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 January 2026 edition.

The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.

In the Journals (Key Myeloma Research in January 2026)

"Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma"

Source

Zhibo Yan, Zhannan Han, Yihui Wang, Maja Beus, Yu Zhang, Alfredo Picado, Carrow I. Wells, Jian Wu, Loren B. Weidenhammer, Karla M. Pires, Elizabeth A. Leibold, Liang Liu, David M. Gooden, Ivan Spasojevic, Erik J. Soderblom, Yubin Kang, Lawrence H. Boise, Timothy M. Willson, Mikhail A. Nikiforov; Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma. Blood 2026; 147 (1): 48–60. doi: https://doi.org/10.1182/blood.2025029950  January 1, 2026. 

Overview

Researchers in this study looked at why multiple myeloma cells are able to survive and resist treatment. They focused on ferroptosis, a natural form of cell death that depends on iron and damage to cell membranes. In healthy cells, ferroptosis helps remove damaged or dangerous cells, but myeloma cells often block this process. The researchers identified a protein called STK17B that plays a key role in shutting ferroptosis down. They found that STK17B levels are higher in people with relapsed myeloma and are linked to shorter survival. When STK17B was blocked in myeloma cells, iron levels increased, cell damage rose, and the cancer cells became more sensitive to standard treatments. In mouse models, an oral drug that inhibits STK17B triggered ferroptosis and slowed tumor growth. These findings suggest that targeting STK17B could help overcome drug resistance and improve future myeloma treatments.

"Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis"

Source

Wang, J., Zi, F., Liu, W., Liu, C., Zhang, Z., Kong, L., … Li, J. (2026). Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis. Gut Microbes, 18(1). https://doi.org/10.1080/19490976.2025.2609455 January 2, 2026. 

Overview

This study explored how gut bacteria may influence multiple myeloma and whether changing the microbiome could help slow the disease. Researchers found that people with myeloma had fewer beneficial gut bacteria that produce butyrate, a fatty acid important for immune health, and lower butyrate levels overall compared with healthy individuals. When gut bacteria from healthy donors were transferred into myeloma mouse models, tumor growth decreased and butyrate levels increased. The researchers identified a specific bacterium, Clostridium butyricum, as a key source of butyrate. Giving this bacterium or butyrate itself reduced tumor burden, lowered inflammation in the bone marrow, and protected against bone damage by reducing harmful immune signals. Butyrate also directly triggered cancer cell death by shutting down survival pathways inside myeloma cells. Together, these findings support the idea that probiotic-based approaches could one day complement myeloma treatment.

"Inconsistent definitions of transplant ineligibility in multiple myeloma: A systematic review"

Source

Neupane K, Singstock M, Shah D, Dahal R, Mian H, Smith F, et al. Inconsistent definitions of transplant ineligibility in multiple myeloma: A systematic review. Br J Haematol. 2026; 00: 1–8. https://doi.org/10.1111/bjh.70323  January 2, 2026. 

Overview

High-dose melphalan followed by an autologous stem cell transplant is a standard treatment for many people newly diagnosed with multiple myeloma, but not everyone is healthy enough to receive it. This review looked at clinical trials involving patients considered ineligible for transplant and found that there is no clear or consistent way to define who falls into this group. Fewer than half of the studies clearly explained why patients were considered transplant ineligible, and many relied mainly on age, often using 65 as a cutoff. Important factors such as other health conditions, physical function, and frailty were often missing or poorly described. Because of these differences, it can be difficult to compare study results or apply them confidently to patient care. The findings highlight the need for clearer, evidence-based guidelines to define transplant ineligibility in multiple myeloma.

"Elevated non-clonal bone marrow plasma cell fraction at diagnosis is associated with improved outcomes in multiple myeloma"

Source

Zanwar, S., Jevremovic, D., Kapoor, P. et al. Elevated non-clonal bone marrow plasma cell fraction at diagnosis is associated with improved outcomes in multiple myeloma. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-025-01449-9 January 3, 2026. 

Overview

This study looked at whether a specific immune-related feature in the bone marrow could help predict outcomes for people newly diagnosed with multiple myeloma. Researchers focused on the proportion of healthy, non-cancerous plasma cells compared with total plasma cells at diagnosis. About 16% of patients had higher levels of these normal plasma cells. These patients tended to have less cancer in the bone marrow and more favorable disease features, while receiving similar treatments as others. Importantly, they lived longer and stayed in remission longer than patients with lower levels of normal plasma cells. This survival benefit remained even after accounting for other known risk factors. The findings suggest that measuring normal plasma cells at diagnosis may provide useful additional information about prognosis and could become a new tool to help guide care in multiple myeloma.

