.retram.2025.103559. December 2, 2025.  

Overview

This analysis found that adding anti-CD38 monoclonal antibodies to standard treatment significantly improves overall survival and progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo a transplant. Benefits were seen in both frail and non-frail patients, supporting the use of anti-CD38 therapy as part of frontline care for this vulnerable group.

"Enhanced Detection of Multiple Myeloma Cells by Next-Generation Flow Cytometry Following Density Gradient Medium Separation"

Source

A. O'Brien, V. Mykytiv, and F. O'Halloran, “Enhanced Detection of Multiple Myeloma Cells by Next-Generation Flow Cytometry Following Density Gradient Medium Separation,” European Journal of Haematology (2025): 1–11, https://doi.org/10.1111/ejh.70076.  December 2, 2025. 

Overview

This study found that using density gradient medium (DGM) for pre-enrichment improves measurable residual disease (MRD) detection in multiple myeloma by allowing larger blood or bone marrow samples to be processed, increasing sensitivity, and reducing processing time and costs. DGM was more effective and practical than other methods, supporting its use in clinical MRD testing.

"Distinct immunophenotypic profiles of circulating tumor plasma cells in MGUS and smoldering multiple myeloma"

Source

Uehara, A., Narita, K., Fujii, F. et al. Distinct immunophenotypic profiles of circulating tumor plasma cells in MGUS and smoldering multiple myeloma. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04117-7  December 2, 2025. 

Overview

This study found that circulating tumor plasma cells (CTPCs) in patients with MGUS and smoldering multiple myeloma (SMM) have distinct phenotypic and cytogenetic features compared with bone marrow plasma cells. CTPCs showed altered expression of surface markers and were associated with a higher prevalence of certain high-risk chromosomal abnormalities, providing insights into their biology and potential role in disease progression.

"Real-world outcomes of patients with relapsed refractory multiple myeloma treated with commercial bispecific T-cell engager antibodies: a single center experience"

Source

Fogel, L., Roney, P. C., Ahn, J., Aleman, A., Perez-Manon, F., Arias-Orozco, N., … Biran, N. (2025). Real-world outcomes of patients with relapsed refractory multiple myeloma treated with commercial bispecific T-cell engager antibodies: a single center experience. Leukemia & Lymphoma, 1–11. https://doi.org/10.1080/10428194.2025.2592783  December 2, 2025. 

Overview

This study evaluated real-world outcomes of 79 patients with relapsed/refractory multiple myeloma treated with T-cell engagers (teclistamab, talquetamab, or elranatamab). Although the overall response rate was similar to clinical trials (64%), progression-free and overall survival were shorter, highlighting the need for earlier use of TCEs and improved access for patients with lower income or other socioeconomic barriers.

"Characterizing circulating rare cells in peripheral blood for detecting and monitoring multiple myeloma and precursor states"

Source

Shishido, S.N., Mason, J., Kamal, M. et al. Characterizing circulating rare cells in peripheral blood for detecting and monitoring multiple myeloma and precursor states. npj Precis. Onc. 9, 388 (2025). https://doi.org/10.1038/s41698-025-01175-2  December 2, 2025. 

Overview

This study used a liquid biopsy approach to detect and profile circulating plasma cells in 68 patients across MGUS, SMM, newly diagnosed, and relapsed/refractory multiple myeloma. Distinct phenotypic subpopulations, particularly the D | CD138 | BCMA-Memb phenotype, increased with disease progression, enabling differentiation of precursor from overt MM with 86% accuracy and highlighting the potential of blood-based monitoring for disease detection and progression.

"Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials"

Source

Khan A, Rahman M, Jawed I, et al. (December 03, 2025) Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials. Cureus 17(12): e98368. doi:10.7759/cureus.98368  December 3, 2025. 

Overview

This study systematically reviewed clinical trials evaluating anti-BCMA bispecific antibodies in relapsed/refractory multiple myeloma (RRMM). Across 11 trials including 910 heavily pretreated patients, these therapies showed overall response rates of 40–78% depending on the agent and prior treatment exposure, with mostly low-grade, manageable toxicities such as cytokine release syndrome and hematologic effects, supporting BCMA-targeted bispecifics as a promising new treatment option for advanced RRMM.

"AI-derived five-gene signature predicts risk in multiple myeloma under bortezomib-based therapy"

Source

Gargano, G., Pappagallo, S.A., Quinto, A.M. et al. AI-derived five-gene signature predicts risk in multiple myeloma under bortezomib-based therapy. Sci Rep (2025). https://doi.org/10.1038/s41598-025-30527-y  December 3, 2025. 

Overview

This study developed a prognostic model for multiple myeloma (MM) based on gene expression in the bone marrow tumor microenvironment rather than tumor cells. The MM-5C model, incorporating five genes (SOX11, METTL11B, C3, RBM10, HOMEZ), effectively stratifies patients receiving bortezomib-based therapy into distinct risk groups, independently of traditional staging, highlighting the importance of the microenvironment in predicting outcomes and guiding personalized treatment.

"Piwi-interacting RNA-823 promotes cell growth and chemoresistance by stimulating the TGF-β1-mediated AKT/ERK pathway in multiple myeloma"

Source

Wei Wei, Dongjiao Wang, Nian Zhou, Haimin Chen, Wenjun Yu, Lixia Wu, Rong Peng, Haotian Shi, Fan Zhou, Piwi-interacting RNA-823 promotes cell growth and chemoresistance by stimulating the TGF-β1-mediated AKT/ERK pathway in multiple myeloma, International Immunopharmacology, Volume 166, 2025, 115405, ISSN 1567-5769, https://doi.org/10.1016/j.intimp.2025.115405. December 3, 2025. 

Overview

This study investigated the role of piRNA-823 in multiple myeloma (MM) and found that it is elevated in newly diagnosed and relapsed/refractory patients. In cell experiments, piRNA-823 promoted MM cell proliferation and chemoresistance while inhibiting apoptosis by activating the TGF-β1-mediated AKT/ERK signaling pathway, suggesting that targeting piRNA-823 could help overcome drug resistance in MM.

"Outcomes of elranatamab in relapsed/refractory multiple myeloma: prognostic impact of monocyte count"

Source

Kikuchi, T., Sugita, S., Kondo, U. et al. Outcomes of elranatamab in relapsed/refractory multiple myeloma: prognostic impact of monocyte count, MyCARe, and R2-ISS. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04127-5  December 3, 2025. 

Overview

This study evaluated real-world outcomes of elranatamab in 37 patients with relapsed/refractory multiple myeloma. The overall response rate was 68%, with 46% achieving at least a very good partial response, and one-year overall survival was 66%. Poor prognosis was associated with extramedullary disease, circulating plasma cells, high-risk cytogenetics, low baseline monocyte count, high modified MyCARe risk, and dynamic R2-ISS stage IV, highlighting potential practical prognostic markers.

"Determining a safe pre-transfusion protocol for multiple myeloma patients on anti-CD38 treatment."

Source

Nicolson A, Falconer J. Determining a safe pre-transfusion protocol for multiple myeloma patients on anti-CD38 treatment. Transfusion Medicine. 2025; 1-6. doi:10.1111/tme.70046  December 3, 2025. 

Overview

This study evaluated blood transfusion safety in multiple myeloma patients receiving daratumumab, which can interfere with antibody screening. Analysis of 102 transfused patients found no cases of alloimmunization, supporting the safety of NHS Lothian’s protocol of pre-treatment extended phenotyping and matched red cell transfusions, and suggesting that using sCD38 in pre-transfusion testing could further simplify procedures while maintaining safety.

"Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis"

Source

Voorhees, P.M., Kumar, S., Usmani, S.Z. et al. Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06705-3  December 3, 2025. 

Overview

This study pooled data from nine historical trials to evaluate outcomes of relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) versus those without. Patients with EMD had substantially worse outcomes, with a 21% overall response rate versus 66%, median progression-free survival of 6.3 versus 12.9 months, and median overall survival of 21 versus 39 months, even after adjusting for age, prior therapies, and disease stage, highlighting the urgent need for more effective treatments for this high-risk population.

"Immunotherapy in multiple myeloma: advances from immune microenvironment insights to clinical application"

Source

Zhang, Y., Lei, Y., Huang, Y. et al. Immunotherapy in multiple myeloma: advances from immune microenvironment insights to clinical application. Mol Biol Rep 53, 158 (2026). https://doi.org/10.1007/s11033-025-11317-1  December 3, 2025. 

Overview

This review highlights how the immune microenvironment in multiple myeloma (MM)—including dysfunctional dendritic cells, impaired NK cells, and immunosuppressive regulatory cells—promotes tumor immune evasion and limits immunotherapy effectiveness. Despite advances with monoclonal antibodies, CAR-T therapy, and bispecific antibodies, treatment variability, toxicity, and resistance remain challenges, underscoring the need for novel targets, gene-editing integration, and precision medicine approaches to improve outcomes.

"Final OS analyses from the TOURMALINE- MM3 and -MM4 RCTs of ixazomib maintenance in newly diagnosed multiple myeloma"

Source

Dimopoulos, M.A., Lonial, S., Chng, WJ. et al. Final OS analyses from the TOURMALINE- MM3 and -MM4 RCTs of ixazomib maintenance in newly diagnosed multiple myeloma. Blood Cancer J. (2025). https://doi.org/10.1038/s41408-025-01411-9  December 4, 2025. 

Overview

The final overall survival analyses of the phase 3 TOURMALINE-MM3 and -MM4 studies showed that fixed-duration ixazomib maintenance did not significantly improve OS compared with placebo in post-transplant or transplant-ineligible patients with newly diagnosed multiple myeloma, despite prior progression-free survival benefits. No new safety concerns were observed, highlighting that the availability of effective salvage therapies may limit the ability to demonstrate OS improvements in frontline myeloma trials.

"Belantamab mafodotin, lenalidomide and dexamethasone (BelaRd) in newly diagnosed intermediate-fit and frail myeloma"

Source

Evangelos Terpos, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Panos Malandrakis, Despina Fotiou, Nikolaos Kanellias, Magdalini Migkou, Foteini Theodorakakou, Vasiliki Spiliopoulou, Irene Solia, Evangelos Eleutherakis-Papaiakovou, Giorgos Psarros, Efstathios Kastritis, Meletios A Dimopoulos; Belantamab mafodotin, lenalidomide and dexamethasone (BelaRd) in newly diagnosed intermediate-fit and frail myeloma. Blood 2025; blood.2025031629. doi: https://doi.org/10.1182/blood.2025031629  December 4, 2025. 

Overview

The phase 1/2 BelaRd study showed that belantamab mafodotin combined with lenalidomide and dexamethasone is highly effective in unfit and frail, transplant-ineligible patients with newly diagnosed multiple myeloma, achieving an overall response rate of 97.6% and durable 18-month PFS and TTP rates of 83.0% and 97.2%, respectively. Ocular adverse events were manageable, minimally impacted quality of life, and the hematologist-led Vision-Related Anamnestic tool may reduce the need for ophthalmologist-led dosing assessments, supporting further evaluation in a phase 3 trial.

"MRD contamination in peripheral blood autologous stem cell grafts: implications for relapse and prognosis in multiple myeloma"

Source

Lin, J., He, J., Cai, Z., & He, D. (2025). MRD contamination in peripheral blood autologous stem cell grafts: implications for relapse and prognosis in multiple myeloma. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2596804  December 4, 2025. 

Overview

This study describes how measurable residual disease (MRD) in peripheral blood autologous stem cell grafts serves as a strong prognostic indicator in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). Detection of clonal plasma cells (CPCs) in grafts using flow cytometry, next-generation flow cytometry, or sequencing reflects pre-transplant tumor burden and is associated with shorter progression-free and overall survival, though it is not a direct cause of relapse. Incorporating graft MRD status into comprehensive risk assessments can guide preemptive, intensified, or maintenance therapies, and interventions such as ex vivo graft CPC clearance may benefit select high-risk patients, while continuous post-transplant MRD monitoring enhances dynamic patient management.

"A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma"

Source

Michael Rade, David Fandrei, Markus Kreuz, Sabine Seiffert, Anja Grahnert, Maik Friedrich, Thomas Wiemers, Patrick Born, Luise Fischer, Heike Weidner, Lorenz C. Hofbauer, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Jonathan Scolnick, Mirco Friedrich, Farid Keramati, Peter Brazda, Zsolt Sebestyen, Jürgen Kuball, Miriam Alb, Lukas Scheller, Michael Hudecek, Hermann Einsele, Klaus H. Metzeler, Marco Herling, Carmen Diana Herling, Madlen Jentzsch, Georg-Nikolaus Franke, Andreas Boldt, Ulrike Köhl, Uwe Platzbecker, Vladan Vucinic, Kristin Reiche, Maximilian Merz, A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma, Cancer Cell, 2025, ISSN 1535-6108,https://doi.org/10.1016/j.ccell.2025.10.014. December 4, 2025. 