"Optical Genome Mapping for Cytogenetic Analysis in Multiple Myeloma: Real-World Evidence"

Source

S. Liang, G. Tang, M. Klausner, et al., “Optical Genome Mapping for Cytogenetic Analysis in Multiple Myeloma: Real-World Evidence,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70175.  January 4, 2026.  

Overview

This letter describes a study evaluating a newer genetic testing method called optical genome mapping (OGM) in multiple myeloma. Genetic changes in myeloma cells are important because they help doctors estimate risk and guide treatment, but standard tests such as FISH and karyotyping have limits and can miss important abnormalities. The researchers compared OGM with these standard methods in samples from over 200 patients. They found that OGM detected far more genetic changes, including many high-risk and complex abnormalities that standard tests often failed to identify. OGM also worked well even when other tests produced normal or unclear results, as long as enough myeloma cells were present in the sample. Overall, the study suggests that OGM could provide a more complete picture of a patient’s myeloma genetics and may improve how the disease is diagnosed and classified in the future.

"Efficacy and safety of teclistamab in triple-class-exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort"

Source

Martin TG, Mateos M-V, Yi JH, et al. Efficacy and safety of teclistamab in triple-class-exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort. Cancer. 2026;e70237. doi:10.1002/cncr.70237  January 4, 2026. 

Overview

This study evaluated the real-world and clinical trial performance of teclistamab, a targeted immune therapy approved for people with relapsed or refractory multiple myeloma who have already received several prior treatments. Researchers analyzed results from global clinical trials and from patients treated in Asia, both within and outside of trials. Across all groups, most patients had heavily treated disease and many had high-risk features. Teclistamab led to high response rates, with many patients achieving deep responses that lasted for a long time. Survival outcomes were encouraging and remained strong with extended follow-up, including in Asian patients who generally had lower body weight. The main side effects included low blood counts, cytokine release syndrome, and infections, which became easier to manage over time. Overall, the findings support teclistamab as an effective and reliable treatment option for patients with advanced multiple myeloma.

"The role of immune cells in multiple myeloma: a bidirectional Mendelian randomization study"

Source

Xu, P., Wang, Y., Hu, Y., & Li, Z. (2026). The role of immune cells in multiple myeloma: a bidirectional Mendelian randomization study. Hematology, 31(1). https://doi.org/10.1080/16078454.2025.2611692  January 5, 2026. 

Overview

This study examined whether specific immune cell traits may play a direct role in the development of multiple myeloma. Using large genetic datasets from European populations, the researchers applied a method that helps test cause-and-effect relationships rather than simple associations. They analyzed hundreds of immune cell features to see whether genetic differences linked to immune function were also linked to myeloma risk. A small number of immune traits showed possible connections to myeloma, but these findings did not meet the strictest standards for statistical certainty. The results also suggested that multiple myeloma itself may weaken or disrupt normal immune cell function. While the findings are early and need confirmation in larger studies, they provide new insight into how the immune system and myeloma may influence each other and could help guide future research on immune-based treatments.

"Myeloid-Derived Suppressor Cells (MDSCs) Suppress T-Cell Proliferation Less Than Mature Neutrophils in Blood and Bone Marrow From Multiple Myeloma Patients"

Source

Westerlund, Julia, Askman, Sandra, Pettersson, Åsa, Wichert, Stina, Hellmark, Thomas, Johansson, Åsa C. M., Hansson, Markus, Myeloid-Derived Suppressor Cells (MDSCs) Suppress T-Cell Proliferation Less Than Mature Neutrophils in Blood and Bone Marrow From Multiple Myeloma Patients, Journal of Immunology Research, 2026, 9232540, 11 pages, 2026. https://doi.org/10.1155/jimr/9232540  January 5, 2026. 

Overview

This study explored whether a group of immune cells called myeloid-derived suppressor cells, or MDSCs, play an important role in multiple myeloma or its early stage, MGUS. MDSCs are known to weaken immune responses in many cancers and are often linked to worse outcomes. Researchers examined different types of MDSCs in the blood and bone marrow of people with MGUS and multiple myeloma and compared them with each other. They found that MDSC levels were not higher in either condition and that these cells showed little ability to block T-cell activity. One MDSC subtype was even lower in the blood of patients with multiple myeloma. In contrast, mature neutrophils showed a stronger ability to suppress immune responses. These results suggest that MDSCs may not be major drivers of myeloma, while other immune cells may play a more important role.

"Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells"

Source

Sabol, H.M., Paxton, B.C., Anloague, A. et al. Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells. J Exp Clin Cancer Res (2026). https://doi.org/10.1186/s13046-025-03630-1  January 5, 2026.  

Overview

This study investigated why multiple myeloma often comes back after treatment, even when therapies initially work well. Researchers focused on two hard-to-treat cell populations: actively growing cancer cells that resist drugs and dormant myeloma cells that can survive quietly and cause relapse later. By analyzing patient data and laboratory models, they found that both types of cells rely on the same survival pathway, known as Notch signaling, particularly a protein called NOTCH3. Higher activity of this pathway was linked to worse outcomes in newly diagnosed patients. When the researchers blocked NOTCH3 or broadly inhibited Notch signaling in preclinical models, tumor growth decreased and both resistant and dormant cells were eliminated. These findings suggest that targeting NOTCH3 could be a new strategy to reduce relapse and achieve longer-lasting control of multiple myeloma.

"Multiple myeloma risk linked to DNA damage response genes."

Source

Conry, M., Ostrovnaya, I., Kemel, Y. et al. Multiple myeloma risk linked to DNA damage response genes. J Hematol Oncol (2026). https://doi.org/10.1186/s13045-025-01776-1  January 6, 2026.  

Overview

This study examined whether inherited changes in genes involved in repairing DNA may increase the risk of developing multiple myeloma. By comparing genetic data from thousands of people with myeloma and cancer-free individuals, the researchers found that rare inherited mutations in several DNA repair genes were linked to a higher risk of the disease. These genetic changes were more common in people who developed myeloma at a younger age or who had a family history of the condition. Certain mutations, particularly in TP53 and ATM, were also associated with shorter survival. The findings suggest that some inherited DNA repair genes play a role in myeloma risk and outcomes. Identifying these genetic changes could help pinpoint people at higher risk and support earlier monitoring or screening in families affected by plasma cell disorders.

"Barriers to and Facilitators of Clinical Trial Participation in Multiple Myeloma. Blood Global Hematology 2026"

Source

Martin Kaiser, Saba Ul-Hasan, Jack Lewis, Federica Mirto, Alicia O’Neill, Yelak Biru, Cynthia Chmielewski, Katie Joyner, Elise Gamertsfelder; Barriers to and Facilitators of Clinical Trial Participation in Multiple Myeloma. Blood Global Hematology 2026; 100056. doi: https://doi.org/10.1016/j.bglo.2025.100056  January 6, 2026. 

Overview

This study looked at why people with multiple myeloma are not equally represented in clinical trials and how this affects access to new treatments. The researchers found that most trials over the past decade were concentrated in the US and parts of Europe and Asia, leaving other regions underrepresented. They also identified common barriers that prevent patients from joining trials, including strict eligibility rules, socioeconomic challenges, lack of physician awareness, and regulatory hurdles. By consulting stakeholders worldwide, the study highlighted strategies that could improve enrollment and make trials more accessible globally. Addressing these barriers could help ensure that patients everywhere have the opportunity to benefit from experimental therapies and that research results better reflect the diversity of the myeloma population.

"Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline"

Source

Lisa K. Hicks et al. Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline. J Clin Oncol 0, JCO-25-02587 DOI:10.1200/JCO-25-02587 January 6, 2026. 

Overview

The ASCO guidelines provide updated recommendations for treating multiple myeloma based on a thorough review of the latest research. For patients with high-risk smoldering myeloma, daratumumab may be offered. For those eligible for a stem cell transplant, initial therapy should include a four-drug combination—either daratumumab or isatuximab with bortezomib, lenalidomide, and dexamethasone—followed by maintenance therapy with at least lenalidomide, with additional agents like daratumumab, carfilzomib, or dexamethasone as appropriate. Transplant-ineligible patients can also receive the same quadruplet therapy if suitable. For patients whose disease has returned or is resistant to prior treatments, triplet therapy or T-cell redirecting therapies are recommended based on established principles. These guidelines aim to support clinicians in making informed treatment decisions while considering patient-specific factors.

"Belantamab mafodotin, pomalidomide, and dexamethasone in Japanese patients with RRMM in the phase 3 DREAMM-8 trial"

Source

Sunami, K., Handa, H., Ichii, M. et al. Belantamab mafodotin, pomalidomide, and dexamethasone in Japanese patients with RRMM in the phase 3 DREAMM-8 trial. Int J Hematol (2026). https://doi.org/10.1007/s12185-025-04150-6 January 6, 2026. 