Overview

This is a study of CAR T-cell therapies targeting BCMA in relapsed or refractory multiple myeloma (RRMM). In 61 patients treated with idecabtagene vicleucel (Ide-cel) or ciltacabtagene autoleucel (Cilta-cel), Cilta-cel achieved higher complete response rates (78% vs. 38%) and longer progression-free survival. Single-cell multi-omics analysis revealed that expansion of CD4+ cytotoxic T cells was linked to complete responses and immune-related toxicities, while non-responding CD8+ T cells showed impaired function. Plasmacytoid dendritic cells expressed high BCMA, suggesting a potential new therapeutic target, and reductions in soluble BCMA correlated with better CAR T expansion and systemic inflammation, illuminating mechanisms behind CAR T efficacy and toxicity.

"CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma"

Source

Danai Dima, Rahul Banerjee, Doris K. Hansen; CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma. Hematology Am Soc Hematol Educ Program 2025; 2025 (1): 324–333. doi: https://doi.org/10.1182/hematology.2025000721  December 5, 2025. 

Overview

This study reviews the impact of CAR T-cell therapy and bispecific antibodies in relapsed/refractory multiple myeloma (RRMM). Approved BCMA-targeted CAR T therapies, idecabtagene vicleucel and ciltacabtagene autoleucel, and four bispecific antibodies—including BCMA-targeted (teclistamab, elranatamab, linvoseltamab) and GPRC5D-targeted (talquetamab)—have shown strong efficacy with manageable toxicities. The review discusses integrating CAR T therapy earlier in treatment, the evolving role and safety of bispecific antibodies, practical patient selection and supportive care considerations, and strategies for sequencing these T-cell redirecting therapies to optimize long-term outcomes.

"How to approach the high-risk myeloma from induction through relapse?"

Source

Katja C. Weisel, Christoph Schaefers, Lisa B. Leypoldt; How to approach the high-risk myeloma from induction through relapse?. Hematology Am Soc Hematol Educ Program 2025; 2025 (1): 652–658. doi: https://doi.org/10.1182/hematology.2025000762 December 5, 2025. 

Overview

This study discusses the ongoing challenges in treating high-risk multiple myeloma (HRMM). HR disease is defined primarily by cytogenetic abnormalities, and early identification is critical for guiding optimal therapy. Evidence supports upfront quadruplet therapy, consolidation, and continuous combination maintenance. including high-dose melphalan and autologous stem cell transplantation—for eligible patients to achieve sustained minimal residual disease (MRD)–negative responses. Patients who relapse within 12–18 months despite optimal frontline therapy are considered functional HR and remain difficult to treat, but emerging B-cell maturation antigen (BCMA)–directed T-cell therapies, including CAR T cells, show promising durable responses in this setting.

"Comment je fais le suivi du myélome multiple en IRM corps entier ?, Journal d'imagerie diagnostique et interventionnelle"

Source

L. Redon, C. Hocine, U. Chamard-Champliaud, C. Cyteval, Comment je fais le suivi du myélome multiple en IRM corps entier ?, Journal d'imagerie diagnostique et interventionnelle, 2025, ISSN 2543-3431, https://doi.org/10.1016/j.jidi.2025.08.002. December 5, 2025. 

Overview

This study explains that whole-body MRI is a key tool for assessing and monitoring multiple myeloma. Standard imaging protocols include T1, STIR, Dixon, and diffusion sequences with ADC mapping to detect focal lesions and classify bone marrow patterns. The MY-RADS system standardizes image acquisition, interpretation, and reporting, using the RAC Score to evaluate treatment response, with increases in ADC values indicating a likely therapeutic response. Whole-body MRI combined with MY-RADS provides a reliable framework for monitoring disease progression and treatment efficacy in multiple myeloma patients.

"The real-world safety profile and potential mechanism of isatuximab: Integration of pharmacovigilance and transcriptomic analysis"

Source

Weng, Xiufang MDa; Ren, Yanfei MDb; Hao, Qingqing PhDc,*. The real-world safety profile and potential mechanism of isatuximab: Integration of pharmacovigilance and transcriptomic analysis. Medicine 104(49):p e45941, December 05, 2025. | DOI: 10.1097/MD.0000000000045941  December 5, 2025. 

Overview

This study evaluates the long-term safety of isatuximab in real-world multiple myeloma treatment. Using FDA adverse event reports and transcriptomic analyses, researchers identified known toxicities such as neutropenia, pneumonia, and kidney injury, as well as new signals including tumor lysis syndrome and hypoproteinemia. Molecular analysis suggested that CD38-driven immune and metabolic dysregulation may underlie these adverse events. These findings highlight the need for careful patient monitoring and personalized strategies to reduce treatment-related risks.

"Results of delayed or salvage autologous hematopoietic stem cell transplantation for multiple myeloma"

Source

Pasvolsky, O., Marcoux, C., Milton, D.R. et al. Results of delayed or salvage autologous hematopoietic stem cell transplantation for multiple myeloma. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02771-3  December 5, 2025. 

Overview

This study evaluates delayed or salvage autologous hematopoietic cell transplantation (autoHCT) in relapsed multiple myeloma. In 650 patients, median progression-free survival was 17.5 months and overall survival 47.3 months, with low early non-relapse mortality. Outcomes were better for salvage transplants performed ≥24 months after the first autoHCT. Factors such as high-risk cytogenetics, advanced R-ISS stage, refractory disease, and multiple prior therapy lines were linked to poorer outcomes, while achieving complete response post-transplant and receiving maintenance therapy improved survival. The study confirms that delayed or salvage autoHCT is feasible and effective, especially for patients with longer initial remissions.

"TRIP13 alters mitochondrial function and promotes bortezomib resistance in multiple myeloma"

Source

Chen, Y., Liu, Y., Wang, Y. et al. TRIP13 alters mitochondrial function and promotes bortezomib resistance in multiple myeloma. Sci Rep (2025). https://doi.org/10.1038/s41598-025-31265-x  December 6, 2025. 

Overview

This study explored the role of TRIP13 in bortezomib (BTZ) resistance in multiple myeloma. TRIP13 is upregulated in MM and linked to advanced disease and poorer survival. In cell studies, overexpression of TRIP13 increased proliferation, reduced BTZ-induced apoptosis, and preserved mitochondrial function by interacting with the mitochondrial calcium uniporter (MCU). These findings suggest that TRIP13 helps MM cells survive proteotoxic stress and contributes to BTZ resistance, identifying it as a potential therapeutic target to improve patient outcomes.

"Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis"

Source

Souto Filho, J.T.D., Cantadori, L.O., Crusoe, E.d.Q. et al. Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis. Blood Cancer J. 15, 212 (2025). https://doi.org/10.1038/s41408-025-01413-7 December 6, 2025. 

Overview

This study compares quadruplet versus triplet regimens for transplant-ineligible newly diagnosed multiple myeloma. Anti-CD38 monoclonal antibody-based quadruplets (D-VRd and I-VRd) significantly improved progression-free survival (PFS) and overall survival (OS) compared with triplets, with estimated 60-month OS rates of ~72% versus 67%. The analysis supports quadruplet regimens as the superior frontline therapy for this patient population.

"RedirecTT-1 Investigators Study Group. Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab"

Source

Kumar S, Mateos MV, Ye JC, Atrash S, Magen H, Quach H, Chu MP, Trudel S, Richter J, Rodríguez-Otero P, Chuah H, Gatt M, Medvedova E, Raza S, Yoon DH, Ishida T, Matous JV, Rosiñol L, Onodera K, Scott E, Heuck C, Zhang J, Henninger T, O'Rourke L, Thakkar P, Festa M, Huang L, Zhou J, Takamoto M, Pei L, Lu J, Au N, Krevvata M, Usmani SZ, Cohen YC; RedirecTT-1 Investigators Study Group. Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab. N Engl J Med. 2025 Dec 7. doi: 10.1056/NEJMoa2514752. Epub ahead of print. 

Overview

This study evaluates talquetamab plus teclistamab in patients with drug-resistant, true extramedullary multiple myeloma. Among 90 patients, 79% responded to treatment, with 64% maintaining response for ≥12 months; 12-month progression-free survival was 61% and overall survival was 74%. While most patients experienced adverse events—including cytokine release syndrome and hematologic toxicities—treatment discontinuation was rare, supporting the combination’s efficacy in this high-risk population.

"Evolution of Multiple Myeloma from a Genomic Perspective"

Source

Francesco Maura, Mehmet K. Samur, Nikhil C. Munshi; Evolution of Multiple Myeloma from a Genomic Perspective. Blood 2025; blood.2024026313. doi: https://doi.org/10.1182/blood.2024026313  December 8, 2025.  

Overview

This review describes how multiple myeloma (MM) develops from precursor conditions, including smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS). Disease progression is influenced by genetic predisposition, early genomic events, environmental exposures, and immune surveillance, with subclonal evolution driving transformation to symptomatic MM. Integrating genomic, transcriptomic, and immune profiling is essential to identify patients at high risk of progression and improve early disease prediction.

"Rapid identification and quantification of residual daratumumab in multiple myeloma patients by MALDI - TOF mass spectrometry"

Source

Hou-Long Luo, Huan Ding, Fan Chen, Yuxi Wang, Lin Zhou, Peng Ye, Hui Yu, Shangying Wu, Weiji Xie, Rui Ji, Jiatong Huang, Zhenping Su, Anping Xu, Ling Ji, Rapid identification and quantification of residual daratumumab in multiple myeloma patients by MALDI - TOF mass spectrometry, Clinica Chimica Acta, 2025,120775, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2025.120775. December 8, 2025. 

Overview

This study evaluated a mass spectrometry-based assay (iMS-LC) for distinguishing daratumumab from endogenous M-proteins in multiple myeloma patients receiving anti-CD38 therapy. The assay demonstrated high precision, sensitivity, and the ability to accurately differentiate daratumumab from M-proteins in most patients, providing a practical tool for monitoring treatment response when conventional electrophoretic methods are limited.

"Talquetamab-Related Dysgeusia in Multiple Myeloma Compared to BCMA-Targeted Bispecifics and High-Dose Melphalan"

Source

A. Fleischer, M. Roll, J. H. Frenking, et al., “Talquetamab-Related Dysgeusia in Multiple Myeloma Compared to BCMA-Targeted Bispecifics and High-Dose Melphalan,” Cancer Medicine 14, no. 23 (2025): e71401, https://doi.org/10.1002/cam4.71401.  December 8, 2025. 

Overview

This study evaluated taste disturbances (dysgeusia) in multiple myeloma patients receiving talquetamab (TAL), high-dose melphalan with autologous stem cell transplant (MEL/ASCT), or anti-BCMA bispecific antibodies. Results showed that TAL caused the most severe taste impairment, affecting quality of life and treatment adherence, highlighting the need for proactive monitoring and strategies to manage dysgeusia in patients receiving T-cell–engaging therapies.

"Uncovering the ultra-frail: A distinct subgroup in non-transplant eligible newly diagnosed patients with multiple myeloma, with an inferior clinical outcome"

Source

Groen, K., Smits, F., Nasserinejad, K., Levin, M.-D., Regelink, J.C., Timmers, G.-J., de Waal, E.G.M., Westerman, M., Velders, G.A., de Heer, K., Leys, R.B.L., van Kampen, R.J.W., Stege, C.A.M., Seefat, M.R., Nijhof, I.S., van der Spek, E., Klein, S.K., van de Donk, N.W.C.J., Ypma, P.F. and Zweegman, S. (2025), Uncovering the ultra-frail: A distinct subgroup in non-transplant eligible newly diagnosed patients with multiple myeloma, with an inferior clinical outcome. HemaSphere, 9: e70268. https://doi.org/10.1002/hem3.70268  December 8, 2025. 

Overview

This study examined non-transplant eligible, newly diagnosed multiple myeloma patients who were classified as frail using the IMWG Frailty Index, further stratifying them into three subgroups: frail-by-age, frail-by-impairments, and ultra-frail. Results showed that ultra-frail patients had the worst outcomes, with the shortest progression-free and overall survival, highest early mortality, and most frequent treatment discontinuation, highlighting that frailty subgroups are clinically heterogeneous and should be incorporated into treatment planning and future clinical trials to optimize outcomes.

"MajesTEC-3 Trial Investigators. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma"

Source

Costa LJ, Bahlis NJ, Perrot A, Nooka AK, Lu J, Pawlyn C, Mina R, Caeiro G, Kentos A, Hungria V, Reece D, Niu T, Mylin AK, Hansen CT, Teipel R, Besemer B, Dimopoulos MA, Zamagni E, Yoshihara S, Kim K, Min CK, Geerts P, Van Leeuwen-Segarceanu E, Tyczynska A, Reguera JL, Johansson M, Hansson M, Turgut M, Grey M, Sidana S, Rodriguez-Otero P, Martinez-Lopez J, Hashmi H, Carson R, Kobos R, Sun W, Lantz K, Seifert A, Briseno-Toomey D, O'Rourke L, Rubin M, Vieyra D, Kang L, Mateos MV; MajesTEC-3 Trial Investigators. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2514663. Epub ahead of print. 

Overview

This phase 3 study found that combining teclistamab with daratumumab significantly improved progression-free survival, overall response, complete response rates, and MRD negativity in patients with multiple myeloma who had received one to three prior therapies, compared to standard regimens with daratumumab plus pomalidomide or bortezomib. While serious adverse events were more frequent in the teclistamab–daratumumab group, the combination offers a highly effective treatment option for this patient population.

"Multi-omics profiling and AI-driven clinically deployable risk models in MGUS and smoldering myeloma"

Source

Wu, Y., Zhang, D., Jiang, J. et al. Multi-omics profiling and AI-driven clinically deployable risk models in MGUS and smoldering myeloma. Clin Exp Med (2025). https://doi.org/10.1007/s10238-025-01987-3 December 8, 2025. 

Overview

This study reviews the limitations of current risk models in predicting progression from MGUS and smoldering multiple myeloma to multiple myeloma and highlights how multi-omics technologies combined with AI and machine learning could improve individualized risk prediction. It also addresses the technical, ethical, and regulatory challenges of implementing these advanced tools in clinical practice, providing guidance for their future integration into patient care.

"Bispecific BAFF-R/BCMA CAR T cells control growth of heterogeneous plasma cells in multiple myeloma"

Source

Agnese Fiori, Karin Zimmermann, Anna Li, Jörg Westermann, Ioannis Anagnostopoulos, Lutz Menzel, Mario Bunse, Henry Erdlei, Jeyan Jayarajan, Florian Grünschläger, Juan Pablo Ortiz-Aguirre, Simon Haas, Uwe-Jens Teßmann, Jens Freitag, Andreas Rosenwald, Larry Kwak, Xiuli Wang, Zhenyuan Dong, Soungchul Cha, John Reiser, Eigen Peralta, Bahram Valamehr, Jan Krönke, Uta E. Höpken, Armin Rehm, Bispecific BAFF-R/BCMA CAR T cells control growth of heterogeneous plasma cells in multiple myeloma, Molecular Therapy, 2025, ISSN 1525-0016, https://doi.org/10.1016/j.ymthe.2025.12.005. December 9, 2025 

Overview

This study shows that targeting both BCMA and BAFF-R with bispecific CAR T cells may overcome the common problem of BCMA loss in relapsed or refractory multiple myeloma. Dual BAFF-R/BCMA CARs effectively killed myeloma cells in vitro and in vivo, prevented antigen escape, and offer a promising strategy to eliminate malignant plasma cells, including those with poor prognosis or early differentiation stages that lack BCMA.

"Longitudinal profiling of tumor and immune compartments uncovers patterns of dysregulation and associations with response in multiple myeloma"

Source

Denis J. Ohlstrom, William C. Pilcher, Marina E. Michaud, Chaitanya Acharya, Sarthak Satpathy, Edgar Gonzalez-Kozlova, Reyka G. Jayasinghe, Katherine Ferguson, Hope L. Mumme, Shivani Nanda, Yizhe Song, Sowmitri Mantrala, Dimitra Karagkouni, Jessica Schulman, Nick Pabustan, Junia Vieira Dos Santos, Daniel W. Sherbenou, Jonathan J. Keats, Alexander M. Gout, Steven Foltz, Alessandro Lagana, Taxiarchis Kourelis, Ravi Vij, Madhav V. Dhodapkar, David Avigan, Hearn Jay. Cho, Linda B. Baughn, Ajay K. Nooka, Sagar Lonial, Shaji Kumar, Mehmet K. Samur, Ioannis S. Vlachos, Li Ding, Sacha Gnjatic, George Mulligan, Manoj K. Bhasin; Longitudinal profiling of tumor and immune compartments uncovers patterns of dysregulation and associations with response in multiple myeloma. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0205  December 9, 2025. 

Overview

This study used multi-omics profiling to explore how immune cells influence multiple myeloma progression and treatment response. It found that recovery of naïve B cells is linked to longer progression-free survival, while disease progression involves T-cell exhaustion, B-cell depletion, and upregulation of cancer-testis antigens, which may serve as therapeutic targets in high-risk patients.

"PET Imaging of CD38 and IND enabling studies of [89Zr]Zr-DFO-Isatuximab"

Source

Wright, B.D., Houson, H.A., Fernandez, S. et al. PET Imaging of CD38 and IND enabling studies of [89Zr]Zr-DFO-Isatuximab. Mol Imaging Biol (2025). https://doi.org/10.1007/s11307-025-02062-9  December 9, 2025. 

Overview

This study used multi-omics profiling to explore how immune cells influence multiple myeloma progression and treatment response. It found that recovery of naïve B cells is linked to longer progression-free survival, while disease progression involves T-cell exhaustion, B-cell depletion, and upregulation of cancer-testis antigens, which may serve as therapeutic targets in high-risk patients.

"PET Imaging of CD38 and IND enabling studies of [89Zr]Zr-DFO-Isatuximab"

Source

Wright, B.D., Houson, H.A., Fernandez, S. et al. PET Imaging of CD38 and IND enabling studies of [89Zr]Zr-DFO-Isatuximab. Mol Imaging Biol (2025). https://doi.org/10.1007/s11307-025-02062-9  December 9, 2025. 

Overview

Researchers tested whether isatuximab, a drug that targets the CD38 protein on myeloma cells, could also be used as a PET scan tracer to help find myeloma in the body. They attached a small amount of a radioactive marker to isatuximab so it could be seen on imaging scans.

In lab studies and in mice with myeloma tumors, the tracer strongly attached to CD38-positive myeloma cells and clearly highlighted tumors on PET/CT scans. When CD38 levels were increased using certain myeloma drugs, the imaging signal also increased. Safety testing showed radiation doses similar to other approved PET tracers.

Overall, this imaging agent appears accurate, safe, and ready to be studied in people with multiple myeloma in future clinical trials.

"Risk of synchronous and second primary malignancies in transplant-ineligible patients with multiple myeloma treated with lenalidomide"

Source

Thomas Systchenko, Laly Nsiala, Arthur Bobin, Hélène Gardeney, Carine Motard, Gaelle Olivier, Florence Borde, Anne Corby, Christophe Roul, Emmanuel Fleck, Guillaume Denis, Céline Dieval, Philippe Mottaz, Annick Boscagli, Gautier Defossez, Xavier Leleu; Risk of synchronous and second primary malignancies in transplant-ineligible patients with multiple myeloma treated with lenalidomide. Blood Adv 2025; 9 (23): 6001–6008. doi: https://doi.org/10.1182/bloodadvances.2025016625  December 9, 2025. 

Overview

This study looked at the risk of developing other cancers in people with newly diagnosed multiple myeloma who were not eligible for transplant. The researchers focused on the difference between cancers found at the same time as myeloma diagnosis (called synchronous malignancies) and cancers that developed later (second primary malignancies).

They found that many additional cancers were discovered around the time myeloma was diagnosed, likely because patients undergo extensive testing such as full-body scans and bone marrow exams. These tests can uncover small or inactive cancers that might not have been found otherwise.

Importantly, patients treated with lenalidomide without certain chemotherapy drugs did not have a higher risk of developing new cancers later compared with the general population. These findings are reassuring but need confirmation with longer follow-up.

"Geriatric Nutritional Risk Index predicted survival time in multiple myeloma"

Source

Kazuhito Suzuki, Tadahiro Gunji, Riku Nagao, Masaharu Kawashima, Hideki Uryu, Mamiko Momoki, Hiroto Ishii, Ryoko Fukushima, Mitsuji Katori, Hiroki Yokoyama, Atsushi Katsube, Takeshi Saito, Kaichi Nishiwaki, Shingo Yano, Geriatric Nutritional Risk Index predicted survival time in multiple myeloma, Clinical Nutrition Open Science, 2025, ISSN 2667-2685, https://doi.org/10.1016/j.nutos.2025.12.003. December 10, 2025. 

Overview

This study examined whether a simple nutrition-related score, called the Geriatric Nutritional Risk Index (GNRI), can help predict survival in people with newly diagnosed multiple myeloma. GNRI is based on blood albumin levels and body weight, both markers of overall nutritional health.

Researchers found that nearly half of patients had a high nutrition risk at diagnosis, and these patients had shorter survival compared with those at lower risk. GNRI was a stronger predictor of survival than commonly used performance or frailty scores. Importantly, nutrition risk improved for many patients during treatment. Patients whose GNRI improved over the first year had survival similar to those who started at low risk.

Overall, monitoring and improving nutrition over time may play an important role in outcomes for people with multiple myeloma.

"Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study"

Source

Rakesh Popat et al. Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study. J Clin Oncol 0, JCO-25-00924 DOI:10.1200/JCO-25-00924  December 10, 2025.

Overview

This phase 3 study compared two treatment options for people with relapsed or refractory multiple myeloma who have the t(11;14) genetic change. One group received venetoclax plus dexamethasone, and the other received pomalidomide plus dexamethasone.

Patients treated with venetoclax and dexamethasone had higher response rates and deeper responses, including some patients with no detectable disease, compared with the pomalidomide group. Although the study did not meet its main goal of significantly improving the time before the disease worsened, patients on venetoclax tended to live longer and stay progression-free longer. Infections were more common with venetoclax, but no new safety concerns were identified.

"Reprogramming glutamine metabolism enhances BCMA-CAR T-cell fitness and therapeutic efficacy in multiple myeloma"

Source

Flor Navarro, Teresa Lozano, Andrea Fuentes-García, Inés Sánchez-Moreno, Marta Larrayoz, Pedro Justicia, Beatriz Perucha, Maialen Martinez-Tabar, Rebeca Martinez-Turrillas, Noelia Casares, Celia Martín-Otal, Marta Gorraiz, Erin W. Meermeier, Marta Chesi, Douglas Lake, P. Leif Bergsagel, Eva Santamaría, María Eréndira Calleja-Cervantes, Patxi San Martín-Uriz, Lorea Jordana-Urriza, Xabier Agirre, Sandra Hervás-Stubbs, Juan Roberto Rodriguez-Madoz, José Ángel Martinez-Climent, Felipe Prosper, Juan José Lasarte; Reprogramming glutamine metabolism enhances BCMA-CAR T-cell fitness and therapeutic efficacy in multiple myeloma. Blood 2025; 146 (24): 2931–2944. doi: https://doi.org/10.1182/blood.2024027496  December 11, 2025 

Overview

Myeloma cells use large amounts of the nutrient glutamine, which can leave too little glutamine for immune cells to work properly. This study explored whether low glutamine levels might limit how well CAR T-cell therapy works in multiple myeloma.

Researchers found that CAR T cells targeting BCMA did not function well when glutamine was scarce. However, when CAR T cells were engineered to take up more glutamine, they multiplied better, produced stronger immune signals, and killed myeloma cells more effectively—even in low-glutamine conditions. In mouse models, these modified CAR T cells controlled myeloma longer and improved survival.

The findings suggest that improving how CAR T cells use glutamine could make CAR T therapy more effective for multiple myeloma and possibly other cancers.

"Glu(tamine)ing together myeloma metabolism and CAR T efficacy"

Source

Arun P. Wiita; Glu(tamine)ing together myeloma metabolism and CAR T efficacy. Blood 2025; 146 (24): 2854–2855. doi: https://doi.org/10.1182/blood.2025031096  December 11, 2025. 

Overview

This commentary discusses new research showing that glutamine, an important nutrient, plays a key role in how well CAR T-cell therapy works in multiple myeloma. Myeloma cells use large amounts of glutamine to survive and grow. Activated T cells, including CAR T cells, also need glutamine to function properly. When myeloma cells use up most of the available glutamine in the bone marrow, CAR T cells may not work as effectively.

The researchers showed in advanced mouse models that CAR T cells engineered to take up more glutamine were stronger, lasted longer, and controlled myeloma better. This work helps explain why some patients relapse after CAR T therapy and opens the door to new strategies to improve CAR T-cell treatments in multiple myeloma.

"Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study"

Source

Ajai Chari, Niels W. C. J. van de Donk, Bhagirathbhai Dholaria, Katja Weisel, María-Victoria Mateos, Hartmut Goldschmidt, Thomas G. Martin, Daniel Morillo, Donna Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D’Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Deeksha Vishwamitra, Sheri Skerget, Raluca I. Verona, Kalpana Bakshi, Lijuan Kang, Thomas J. Prior, Lien Vandenberk, Jaszianne Tolbert, Sangmin Lee, M. Damiette Smit, Ralph Wäsch; Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood 2025; 146 (24): 2902–2913. doi: https://doi.org/10.1182/blood.2025029360  December 11, 2025. 

Overview

This early-phase study tested a combination of two immune-based treatments—talquetamab and daratumumab—in people with heavily pretreated relapsed or refractory multiple myeloma. Talquetamab helps T cells recognize myeloma cells, while daratumumab targets CD38 and can improve the immune environment.

Most patients in the study responded to the combination, with about 7 to 8 out of 10 seeing their disease shrink. Responses also lasted a long time, with many patients remaining progression-free for nearly two years. Side effects were common and included mouth sores, skin reactions, cytokine release syndrome, and infections, but they were generally expected and manageable.

Overall, the results suggest that combining talquetamab with daratumumab may provide deeper and longer-lasting responses for patients with advanced multiple myeloma.

"Improving MM outcomes with bispecific antibody combinations"

Source

Faith E. Davies, Gareth J. Morgan; Improving MM outcomes with bispecific antibody combinations. Blood 2025; 146 (24): 2850–2851. doi: https://doi.org/10.1182/blood.2025031256  December 11, 2025. . 

Overview

This commentary reviews a study that tested whether combining two myeloma drugs—talquetamab and daratumumab—works better than using either drug alone in people with relapsed or refractory multiple myeloma. The key question was whether the combination could improve responses without causing unacceptable side effects.

The authors highlight that this combination has a strong scientific rationale. Daratumumab may improve the immune environment, allowing talquetamab to work more effectively. In the TRIMM-2 study, most heavily pretreated patients responded to the combination, and responses lasted longer than typically seen with single-agent treatment. Side effects were common but similar to what is already known for each drug.

Overall, this commentary supports combining talquetamab with daratumumab as a promising approach to achieve deeper and longer-lasting responses in advanced multiple myeloma, while maintaining manageable safety.

"Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response"

Source

Besse A, Kraus M, Totu T, Buljan M, Janssen AP, van der Stelt M, Matisikova K, Veprkova J, Sedlarikova L, Jurinakova T, Truger M, Haferlach C, Lopez MM, Kortum MK, Rasche L, Driessen C, Besse L. Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response. Haematologica; https://doi.org/10.3324/haematol.2025.289245 [Early view].   December 11, 2025. 

Overview

This study explored a new way to overcome resistance to proteasome inhibitors, a common challenge in treating multiple myeloma. Researchers found that myeloma cells rely on insulin and IGF-1 signaling to survive and manage the high protein load they produce.

The study showed that ceritinib, a drug already approved for another cancer, can block this signaling and, when combined with the proteasome inhibitor carfilzomib, effectively kills resistant myeloma cells. This combination caused protein buildup and stress in the cancer cells, leading to cell death.

These results suggest that ceritinib plus carfilzomib could be a promising strategy to treat patients whose myeloma no longer responds to standard proteasome inhibitors and should be tested in clinical trials.

"Genomically Smoldering Multiple Myeloma Is Not a Distinct Entity But a Collection of Monoclonal Gammopathy of Undetermined Significance or Multiple Myeloma"

Source

Aktas Samur A, Corre J, Talluri S, Shah P, Graffeuil A, Rivera J, Fan Y, Dakiki Korucu B, Szalat R, Fulciniti M, Anderson KC, Sperling A, Parmigiani G, Avet-Loiseau H, Munshi NC, Samur MK. Genomically Smoldering Multiple Myeloma Is Not a Distinct Entity But a Collection of Monoclonal Gammopathy of Undetermined Significance or Multiple Myeloma. J Clin Oncol. 2025 Dec 11:JCO2500289. doi: 10.1200/JCO-25-00289. 

Overview

This study looked at whether genetic changes in myeloma cells can help predict which people with smoldering multiple myeloma (SMM) are more likely to progress to active disease. Researchers compared genetic data from patients with SMM who later developed multiple myeloma and from patients whose SMM did not progress.

They found that in patients who progressed, myeloma-related genetic changes were already present during the smoldering stage. In contrast, patients who did not progress had fewer genetic changes and lacked certain high-risk features. Using this information, the researchers developed a genetic scoring system that identified low-risk SMM patients who were unlikely to progress.

These findings suggest that genetics could improve how SMM risk is assessed and help guide earlier and more personalized treatment decisions in the future.

"Application of individualized low-protein diet nursing for managing multiple myeloma patients with renal impairment"

Source

Ling, Xiao MMa; Yu, Meimei MMa,*. Application of individualized low-protein diet nursing for managing multiple myeloma patients with renal impairment. Medicine 104(50):p e46087, December 12, 2025. | DOI: 10.1097/MD.0000000000046087  December 12, 2025. 

Overview

This study looked at whether a personalized low-protein diet (ILPD) could help people with multiple myeloma who also have kidney problems. Researchers compared patients who received ILPD nursing with those who followed a routine diet.

After one year, patients on the individualized diet had better kidney function, higher protein levels in their blood, stable weight, less inflammation, and improved quality of life. They also experienced fewer side effects compared with the control group.

Overall, this study suggests that ILPD nursing is a safe and effective way to support kidney health, nutrition, and well-being in multiple myeloma patients with renal impairment.

"Genome-wide copy number profiling enhances risk stratification in multiple myeloma by shallow whole-genome sequencing"

Source

Baijun Fang, Zunmin Zhu, Yinyin Chang, Xiangxiang He, Shiyong Li, Manqian Li, Susu Yan, Dandan Zhu, Zhenling Li, Mao Mao; Genome-wide copy number profiling enhances risk stratification in multiple myeloma by shallow whole-genome sequencing. Blood Adv 2025; bloodadvances.2025018133. doi: https://doi.org/10.1182/bloodadvances.2025018133  December 12, 2025.  

Overview

This study evaluated a new test called LeukoPrint, which uses shallow whole-genome sequencing to detect genetic changes called copy number aberrations (CNAs) in multiple myeloma. These changes help doctors predict disease risk and guide treatment decisions.

LeukoPrint detected abnormalities in far more patients than standard karyotyping and closely matched FISH testing for key high-risk markers. When combined with FISH, it improved risk classification, identifying some patients previously considered standard-risk who may benefit from more intensive therapy.

Overall, LeukoPrint provides a more comprehensive and accurate way to assess genetic risk in multiple myeloma, helping doctors tailor treatment strategies.

"Immune Effector Cell-Associated HLH-Like Syndrome (IEC-HS) in CAR-T and TCE-Treated Myeloma and B-Cell Malignancies: Insights from a Pharmacovigilance Study, Transplantation and Cellular Therapy"

Source

Sohaib Irfan, Fathima Shehnaz Ayoobkhan, Nikhil Vojjala, Raabia Qureshi, Raeef Rahman, Ishita Kamboj, Al-Ola Abdallah, Joseph McGuirk, Zahra Mahmoudjafari, Forat Lutfi, Nausheen Ahmed, Immune Effector Cell-Associated HLH-Like Syndrome (IEC-HS) in CAR-T and TCE-Treated Myeloma and B-Cell Malignancies: Insights from a Pharmacovigilance Study, Transplantation and Cellular Therapy, 2025, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2025.12.947. December 12, 2025. 

Overview

This study looked at a rare but serious side effect called immune effector cell-associated hemophagocytic syndrome (IEC-HS) in patients receiving CAR-T or T-cell engager (TCE) therapies for multiple myeloma and certain lymphomas. IEC-HS can cause low blood counts, liver problems, clotting issues, and inflammation, and it can be life-threatening.

Using FDA safety data, the researchers found that IEC-HS was reported in about 1.6% of patients, with a high mortality rate of 61%. Certain CAR-T products, including tisa-cel and cilta-cel, showed higher-than-expected reports of IEC-HS, while others, like axi-cel, reflected high usage rather than increased risk. Teclistamab showed a lower likelihood of causing IEC-HS.

Overall, while IEC-HS is rare, it is serious, and careful monitoring and statistical analysis are needed to understand the risks with different CAR-T and TCE therapies.

"Biological Differences, Yet Comparable Outcomes: A Retrospective Study on the Impact of Treatment Strategy on Light Chain vs. Intact Immunoglobulin Myeloma"

Source

Reshmy, G.S., Gayathri, S., Soman, A. et al. Biological Differences, Yet Comparable Outcomes: A Retrospective Study on the Impact of Treatment Strategy on Light Chain vs. Intact Immunoglobulin Myeloma. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-025-02260-z  December 12, 2025. 

Overview

This study compared two types of multiple myeloma—intact immunoglobulin myeloma (IIM) and light chain myeloma (LCM)—in Indian patients to understand differences in patient characteristics, treatment, and outcomes. Researchers analyzed 316 newly diagnosed patients and found that LCM patients tended to have more severe kidney problems, higher disease markers, and more advanced disease at diagnosis compared with IIM patients.

Treatment choice affected responses: LCM patients responded better to the VRD regimen than VCD and often received simpler maintenance therapy. Despite these differences, overall survival and progression-free survival were similar between the two groups.

The study highlights that tailoring therapy to disease severity at diagnosis is key to achieving the best outcomes in multiple myeloma.

"European Expert Recommendations on Teclistamab Management for Relapsed or Refractory Multiple Myeloma"

Source

Paula Rodríguez-Otero, Philippe Moreau, Maria Victoria Mateos, Maria Theresa Krauth, Leo Rasche, Efstathios Kastritis, Albert Oriol, Elena Zamagni, Claire Albrecht, Eva Rubio Azpeitia, Niels W.C.J. van de Donk, European Expert Recommendations on Teclistamab Management for Relapsed or Refractory Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025,ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.003.  December 13, 2025

Overview

This review focuses on teclistamab, a new bispecific antibody used to treat patients with relapsed or refractory multiple myeloma (RRMM) who have already been exposed to the three main drug classes. Teclistamab targets BCMA, helping the immune system attack myeloma cells, and has shown strong, lasting responses with an acceptable safety profile.

The article provides guidance for doctors on using teclistamab in everyday practice. It covers selecting the right patients—including elderly, frail, or those with kidney problems—starting therapy, and preventing or managing side effects. The goal is to help physicians use teclistamab safely and effectively to improve outcomes in patients with heavily treated multiple myeloma.

"Predictive values of baseline 18F-FDG PET/CT for toxicities and outcomes in patients with relapsed or refractory multiple myeloma following BCMA CAR T-cell therapy"

Source

Xiao, P., Zhao, X., Wang, L. et al. Predictive values of baseline 18F-FDG PET/CT for toxicities and outcomes in patients with relapsed or refractory multiple myeloma following BCMA CAR T-cell therapy. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02769-x  December 13, 2025. 

Overview

This study looked at whether PET/CT scans can help predict serious side effects and outcomes in patients with relapsed or refractory multiple myeloma (R/R MM) receiving BCMA CAR T-cell therapy. Researchers studied 62 patients and measured two key PET/CT markers: metabolic tumor volume (MTV) and total lesion glycolysis (TLG).

Patients with high MTV or high TLG were more likely to develop severe cytokine release syndrome (CRS), a potentially dangerous immune reaction, and often needed treatment with tocilizumab. High MTV and TLG were also linked to poorer long-term survival.

These findings suggest that PET/CT measurements before therapy can help identify patients at higher risk for severe side effects and worse outcomes, helping doctors better plan treatment and monitoring.

"Rising Prevalence of Central Nervous System Involvement in Multiple Myeloma: A 2012-2020 National Inpatient Sample (NIS) Analysis in the United States"

Source

Charles J. Mazof, Vishva Natarajan, Augustos Vrattos, Parth Shah, Frederick Lansigan, Jennifer Hong, Rising Prevalence of Central Nervous System Involvement in Multiple Myeloma: A 2012-2020 National Inpatient Sample (NIS) Analysis in the United States, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.004. December 15, 2025. 

Overview

This study examined trends in central nervous system involvement in multiple myeloma (CNS-MM), a rare and aggressive complication affecting about 1% of patients. Researchers analyzed U.S. hospital data from 2012 to 2020 to see how common CNS-MM has become and whether outcomes have changed.

The study found that CNS-MM prevalence rose sharply by 166% over this period, much faster than the overall increase in multiple myeloma cases. Despite more patients receiving CNS-targeted diagnostic or treatment procedures, survival rates in the hospital did not improve.

These findings show that CNS-MM is becoming more common, but outcomes remain poor, highlighting the need for better understanding and new treatment strategies.

"Gain/Amplification 17p as a Potential Favorable Prognostic Factor in Multiple Myeloma: A Real-World Settings Retrospective Study"

Source

T. Wang, S. Cui, J. Wang, et al. “Gain/Amplification 17p as a Potential Favorable Prognostic Factor in Multiple Myeloma: A Real-World Settings Retrospective Study.” eJHaem 6, no. 6 (2025): e70195. https://doi.org/10.1002/jha2.70195  December 15, 2025. 

Overview

This study looked at a specific genetic change in multiple myeloma called 17p gain/amplification (17p+), and how it affects patient outcomes. Researchers analyzed 125 patients’ genetic profiles and compared results with other high-risk changes, such as deletion of 17p (del(17p)) and 1q21 gain/amplification (1q21+).

The results showed that patients with 17p+ had longer periods before disease progression, longer times before needing their next treatment, and better overall survival compared with patients who had del(17p). Even in patients with other high-risk features like 1q21+, having 17p+ improved some outcomes.

These findings suggest that 17p+ is a favorable genetic marker in multiple myeloma and may help guide personalized treatment decisions.

"Survival outcomes after front-line consolidation with high-dose Melphalan and autologous stem cell transplantation in younger and elderly multiple myeloma patients: a retrospective bi-centric analysis"

Source

Arne Strotmann, Theo Leitner, Paolo Mazzeo, Georg Evers, Alexander Pohlmann, Christine Eisfeld, Maximilian Seib, Nikolas von Bubnoff, Georg Lenz, Evgenii Shumilov, Cyrus Khandanpour, Survival outcomes after front-line consolidation with high-dose Melphalan and autologous stem cell transplantation in younger and elderly multiple myeloma patients: a retrospective bi-centric analysis, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650  https://doi.org/10.1016/j.clml.2025.12.008. December 15, 2025.

Overview

This study examined whether high-dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) benefits younger and older multiple myeloma (MM) patients. Researchers analyzed outcomes in 517 patients, comparing those under 70 years old with those 70 or older who received HDCT/ASCT versus those who did not.

The results showed that HDCT/ASCT improved both the length of time before disease progression and overall survival in all patients. Elderly patients who received HDCT/ASCT had longer disease-free periods than younger patients, while younger patients had longer overall survival.

These findings suggest that age alone should not prevent patients from receiving HDCT/ASCT, and eligibility should be based on overall health and fitness rather than age.

"Characteristics and utilization of the three BCMA-targeted therapies in multiple myeloma"

Source

Mihara, K., Miyama, T. Characteristics and utilization of the three BCMA-targeted therapies in multiple myeloma. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04128-4 December 15, 2025. 

Overview

This review explains three treatments that target BCMA, a protein mainly found on multiple myeloma cells: CAR-T cell therapy, bispecific antibodies (BsAbs), and antibody–drug conjugates (ADCs). Targeting BCMA allows these therapies to attack myeloma cells while mostly sparing normal cells.

CAR-T therapies, like ide-cel and cilta-cel, can produce strong responses, with cilta-cel showing signs of long-term remission. BsAbs such as teclistamab and elranatamab are ready-to-use treatments but may cause T-cell exhaustion. ADCs, like belantamab mafodotin, can cause eye-related side effects.

The order in which these treatments are given matters, because earlier therapies can affect later effectiveness. Checking BCMA levels and T-cell function helps doctors choose the best treatment plan to improve outcomes for patients with multiple myeloma.

"Prognostic Value of [18F]FDG PET/CT in Multiple Myeloma Patients at the Time of Initial Diagnosis"

Source

Mirshahvalad, Seyed Ali MD*; Alghamdi, Ahmed MD*; Chavoshi, Mohammadreza MD*; Felder, Cornel MD*; Metser, Ur MD*; Kukreti, Vishal MD†; Lancman, Guido MD†; Stewart, A. Keith MD†; Veit-Haibach, Patrick MD*. Prognostic Value of [18F]FDG PET/CT in Multiple Myeloma Patients at the Time of Initial Diagnosis. Clinical Nuclear Medicine ():10.1097/RLU.0000000000006270, December 16, 2025. | DOI: 10.1097/RLU.0000000000006270 

Overview

This study looked at whether PET/CT scans and routine lab tests could help predict outcomes in patients newly diagnosed with multiple myeloma (MM). Researchers analyzed 42 patients using [18F]FDG-PET/CT scans to measure tumor activity in the bone marrow, focal lesions, and the whole body, along with clinical factors like lab values.

They found that a high bone marrow SUVmax on PET/CT and the presence of disease outside the bone marrow (extramedullary disease) were linked to worse survival. Among lab tests, a high serum β2-microglobulin level also predicted poorer outcomes. Combining imaging and clinical markers may help doctors better estimate prognosis and guide treatment decisions in newly diagnosed MM patients.

"Daratumumab bortezomib and dexamethasone in transplant ineligible newly diagnosed elderly myeloma patients (AMN006)—a trial by Asian Myeloma Network (NCT03695744)"

Source

Tan, M. S. Y., Nagarajan, C., Ooi, M., De Mel, S., Binte Hashim, N. S., Li, X., … Chng, W. J. (2025). Daratumumab bortezomib and dexamethasone in transplant ineligible newly diagnosed elderly myeloma patients (AMN006)—a trial by Asian Myeloma Network (NCT03695744). Leukemia & Lymphoma, 1–8. https://doi.org/10.1080/10428194.2025.2602050  December 16, 2025. 

Overview

This study evaluated a treatment combination of daratumumab, bortezomib, and dexamethasone (DVd) in elderly patients with newly diagnosed multiple myeloma (NDMM) who were not eligible for stem cell transplant. A total of 27 patients received nine months of DVd followed by ongoing daratumumab maintenance.

Results were encouraging: 96% of patients responded to treatment, with nearly 30% achieving complete remission and most of these being minimal residual disease (MRD) negative. After a median follow-up of 27 months, the median progression-free survival was 36.5 months, and overall survival was not reached. The regimen was generally well tolerated, with 22% experiencing drug-related side effects. This study supports DVd followed by daratumumab maintenance as an effective and manageable frontline option for transplant-ineligible NDMM patients.

"Multiple myeloma in Mexico: a retrospective study on long-term survival in a publicly insured cohort"

Source

Solis-Poblano, J. C., Itzmoyotl-Hernández, M. T., Pérez-Lozano, U., García-Stivalet, L. A., López-Marthen, J. L., Silva-Ruacho, R., … Vela-Ojeda, J. (2025). Multiple myeloma in Mexico: a retrospective study on long-term survival in a publicly insured cohort. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2602042  December 16, 2025. 

Overview

This study looked at outcomes in 293 adults with multiple myeloma treated at a public hospital between 2002 and 2024. The goal was to identify factors that influence survival, especially in settings where advanced genetic testing may not be available.

After nearly 3 years of follow-up, overall survival at 3, 5, and 10 years was 84%, 76%, and 60%, respectively. Patients who underwent autologous stem-cell transplant (ASCT) had better long-term survival, though this benefit was not significant after adjusting for other factors. Higher hemoglobin levels were linked to better survival, while higher lactate dehydrogenase (LDH) levels were linked to worse outcomes. Median progression-free survival was 3.9 years. These findings suggest that simple blood tests like hemoglobin and LDH can help guide prognosis and timely ASCT referral, particularly in resource-limited settings without access to cytogenetic testing.

"Skeletal health in the precursor stages of multiple myeloma: fracture risk and bone phenotypes in monoclonal gammopathy of undetermined significance and smouldering myeloma"

Source

Melissa D. Cantley, Laura J. Trainor, Emma A-J. Cheney, Suzanne M. Watt, Kate Vandyke, Skeletal health in the precursor stages of multiple myeloma: fracture risk and bone phenotypes in monoclonal gammopathy of undetermined significance and smouldering myeloma, Pathology, 2025, ISSN 0031-3025, https://doi.org/10.1016/j.pathol.2025.11.002. December 16, 2025.  

Overview

This study focuses on bone health in people with multiple myeloma (MM) and its precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Up to 80% of MM patients develop bone disease, which increases fracture risk and causes pain that affects quality of life. While MGUS and SMM are usually symptom-free and patients are not treated, research shows that some may already have changes in bone structure. Patients with MGUS or progressing SMM may have increased bone breakdown, especially near plasma cells, which can raise fracture risk. Currently, there are no standard guidelines for monitoring bone health in these early stages. Understanding these early skeletal changes may help identify patients at higher risk and guide future prevention strategies.

"Expression and Clinical Significance of BCL2 Interacting Protein 3 Like (BNIP3L) in Serum of Patients with MM"

Source

Nong, Y., Xiong, Z., Wang, Q., Gu, M., Zheng, Y., Wang, Y., … Li, R. (2025). Expression and Clinical Significance of BCL2 Interacting Protein 3 Like (BNIP3L) in Serum of Patients with MM. Blood and Lymphatic Cancer: Targets and Therapy, 15, 247–264. https://doi.org/10.2147/BLCTT.S557238  December 17, 2025.  

Overview

This study examined whether the protein BNIP3L in the blood can help diagnose and predict outcomes in multiple myeloma (MM). Researchers measured serum BNIP3L in 152 MM patients and 158 healthy individuals and found that levels were significantly higher in patients with MM. Higher BNIP3L was linked to more aggressive disease features, including spread outside the bone marrow and high-risk genetic changes. Patients with better treatment responses or who received stem cell transplants had lower BNIP3L levels. Overall, elevated BNIP3L may indicate worse outcomes, suggesting that measuring it could help track disease progression and guide prognosis in MM patients.

"Plasma cell development-based prediction of prognosis and treatment response in individual multiple myeloma"

Source

Jiang, S., Yang, Y., Yao, M. et al. Plasma cell development-based prediction of prognosis and treatment response in individual multiple myeloma. Front. Med. (2025). https://doi.org/10.1007/s11684-025-1184-9  December 17, 2025.  

Overview

This study developed a new tool, called the myeloma classification score (MCS), to better predict outcomes and treatment responses in multiple myeloma (MM). By analyzing gene expression patterns in MM cells, researchers identified patterns linked to disease progression and drug response. In more than 2,000 patients with newly diagnosed or relapsed/refractory MM, MCS distinguished between stable and progressive disease and predicted responses to therapies like bortezomib and carfilzomib. MCS also highlighted distinct molecular pathways that could be targeted in treatment. Overall, this score offers a personalized way to assess risk and guide therapy decisions for individual MM patients.

"Elranatamab Exposure–Safety Analysis in Relapsed or Refractory Multiple Myeloma"

Source

Soltantabar, P., Hibma, J., Wang, D., Conte, U., Hickman, A. and Elmeliegy, M. (2026), Elranatamab Exposure–Safety Analysis in Relapsed or Refractory Multiple Myeloma. J Clin Pharm, 66: e70130. https://doi.org/10.1002/jcph.70130  December 17, 2025. 

Overview

This study examined the safety of elranatamab, a bispecific antibody used to treat relapsed or refractory multiple myeloma (RRMM). Researchers analyzed data from four clinical trials to see if higher drug exposure increased the risk of serious side effects such as infections, low blood counts, or treatment interruptions. The analysis found no significant link between elranatamab exposure and these safety events, meaning patients on the standard 76 mg once-weekly dose had a similar risk of side effects as those on lower doses. These results support using the full dose and managing side effects with temporary treatment pauses rather than reducing the dose.

"ID2 Suppresses Multiple Myeloma Cell Proliferation by Repressing the Activity of the Transcription Factor TCF3"

Source

Mariateresa Fulciniti, Yao Yao, Tommaso Perini, Jessica Fong Ng, Anaïs Schavgoulidze, Shuhui Deng, Jian Cui, Jessica Encinas Mayoral, Francesco Ladisa, Ryan M. Young, Charles B. Epstein, Cassandra M. White, Christopher J. Ott, Annamaria Gulla, Shannon M. Matulis, Adam S. Sperling, Eugenio Morelli, Lawrence H. Boise, Moritz Binder, Raphael Szalat, Mehmet K. Samur, Kenneth C. Anderson, Nikhil C. Munshi; ID2 Suppresses Multiple Myeloma Cell Proliferation by Repressing the Activity of the Transcription Factor TCF3. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0048  December 17, 2025. 

Overview

This study explored how multiple myeloma (MM) cells rely on certain transcription factors for growth. Researchers discovered that the gene ID2 acts as a tumor suppressor by controlling the activity of the transcription factor TCF3. In MM cells, ID2 levels are often low, allowing TCF3 to drive cell proliferation. Increasing ID2 levels blocked TCF3 activity, stopping MM cell growth. The bone marrow environment further reduces ID2 and boosts TCF3 activity, helping cancer cells grow. These findings reveal how MM cells exploit this pathway to proliferate, highlighting potential targets for therapies that could disrupt this tumor-promoting mechanism.

"Talquetamab in Japanese patients with relapsed/refractory multiple myeloma in the MonumenTAL-1 study"

Source

Ito, S., Kuroda, Y., Sunami, K. et al. Talquetamab in Japanese patients with relapsed/refractory multiple myeloma in the MonumenTAL-1 study. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04134-6  December 17, 2025.  

Overview

This study evaluated talquetamab, a bispecific antibody, in Japanese patients with relapsed or refractory multiple myeloma (RRMM). Thirty-six patients received weekly talquetamab and were followed for a median of 13.4 months. The treatment showed strong effectiveness, with 78% of patients responding and 56% achieving a complete response or better. Responses occurred quickly, with a median time of 1.2 months. One-year rates of ongoing response, progression-free survival, and overall survival were 66%, 56%, and 74%, respectively. Side effects, including taste changes, skin and nail issues, rash, and cytokine release syndrome, were common but mostly mild. Infections occurred in about half of patients, with serious infections in 17%. Overall, talquetamab demonstrated meaningful benefits for Japanese patients with RRMM, consistent with global study findings.

"Selective depletion of B-cell subsets underlies increased risk of infection in MM patients treated with anti-BCMA vs -GPRC5D bsAbs"

Source

Tomas Jelinek, David Žihala, Aintzane Zabaleta, Ioannis V Kostopoulos, Ondrej Soucek, Ondrej Venglar, Cristina Moreno, Despina Fotiou, Eva Radova, Luis-Esteban Tamariz-Amador, Foteini Theodorakakou, Ludmila Muronova, Andrea Manubens, Ourania Tsitsilonis, Tereza Popková, Carmen Gonzalez, Anjana Anilkumar Sithara, Francesco Corrado, Nayda Bidikian, Camila Guerrero, Veronika Kapustova, Daniel Bilek, Patrick Ryan Hagner, Marta Larrayoz, Jose A Martínez-Climent, Lucie Broskevičová, Jana Mihalyova, Maximillian Merz, Tereza Sevcikova, Irene M. Ghobrial, Jesús F. San-Miguel, Meletios A Dimopoulos, Paula Rodriguez-Otero, Jakub Radocha, Efstathios Kastritis, Bruno Paiva, Roman Hajek; Selective depletion of B-cell subsets underlies increased risk of infection in MM patients treated with anti-BCMA vs -GPRC5D bsAbs. Blood 2025; blood.2025029572. doi: https://doi.org/10.1182/blood.2025029572  December 17, 2025.  

Overview

This study examined why certain bispecific antibodies (bsAbs) used to treat multiple myeloma (MM) cause different rates of infections. Researchers found that anti-BCMA bsAbs not only target malignant plasma cells (PCs) but also deplete normal B cells, including early-stage pre-B cells, in the bone marrow. In contrast, anti-GPRC5D bsAbs mainly target plasma cells and spare normal B cells. This broad depletion by anti-BCMA bsAbs likely explains the higher infection risk seen in patients. These findings provide a clearer understanding of how these therapies affect the immune system and suggest ways to tailor bsAb treatments to reduce infection risk while maintaining anti-myeloma activity.

"RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma"

Source

Valuskova, Z., Cholujova, D., Beke, G., Hucko, M., Marinkovicova, M. E., Suroviakova, K., … Jakubikova, J. (2025). RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma. Cancer Biology & Therapy, 26(1). https://doi.org/10.1080/15384047.2025.2603100  December 18, 2025 

Overview

This study investigated how two common multiple myeloma (MM) treatment regimens—RVd (lenalidomide, bortezomib, dexamethasone) and CyBorD (cyclophosphamide, bortezomib, dexamethasone)—affect plasma cells and B-cell development in the bone marrow. Researchers found that both therapies changed the activity of key genes and proteins involved in B-cell and plasma cell maturation, but in different ways. RVd and CyBorD also had overlapping effects, such as altering markers related to cell survival and immune function. These findings help explain why the regimens work, show how responders differ from non-responders, and could guide personalized therapy choices for MM patients.

"Toward functional cure in relapsed/refractory multiple myeloma: long-term outcomes from CARTITUDE-1 study cement the role of CAR-T cell"

Source

de Soto, T., Moukalled, N. & Mohty, M. Toward functional cure in relapsed/refractory multiple myeloma: long-term outcomes from CARTITUDE-1 study cement the role of CAR-T cells. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02782-0  December 18, 2025. 5 

Overview

This study reports long-term outcomes from the CARTITUDE-1 trial, which evaluated ciltacabtagene autoleucel (cilta-cel), a BCMA-targeted CAR-T therapy, in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). After a single infusion, 33% of patients remained progression-free at over five years, with deep responses including sustained MRD and PET negativity. Patients with durable responses had lower tumor burden, better blood counts, and healthier T-cell profiles at baseline, highlighting the role of immune fitness in long-term benefit. The therapy was well tolerated, with no new safety concerns beyond five years. These results suggest that cilta-cel can provide long-term, treatment-free remission and may offer a functional cure for some RRMM patients.

"An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden"

Source

Erin W. Meermeier, Kirsten Pfeffer, Caleb K. Stein, Meaghen E. Sharik, Megan T. Du, Yuliza Tafoya Alvarado, Chang-Xin Shi, Yuan Xiao Zhu, P. Leif Bergsagel, Marta Chesi; An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden. Blood 2025; 146 (25): 3072–3085. doi: https://doi.org/10.1182/blood.2025029215  December 18, 2025. 

Overview

This study explored strategies to improve responses to BCMA-targeted bispecific T-cell engagers (TCEs) in multiple myeloma (MM) patients with high tumor burden, who often respond poorly to TCEs alone. Using a mouse model, researchers found that pretreatment with Ikaros-degrading drugs (like IMiDs or CELMoDs) and dexamethasone reshaped T cells in the bone marrow, increased naïve T-cell infiltration, and reduced T-cell exhaustion. This combination allowed TCE therapy to achieve 100% response rates, deeper and more durable remissions, and reduced the risk of severe cytokine release syndrome. These findings suggest a promising strategy to enhance TCE effectiveness while maintaining safety in high-risk MM patients.

"Cytogenetic Testing in Newly Diagnosed Multiple Myeloma: Real World Evidence on Clinical Features and Adverse Outcomes for High Risk Groups"

Source

Ghassan Zammar, Bradley Augustson, Elizabeth Moore, Cameron Wellard, Elham Ashrafi, Hasib Sidiqi, Kenneth J C Lim, Dejan Radeski, Alannah Jackson, Krystal Bergin, Simon Harrison, P Joy Ho, Tracy King, Hang Quach, Peter Mollee, Rajeev Rajagopal, Brian Rosengarten, Erica Wood, Zoe McQuilten, Andrew Spencer, Cytogenetic Testing in Newly Diagnosed Multiple Myeloma: Real World Evidence on Clinical Features and Adverse Outcomes for High Risk Groups., Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.005. December 18, 2025. 

Overview

This study analyzed over 5,900 newly diagnosed multiple myeloma (MM) patients to understand how multiple high-risk genetic changes affect outcomes. Patients with more high-risk cytogenetic abnormalities (HRCA) tended to have worse disease features, such as anemia, higher bone marrow plasma cells, and higher tumor markers. While initial treatment responses were similar, patients with more HRCA had shorter remissions and overall survival. Among the HRCA, del(17p) had the worst impact, and adding additional HRCA did not further worsen outcomes in these patients. These findings highlight the importance of assessing the total number of high-risk genetic changes to guide personalized treatment strategies.

"NEAT1: a multifaceted long non-coding RNA in multiple myeloma"

Source

Benini G, Taranto S, Sciumè M, Rigali F, Marcheselli R, Abate A, Mitola S, Sigala S, Sacco A, Roccaro AM. NEAT1: a multifaceted long non-coding RNA in multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2025.289258 [Early view].  December 18, 2025. 

Overview

This review focuses on NEAT1, a long non-coding RNA, and its role in multiple myeloma (MM), a cancer of plasma cells in the bone marrow. NEAT1 has gained attention in recent years for its potential impact on MM biology. The review highlights how NEAT1 could serve as a biomarker to help detect or monitor the disease and explores its potential as a target for new therapies. Understanding NEAT1 may help guide the development of more precise treatments and improve outcomes for patients living with MM.

"Immune Checkpoint Remodeling Across Disease Progression in Multiple Myeloma"

Source

Valuskova Z, Cholujova D, Beke G, Hucko M, Klucar L, Grofova G, Drgona L, Jakubíková J. Immune Checkpoint Remodeling Across Disease Progression in Multiple Myeloma. Neoplasma. 2025 Dec 18:251026N448. doi: 10.4149/neo_2025_251026N448.

Overview

This study examined how immune cells in the bone marrow change as multiple myeloma (MM) develops and progresses. Researchers analyzed both inhibitory and activating immune checkpoints on B cells, T cells, natural killer (NK) cells, and other immune cells in healthy people, patients with early-stage disease (MGUS), newly diagnosed MM, and relapsed/refractory MM. They found that MM progression causes widespread changes in immune cell types and checkpoint patterns, including loss of certain B and T cell populations and shifts in checkpoint proteins that regulate immune responses. Some checkpoint changes were linked to better progression-free survival. Understanding these patterns may help guide immunotherapy strategies in MM.

"Addition of anti-CD38 monoclonal antibody in newly diagnosed multiple myeloma: Advancing toward quadruplet induction regimens?"

Source

Yuqi Wang, Li Zhang, Dong He, Huan Chen, Hanzhen Zhang, Youhai Yuan, Cuilian Zhang, Ru Feng, Yongqiang Wei, Xiaolei Wei, Addition of anti-CD38 monoclonal antibody in newly diagnosed multiple myeloma: Advancing toward quadruplet induction regimens? A Systematic Review and Meta-Analysis, Blood Neoplasia, 2025, 100189, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100189.  December 18, 2025. 

Overview

This study reviewed 11 clinical trials with over 5,500 patients to examine the benefits of adding anti-CD38 antibodies (daratumumab or isatuximab) to standard treatments for newly diagnosed multiple myeloma (NDMM). The analysis found that anti-CD38 therapy significantly increased the chances of achieving minimal residual disease (MRD) negativity in both transplant-eligible and transplant-ineligible patients, including those with high-risk disease. It also improved progression-free survival across all patient groups. However, treatment was associated with higher rates of infections, neutropenia, and low platelets. Overall, anti-CD38 therapy is effective but requires careful monitoring for side effects.

"Circulating tumor cells in myeloma are a compound biomarker for bone marrow high-risk genomic alterations and tumor load"

Source

Cathelijne Fokkema, Luca Bertamini, Madelon M.E. de Jong, Sabrin Tahri, Davine Hofste op Bruinink, Zoltan Kellermayer, Natalie Papazian, Chelsea den Hollander, Michael Vermeulen, Elodie C.G. Stoetman, Gregory van Beek, Remco Hoogenboezem, Vincent H.J. van der Velden, Cyrille Hulin, Aurore Perrot, Philippe Moreau, Melissa Rowe, Diego Vieyra, Robin Carson, Mark van Duin, Mathijs Arnoud Sanders, Annemiek Broijl, Peter Sonneveld, Tom Cupedo; Circulating tumor cells in myeloma are a compound biomarker for bone marrow high-risk genomic alterations and tumor load. Blood 2025; blood.2025030083. doi: https://doi.org/10.1182/blood.2025030083  December 18, 2025. 

Overview

This study investigated why high levels of circulating tumor cells (CTCs) predict poor outcomes in newly diagnosed multiple myeloma. By analyzing paired blood and bone marrow samples, researchers found that CTCs are transcriptionally very similar to bone marrow tumor cells and do not represent a separate tumor population. High CTC levels were linked to increased tumor cell proliferation and specific genetic abnormalities, including high-risk mutations and chromosomal changes. Overall, CTC levels reflect both tumor burden and underlying genomic risk, making them a strong biomarker for identifying patients with aggressive disease and guiding treatment decisions

"Real-world outcomes of high-dose melphalan and autologous stem cell transplantation in patients with multiple myeloma older and younger than 65 years"

Source

Koen M. Klomberg, Miriam Gelderloos, Hilde A.M. Kooistra, Marcel Nijland, Geertruida H. de Bock, Gerwin A. Huls, Mirian Brink, Wilfried W.H. Roeloffzen, Wouter J. Plattel, Real-world outcomes of high dose melphalan and autologous stem cell transplantation in patients with multiple myeloma older and younger than 65 years, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.007. December 18, 2025. 

Overview

This study looked at outcomes of high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) in multiple myeloma patients over 65 compared with younger patients. Researchers analyzed 394 patients and found that older patients (>65) had similar overall survival, time to next treatment or disease-related death, complication rates, and long-term quality of life as those 65 or younger. Transplant-related mortality was low at 1%, and serious complications were uncommon. These findings show that HDT/ASCT is safe and effective in fit older patients, supporting its use beyond traditional age limits.

"Relative Effectiveness of Talquetamab Versus Real-World Physician’s Choice Treatment Regimens in Patients With Relapsed/Refractory Multiple Myeloma: Updated Results From an Indirect Treatment Comparison"

Source

Jing Christine Ye, Noa Biran, Sandhya Nair, Xiwu Lin, Keqin Qi, Eric M. Ammann, Thomas Renaud, Bonnie W. Lau, Jenny Zhang, Trilok Parekh, Kathleen S. Gray, Xinke Zhang, Luciano J. Costa, Relative Effectiveness of Talquetamab Versus Real-World Physician’s Choice Treatment Regimens in Patients With Relapsed/Refractory Multiple Myeloma: Updated Results From an Indirect Treatment Comparison, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.009. December 19, 2025.  

Overview

This study compared the effectiveness of talquetamab, a treatment for relapsed/refractory multiple myeloma (RRMM), with standard real-world therapies. Using updated data from the MonumenTAL-1 trial and a real-world database, researchers analyzed outcomes for patients receiving talquetamab either weekly (0.4 mg/kg) or every two weeks (0.8 mg/kg). Talquetamab significantly improved progression-free survival, time to next treatment, and overall survival compared with real-world treatments, including in patients who had received four or more prior therapies. These results support talquetamab as a highly effective treatment option for eligible patients with RRMM.

"BCMA biology and therapeutic targeting in multiple myeloma: from ligand signaling to antigen escape"

Source

Ebru Sezer, Seungyoun Lee, Junho Chung, BCMA biology and therapeutic targeting in multiple myeloma: from ligand signaling to antigen escape, Seminars in Hematology, 2025, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2025.12.004. December 19, 2025 

Overview

This review explains the role of B-cell maturation antigen (BCMA) in multiple myeloma (MM) and its importance as a treatment target. BCMA helps plasma cells survive and supports myeloma growth, with signaling pathways that promote cancer cell proliferation. Therapies targeting BCMA include CAR T-cell therapies, bispecific T-cell engagers, and antibody-drug conjugates, which have shown strong effectiveness in relapsed/refractory MM. The review also highlights challenges such as resistance mechanisms, including shedding of BCMA and genetic changes, and discusses strategies to overcome them, such as γ-secretase inhibition or dual-target therapies. BCMA remains a central focus in advancing MM treatment.

"Screening for multiple myeloma has low yield as part of a secondary osteoporosis screen"

Source

Joanna Y. Gong, Sandra Iuliano, Aye N. Tint, Jas-mine Seah, MaiAnh Nguyen, Cherie Chiang, Screening for multiple myeloma has low yield as part of a secondary osteoporosis screen, Pathology, 2025, ISSN 0031-3025, https://doi.org/10.1016/j.pathol.2025.11.004. December 19, 2025. 

Overview

This study looked at how effective routine screening for multiple myeloma (MM) is in older adults who have had a fragility fracture. Over five years, 1,589 patients were tested using blood and urine tests. Only 5% showed abnormal monoclonal proteins, leading to a very small number of new diagnoses: 4.2% had MGUS and 0.3% had MM. The total cost of screening was high, and all newly diagnosed MM cases were already indicated by other routine tests. The findings suggest that universal MM screening after fractures has a low yield and may not be cost-effective.

"Prognostic value of serological and PET/CT response kinetics in patients with multiple myeloma treated with BCMA CAR-T"

Source

Gustine, J.N., Scaringi, J.A., Bauer, F. et al. Prognostic value of serological and PET/CT response kinetics in patients with multiple myeloma treated with BCMA CAR-T. Leukemia (2025). https://doi.org/10.1038/s41375-025-02819-9  December 19, 2025 

Overview

This study looked at how early responses predict outcomes in multiple myeloma (MM) patients treated with BCMA CAR-T therapy. Researchers reviewed 158 patients treated at Massachusetts General Hospital and assessed blood (serologic) and PET/CT responses at 1 and 3 months. They found that patients who achieved a very good partial response (≥VGPR) at 1 month or complete response (CR) at 3 months had much longer progression-free and overall survival, even in patients with extramedullary disease. Early PET/CT negativity at 1 month did not predict survival, possibly due to high tumor burden or timing of scans. Early serologic response can guide risk-adapted treatment strategies.

"The Histone Modifier KANSL2 Is an Actionable Biomarker in Multiple Myeloma"

Source

Kaiting Jiang, Marieluise Kirchner, Frederik Herzberg, Yan Zhao, Amelie Gasper, Francis Baumgartner, Paul Jung, Jan Braune, Veronika Schulze, Konstandina Isaakidis, Philipp Mertins, Jan Krönke, Matthias Wirth, Ulrich Keller, Stefan Habringer; The Histone Modifier KANSL2 Is an Actionable Biomarker in Multiple Myeloma. Mol Cancer Ther 2025; https://doi.org/10.1158/1535-7163.MCT-25-0379  December 19, 2025. 

Overview

This study identifies KANSL2, a gene involved in regulating histone modifications, as a key player in multiple myeloma (MM). High KANSL2 levels were linked to worse outcomes and protection of cancer cells from DNA-damaging stress. Laboratory studies showed that MM cells with high KANSL2 were especially sensitive to certain epigenetic drugs, including HDAC inhibitors (like panobinostat) and BET inhibitors (like OTX-015), either alone or combined. Testing patient samples confirmed this effect. These findings suggest that KANSL2 could serve as both a marker of chemotherapy resistance and a guide for using epigenetic therapies to selectively target high-risk MM cells.

"Evolving treatments and outcomes in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a real-world study in China"

Source

Xiaozhe, L., Meilan, C., Junru, L. et al. Evolving treatments and outcomes in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a real-world study in China. BMC Cancer 25, 1875 (2025). https://doi.org/10.1186/s12885-025-15185-7  December 19, 2025.  

Overview

This study looked at how treatment and outcomes for newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplantation (ASCT) in China have changed from 2007 to 2023. Over time, more patients were older than 65, had extramedullary disease, or had secondary amyloidosis. Treatments shifted toward bortezomib-based regimens and the addition of daratumumab in recent years. Deeper treatment responses were achieved, with pre- and post-ASCT MRD negativity increasing significantly. Five-year progression-free and overall survival rates also improved, especially with tandem ASCT for high-risk patients. These findings show that newer therapies and better risk stratification have substantially improved outcomes in NDMM.

"Preclinical evaluation of TIGIT as a target to enhance efficacy and mitigate T cell exhaustion in multiple myeloma following BCMA-CAR-T therapy"

Source

Xia, Y., Zhu, J., Guo, R. et al. Preclinical evaluation of TIGIT as a target to enhance efficacy and mitigate T cell exhaustion in multiple myeloma following BCMA-CAR-T therapy. Cell Death Dis 16, 890 (2025). https://doi.org/10.1038/s41419-025-08203-w  December 19, 2025.  

Overview

This study investigated why some patients with relapsed/refractory multiple myeloma (RRMM) relapse after BCMA-targeted CAR-T therapy. Researchers found that higher levels of TIGIT, an immune checkpoint protein, were present on T cells from patients who relapsed early, and these levels were linked to higher tumor burden and worse outcomes. Blocking TIGIT in preclinical models reduced T-cell exhaustion, increased CAR-T cell proliferation, and improved anti-tumor activity. These findings suggest that TIGIT plays a key role in CAR-T resistance and that TIGIT inhibition could be a promising strategy to boost CAR-T effectiveness and prevent relapse in multiple myeloma.

"Safety and Efficacy of G-CSF Alone with Pre-Emptive Plerixafor for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Newly Diagnosed Multiple Myeloma"

Source

Youssef Elemary, Waleed Sabry, Julie Stakiw, Mark Bosch, Hadi Goubran, James Sanayei, Shruthi Kodad, Rebecca MacKay, Jill Lacey, Sabuj Sarker, Mohamed Elemary, Safety and Efficacy of G-CSF Alone with Pre-Emptive Plerixafor for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Newly Diagnosed Multiple Myeloma, Transfusion and Apheresis Science, 2025, 104304, ISSN 1473-0502, https://doi.org/10.1016/j.transci.2025.104304. December 20, 2025. 

Overview

This study looked at a new method for collecting stem cells from multiple myeloma patients before autologous stem cell transplant. Using only G-CSF to stimulate stem cells, with pre-emptive use of Plerixafor guided by daily CD34+ cell counts, researchers achieved successful stem cell collection in all 176 patients. Only 14% needed Plerixafor, and most collections required just two days. Patients proceeded to transplant without delays, with fast recovery of blood counts and all surviving to day 100. This approach reduces chemotherapy exposure, limits Plerixafor use, and ensures timely, safe stem cell collection for transplant.

"Ferritin H Knockout Induces Differential Immunomodulatory Drug Responses in Multiple Myeloma Cell Lines"

Source

A. Sharma, L. Pathangey, S. S. Chirackal, K. G. Shim, R. Fonseca, and S. Swaminathan, “Ferritin H Knockout Induces Differential Immunomodulatory Drug Responses in Multiple Myeloma Cell Lines,” European Journal of Haematology (2025): 1–11, https://doi.org/10.1111/ejh.70084.  December 21, 2025. 

Overview

This study explored why some multiple myeloma (MM) cells become resistant to immunomodulatory drugs (IMiDs), a key treatment for the disease. Researchers focused on FTH1, a protein that stores and regulates iron in cells. They found that higher FTH1 levels were linked to IMiD resistance. Removing FTH1 in certain MM cells reduced drug sensitivity, lowered iron and reactive oxygen species levels, and altered stress and calcium-related pathways. These findings suggest that FTH1 and iron regulation play a key role in IMiD resistance, offering a potential target for overcoming treatment resistance in MM.

"Surgical Outcomes in Spinal Multiple Myeloma: A 7-Year Single-Centre Review"

Source

Bharathidasan, V., Palliyil, N.S., Vellara, J. et al. Surgical Outcomes in Spinal Multiple Myeloma: A 7-Year Single-Centre Review. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-025-02276-5  December 21, 2025. 

Overview

This study looked at outcomes for multiple myeloma (MM) patients who had surgery to stabilize their spine due to disease-related fractures or instability. Thirty patients underwent posterior spinal instrumentation, with most showing improved independence after surgery—rising from 3% preoperatively to 53% postoperatively. Complications occurred in 20% of patients, mainly wound infections, but no hardware failures were reported. Both minimally invasive and open surgeries were used. Overall, the study shows that spinal stabilization in MM is safe and effective, leading to significant functional improvement, and that low albumin levels alone should not prevent surgery.

"Impact of CD34+ cell infusion dose on immune reconstitution and survival in multiple myeloma after autologous stem cell transplantation"

Source

Zhang, T., Cheng, X., Jin, Y., Zhang, R., Shen, X., Chen, L., & Shi, Q. (2025). Impact of CD34+ cell infusion dose on immune reconstitution and survival in multiple myeloma after autologous stem cell transplantation. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2604564  December 22, 2025.  

Overview

This study examined how the number of stem cells infused during autologous stem cell transplantation (ASCT) affects outcomes in multiple myeloma patients. In 176 patients, higher CD34+ cell doses (≥5 × 10⁶/kg) were linked to longer progression-free and overall survival, deeper treatment responses, and sustained minimal residual disease (MRD) negativity. High doses also promoted the formation of oligoclonal bands, a sign of immune recovery. Patients with both high CD34+ doses and oligoclonal bands had the best overall survival. The findings suggest that targeting a CD34+ dose of ≥5 × 10⁶/kg is effective for improving survival without additional benefit beyond ~10.6 × 10⁶/kg.

"The effects of daratumumab on bone disease in patients with newly diagnosed multiple myeloma: a multi-center retrospective study"

Source

Li, X., Wang, H., Li, Y. et al. The effects of daratumumab on bone disease in patients with newly diagnosed multiple myeloma: a multi-center retrospective study. BMC Cancer 25, 1880 (2025). https://doi.org/10.1186/s12885-025-15250-1  December 22, 2025   

Overview

This study looked at whether daratumumab (Dara), a CD38-targeted therapy, helps prevent bone complications in multiple myeloma (MM) patients. Among 164 newly diagnosed patients, the overall rate of skeletal-related events (SREs) was lower in those treated with Dara (9.8%) compared with those who did not receive Dara (21.2%), though this difference was not statistically significant. Subgroup analysis showed that patients without high calcium levels at diagnosis had a significant reduction in SREs with Dara. These results suggest Dara may help protect bones in certain MM patients, but further research is needed to confirm its bone-protective effects.

"Structured whole-body MRI highlights clinically relevant disease pattern changes in relapsed/refractory multiple myeloma"

Source

Grözinger, M., Schlanke, M., Gröne, J. et al. Structured whole-body MRI highlights clinically relevant disease pattern changes in relapsed/refractory multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02834-w  December 22, 2025. 

Overview

This study examined how whole-body MRI can help assess disease in multiple myeloma (MM), focusing on relapsed/refractory MM (RRMM) patients. Researchers used two structured scoring systems, MY-RADS and KIM score, on 46 RRMM patients and compared them with 68 newly diagnosed patients. They found that RRMM patients often had more disease outside the bone marrow, such as in soft tissue, while marrow infiltration was lower. Both scoring systems were linked to patient survival, showing that MRI can provide important prognostic information. The study highlights that bone marrow biopsies alone may miss disease, making imaging essential in RRMM.

"Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma"

Source

Askeland, F.B., Bugge, V.H., Rasmussen, AM. et al. Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma. Blood Cancer J. 15, 214 (2025). https://doi.org/10.1038/s41408-025-01407-5  December 22, 2025. 

Overview

This study looked at how patients with newly diagnosed, transplant-eligible multiple myeloma (NDMM) and kidney problems respond to treatment. In the REMNANT trial, 382 patients received four cycles of bortezomib, lenalidomide, and dexamethasone, including 81 patients with renal impairment (RI), seven of whom were on dialysis. Results showed that 77% of patients with RI improved kidney function, and five dialysis-dependent patients became dialysis-free. Overall treatment responses and side effects were similar between patients with and without RI, though anemia and low platelets were more common in RI patients. The study suggests higher lenalidomide dosing is safe and effective in this group.

"Progressive NK-cell dysfunction and ILC imbalance favor immune evasion in multiple myeloma"

Source

Maria Teresa Bilotta, Antonio Giovanni Solimando, Vanessa Desantis, Lucia Di Marzo, Andrea Sabatini, Sergio Forcelloni, Alessandro Andriano, Arcangelo Morizio, Antonella Argentiero, Roberto Ria, Linda Quatrini, Lorenzo Moretta, Paola Vacca, Nicola Tumino; Progressive NK-cell dysfunction and ILC imbalance favor immune evasion in multiple myeloma. Blood Adv 2025; 9 (24): 6246–6251. doi: https://doi.org/10.1182/bloodadvances.2025016659  December 23, 2025. 

Overview

This study explored how the innate immune system changes as multiple myeloma (MM) progresses. Researchers analyzed natural killer (NK) cells and innate lymphoid cells (ILCs) in blood and bone marrow from patients at different stages, from early precursor conditions to newly diagnosed MM. They found that although NK cells increase in number, their ability to kill cancer cells decreases, partly due to loss of CD16, a key receptor for antibody therapies. ILC1 cells, which normally support anti-cancer immunity, decreased, while ILC2 cells, which can promote tumor growth, expanded. These immune changes create an environment that allows MM to persist and resist treatment. The findings suggest that therapies targeting NK-cell function and ILC balance could improve patient outcomes.

"Fifteen years of use of functional imaging in multiple myeloma: where we started and where we are going"

Source

Elena Zamagni, Marco Talarico; Fifteen years of use of functional imaging in multiple myeloma: where we started and where we are going. Blood Adv 2025; 9 (24): 6252–6266. doi: https://doi.org/10.1182/bloodadvances.2024015686  December 23, 2025.  

Overview

This review summarizes current knowledge on advanced imaging techniques used to detect and monitor bone disease in multiple myeloma (MM). 18F-FDG–PET/CT combines anatomical and metabolic information, making it the standard method for diagnosis, prognosis, and treatment response assessment, though it can occasionally give false-positive or false-negative results. Whole-body diffusion-weighted MRI (WB-DW-MRI) is a newer functional imaging approach that may detect more lesions, assess tumor burden, and better track response to therapy. Other techniques, like dynamic contrast-enhanced MRI and hybrid PET/MRI, offer complementary insights. Future developments may integrate artificial intelligence to improve accuracy and guide clinical decisions.

"Selinexor-based treatments are associated with increased expression of T-cell activation markers in multiple myeloma"

Source

Yubin Kang, Jadee L. Neff, Andrea Ellero, William R. Jeck, Cristina Gasparetto, Xiaobei Wang, Xufeng Chen, Zuowei Su, Christopher J. Walker; Selinexor-based treatments are associated with increased expression of T-cell activation markers in multiple myeloma. Blood Immunology & Cellular Therapy 2025; 1 (3): 100009. doi: https://doi.org/10.1016/j.bict.2025.100009  December  2025.  

Overview

This study explored how the multiple myeloma (MM) treatment selinexor (SEL) affects both cancer cells and the immune system in the bone marrow. Analysis of patient samples showed that higher levels of certain proteins in myeloma cells before treatment were linked to poorer outcomes, potentially serving as predictive markers. After treatment, T cells showed signs of activation without signs of exhaustion, suggesting SEL kills myeloma cells without impairing immune function. These findings suggest SEL may work well alongside immune therapies like CAR T cells or bispecific antibodies, highlighting its potential for combination strategies in MM.

"Evaluation of assumed tumour volume in multiple myeloma using dual-energy spectral CT and its correlation between haematological findings"

Source

Tetsuya Kosaka, Chisaki Masuda, Sachiho Tatebe, Risen Hirai, Akira Tanimura, Evaluation of assumed tumour volume in multiple myeloma using dual-energy spectral CT and its correlation between haematological findings, European Journal of Radiology Open, Volume 15, 2025,100675, ISSN 2352-0477, https://doi.org/10.1016/j.ejro.2025.100675. December 2025. 

Overview

This study tested whether dual-energy spectral CT (DESCT) can measure tumor volume in the upper arm (humerus) of multiple myeloma (MM) patients and whether these measurements reflect disease activity. Analysis of 22 patients showed that larger tumor volumes moderately correlated with higher β2-microglobulin levels, a marker of tumor burden. Tumor volume did not correlate with M-protein or free light chain levels. Changes in tumor volume over time mirrored changes in β2-microglobulin after treatment. These results suggest DESCT-based tumor volume could serve as a useful, noninvasive biomarker for monitoring MM.

"Toward Optimized Real-World Lymphodepletion in Idecabtagene Vicleucel (Ide-cel) Therapy: Lessons from Fludarabine Exposure in Multiple Myeloma"

Source

Dachy G, Poiré X. Toward Optimized Real-World Lymphodepletion in Idecabtagene Vicleucel (Ide-cel) Therapy: Lessons from Fludarabine Exposure in Multiple Myeloma. Transplant Cell Ther. 2025 Dec;31(12):948-951. doi: 10.1016/j.jtct.2025.11.014.  

Overview

This study highlights how the lymphodepletion regimen, specifically the drug fludarabine, influences both the safety and effectiveness of idecabtagene vicleucel (ide-cel) CAR T-cell therapy in patients with relapsed or refractory multiple myeloma. Lymphodepletion is given before CAR T-cell infusion to reduce the patient’s existing immune cells, allowing the CAR T cells to expand and work efficiently.

Using predicted fludarabine exposure from pharmacokinetic models, the study found that higher fludarabine exposure increased the risk of treatment-related toxicities, including cytokine release syndrome, neurotoxicity, prolonged low blood counts such as thrombocytopenia and neutropenia, and a higher risk of infections. Patients with higher exposure also required more interventions with corticosteroids and tocilizumab to manage these side effects.

These results suggest that fludarabine dosing is not uniform for all patients. Adjusting lymphodepletion based on individual pharmacokinetics could help minimize toxicities while preserving CAR T-cell efficacy, making this therapy safer for a broader range of patients, including those who are older or have additional health conditions.

"Knockdown of lncRNA NEAT1 suppresses multiple myeloma progression via the miR-133a-3p/ARPC5 axis"

Source

Xin Li, Peng Zhang, Zhenzhen Meng, Shanshan Luo, Knockdown of lncRNA NEAT1 suppresses multiple myeloma progression via the miR-133a-3p/ARPC5 axis, Journal of Radiation Research and Applied Sciences, Volume 18, Issue 4, 2025, 101878, ISSN 1687-8507, https://doi.org/10.1016/j.jrras.2025.101878. December 2025. 

Overview

This study investigated the role of the long non-coding RNA NEAT1 in multiple myeloma and identified a key molecular pathway through which it promotes disease progression. NEAT1 was found to be upregulated in patient samples and multiple myeloma cell lines, while miR-133a-3p was downregulated and ARPC5 expression was elevated. Functional experiments showed that increasing NEAT1 levels enhanced cell proliferation and invasion while reducing apoptosis, whereas NEAT1 knockdown had the opposite effect. Mechanistic studies revealed that NEAT1 acts by sponging miR-133a-3p, which normally suppresses ARPC5. Overexpression of ARPC5 reversed the tumor-suppressive effects of either NEAT1 knockdown or miR-133a-3p overexpression. In mouse models, NEAT1 depletion significantly reduced tumor growth. These results demonstrate that NEAT1 drives multiple myeloma progression through the miR-133a-3p/ARPC5 axis and suggest that targeting this pathway could represent a novel therapeutic approach.

"CAR-T cell therapy for multiple myeloma: An update on the current state and future potential"

Source

Prateek Pophali, Jacalyn Rosenblatt, David Avigan, CAR-T cell therapy for multiple myeloma: An update on the current state and future potential, Best Practice & Research Clinical Haematology, Volume 38, Issue 4, 2025, 101659, ISSN 1521-6926, https://doi.org/10.1016/j.beha.2025.101659. December 2025. 

Overview

This review examines the role of Chimeric Antigen Receptor T cell therapy in multiple myeloma, highlighting its development, mechanism of action, and clinical impact. CAR-T therapy involves genetically engineering a patient’s T cells to express a receptor targeting a tumor-associated antigen, commonly B-cell maturation antigen in multiple myeloma. These modified T cells can recognize and kill myeloma cells through multiple mechanisms, including cytotoxic molecule release, apoptosis induction, and activation of other immune cells. While CAR-T therapy has shown dramatic efficacy, most patients eventually experience disease progression due to CAR-T cell exhaustion, antigen-negative tumor variants, or the immunosuppressive tumor microenvironment. Approved products have demonstrated effectiveness even in earlier relapse, but their use carries unique toxicities such as cytokine release syndrome, neurotoxicity, cytopenias, hypogammaglobulinemia, and infection risk. Research continues to optimize CAR-T cell constructs, improve persistence, reduce toxicity, and explore novel targets to enhance therapeutic outcomes in multiple myeloma.

"The effects of geranylgeranyl diphosphate synthase inhibitor treatment on osteoblast biology and application in a conditioned media model of myeloma bone disease"

Source

Molly E. Muehlebach, Sarah A. Holstein, The effects of geranylgeranyl diphosphate synthase inhibitor treatment on osteoblast biology and application in a conditioned media model of myeloma bone disease, Bone Reports, Volume 27, 2025, 101874, ISSN 2352-1872, https://doi.org/10.1016/j.bonr.2025.101874. December 2025. 

Overview

This study investigated the effects of the geranylgeranyl diphosphate synthase inhibitor RAM2061 on myeloma bone disease, a condition characterized by tumor-driven osteoclast activation and suppression of osteoblast function. RAM2061, a novel targeted therapy, has previously shown direct anti-myeloma activity and anti-osteoclastic effects. In this study, exposure of osteoblast precursors to RAM2061 or zoledronic acid impaired osteoblast differentiation and mineralization, while mature osteoblasts were largely unaffected. Under conditions simulating the myeloma bone microenvironment using myeloma cell–conditioned media, RAM2061 preserved anti-resorptive activity and inhibited osteoblast differentiation in precursors, but not in differentiated cells. These findings clarify the drug’s bone-specific effects and support further investigation of GGSIs as a therapeutic strategy for myeloma bone disease.

"NK92 cells stably transfected with CD16 are efficient against multiple myeloma cells ex vivo and in vivo, especially if combined with daratumumab"

Source

Giraldos, D., Galano-Frutos, E., Cambronero-Arregui, L., Beltrán Visiedo, M., Romanos, E., Reina-Ortiz, C., … Anel, A. (2025). NK92 cells stably transfected with CD16 are efficient against multiple myeloma cells ex vivo and in vivo, especially if combined with daratumumab. OncoImmunology, 14(1). https://doi.org/10.1080/2162402X.2025.2559782  December 2025. 

Overview

This study evaluated a combination approach using the anti-CD38 monoclonal antibody daratumumab with natural killer (NK) cells to enhance antibody-dependent cell-mediated cytotoxicity against multiple myeloma. Initially, expanded and activated NK cells demonstrated significant cytotoxicity against myeloma cell lines. To overcome donor variability and enhance efficacy, the NK92 cell line was used, which exhibited stronger cytotoxic activity but lacked the CD16 receptor required for antibody-mediated activity. Transfection of NK92 cells with CD16 generated a stable NK92-CD16 line, which, when combined with daratumumab, showed potent anti-myeloma activity in both 2D and 3D cultures and against patient-derived plasma cells, including relapsed disease. In vivo experiments confirmed tumor regression and near-complete elimination of myeloma cells when NK92-CD16 cells were combined with daratumumab, supporting the therapeutic potential of this strategy.

"NPM1 mediated up – regulation of CXCR4 might drive bortezomib resistance in multiple myeloma"

Source

Shi, Y., Deng, Y., Ma, J., Li, Y., Ji, T., Tao, H., … Yu, L. (2025). NPM1 mediated up – regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2565956  December 2025. 

Overview

This study investigated the mechanisms underlying bortezomib resistance in multiple myeloma. Analysis of gene expression data identified NPM1 as a key hub gene associated with poor survival and lower response rates to bortezomib-containing regimens. In bortezomib-resistant myeloma cells, NPM1 expression was significantly higher than in parental cells. Knockdown of NPM1 or treatment with the NPM1 inhibitor NSC348884 restored sensitivity to bortezomib. Mechanistic studies indicated that NPM1 promotes resistance by upregulating CXCR4 expression at both transcriptional and translational levels. These findings suggest that NPM1 could serve as a prognostic biomarker and a potential therapeutic target to overcome bortezomib resistance in multiple myeloma.

"Adaptive designs in randomized clinical trials: reanalysis of the HOVON87/NMSG18 multiple myeloma trial"

Source

Maarten R. Seefat, Niek G. van der Maas, Kazem Nasserinejad, Bronno van der Holt, Anders Waage, Ulf-Henrik Mellqvist, Annette Juul Vangsted, Anna J.T. Smit, Febe Smits, Paula F. Ypma, Niels W.C.J. van de Donk, Hedwig M. Blommestein, Jan J. Cornelissen, David G.J. Cucchi, Sonja Zweegman, Jurjen Versluis, Adaptive designs in randomized clinical trials: reanalysis of the HOVON87/NMSG18 multiple myeloma trial, eClinicalMedicine, Volume 90, 2025, 103605, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2025.103605.  December 2025. 

Overview

This study evaluated whether adaptive trial designs could improve efficiency and decision-making in multiple myeloma clinical trials. Using data from the phase III HOVON87/NMSG18 trial, which did not meet its primary endpoint, the researchers retrospectively modeled two adaptive designs: group sequential and sample size re-estimation. The group sequential design generally recommended continuation, though the more aggressive Pocock spending function suggested early termination for futility at the second interim analysis. Sample size re-estimation indicated no expansion was needed. These results suggest adaptive designs can detect futility earlier, potentially reducing follow-up time, limiting patient exposure to ineffective treatments, and enhancing trial efficiency.

"Dual targeting of BCMA and B7-H3 with CAR T cells and bispecific protein engagers enhances anti-myeloma activity"

Source

Naeramit Sontayananon, Pornpimon Yuti, Nunghathai Sawasdee, Seiji Okada, Mutita Junking, Jatuporn Sujjitjoon, Pa-Thai Yenchitsomanus, Dual targeting of BCMA and B7-H3 with CAR T cells and bispecific protein engagers enhances anti-myeloma activity, Biomedicine & Pharmacotherapy, Volume 193, 2025, 118820, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2025.118820. December 2025. 

Overview

This study investigated a dual-targeting approach for relapsed or refractory multiple myeloma using BCMA-directed CAR T cells combined with a B7-H3/CD3 bispecific protein engager (BiPE). In vitro experiments showed that the combination enhanced cytotoxicity against both BCMA+/B7-H3high and BCMA+/B7-H3low myeloma cells, outperforming either therapy alone, particularly at low effector-to-target ratios. Co-treatment increased T cell activation, proliferation, effector memory differentiation, and secretion of key cytotoxic molecules and cytokines. Although BiPE initially induced transient upregulation of exhaustion markers, central memory T cell phenotypes were preserved upon tumor re-challenge. This strategy may overcome resistance and offers a promising therapeutic option for BCMA+/B7-H3+ multiple myeloma.