Overview

This phase 3 study looked at how well a three-drug combination of belantamab mafodotin, pomalidomide, and dexamethasone (BPd) works compared with bortezomib, pomalidomide, and dexamethasone (PVd) in Japanese patients whose multiple myeloma had returned after prior lenalidomide treatment. In this small group of 21 patients, BPd showed strong results: 90% of patients responded to treatment compared with 73% for PVd, and more patients achieved very deep responses. Progression-free survival was longer with BPd, and the duration of response was also promising. Side effects were generally manageable, although eye-related issues were more common with BPd, most of which were temporary and reversible. Overall, these results suggest that BPd is an effective and tolerable option for Japanese patients with relapsed or refractory multiple myeloma.

"Peripheral blood immune cell profiling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma"

Source

Pandey, T., Mohan Lal, B., Alrawabdeh, J. et al. Peripheral blood immune cell profiling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma. Blood Cancer J. 16, 4 (2026). https://doi.org/10.1038/s41408-025-01443-1  January 6, 2026. 

Overview

This study examined whether the makeup of a patient’s immune cells before receiving BCMA CAR-T therapy could predict how well they would respond in relapsed or refractory multiple myeloma. Researchers analyzed 110 patients and measured different types of T cells, B cells, and natural killer cells before apheresis and lymphodepletion. They found that patients with a low CD4+/CD8+ ratio or elevated CD8+ suppressor/cytotoxic T cells before treatment, as well as low B cell levels prior to lymphodepletion, were less likely to respond to therapy by day 90. These findings suggest that certain pre-treatment immune patterns may indicate a higher risk of poor response and could help guide patient selection or the use of combination strategies to improve outcomes. While the study provides the largest dataset to date on this topic, further research is needed to confirm these results and explore ways to modify immune profiles before CAR-T therapy to optimize effectiveness.

"A bortezomib resistance–related gene signature predicts prognosis, with ARID5B downregulation associated with poor overall survival in multiple myeloma"

Source

Ding, Y., Xiao, M., Zhu, J. et al. A bortezomib resistance–related gene signature predicts prognosis, with ARID5B downregulation associated with poor overall survival in multiple myeloma. Discov Onc (2026). https://doi.org/10.1007/s12672-026-04383-9  January 6, 2026. 

Overview

This study investigated genes linked to resistance to the drug bortezomib in multiple myeloma (MM) to see if they could help predict patient outcomes. Researchers analyzed gene expression in bortezomib-resistant myeloma cells and patient data, identifying five key genes—IFI16, ARID5B, LTBP1, PNOC, and CRIP1—that together form a “bortezomib resistance” signature. This signature reliably stratified patients by risk and independently predicted overall survival. Patients with lower ARID5B levels had worse outcomes, while high-risk patients based on the gene signature may respond better to alternative chemotherapy such as doxorubicin or etoposide. These findings suggest that BRG profiling could guide treatment decisions and identify patients at higher risk of poor prognosis.

"After CAR-T therapy for myeloma: challenge of persistent cytopenias and infections"

Source

Beyar-Katz O, Stern A. After CAR-T therapy for myeloma: challenge of persistent cytopenias and infections. Haematologica 2026;111(1):86-88; https://doi.org/10.3324/haematol.2025.288539.  January 2026. 

Overview

This study reviewed real-world data on cilta-cel, a CAR T-cell therapy for relapsed/refractory multiple myeloma (MM), focusing on long-term hematologic and infectious complications. Among patients treated outside clinical trials, over half experienced severe cytopenias at day 30 post-infusion, with nearly one-quarter persisting at day 90. Risk factors included extramedullary disease, high-risk cytogenetics, prior therapies, baseline cytopenias, high CAR-HEMATOTOX scores, and tocilizumab use. Infections affected nearly half of patients, with severe cases in up to one-third, shifting from bacterial early to viral later, reflecting evolving immune vulnerabilities. Supportive measures, including stem cell boosts, were effective for cytopenia recovery. The findings highlight the need for proactive monitoring, risk stratification, and multidisciplinary care to manage prolonged cytopenias, infection risk, and immune dysfunction after cilta-cel therapy, ensuring safer implementation of this transformative MM treatment.

"Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial"

Source

Korst, Charlotte L B M et al. Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial. The Lancet Haematology, Volume 13, Issue 1, e30 – e40.  https://doi.org/10.1016/S2352-3026(25)00298-4  January 2026. 

Overview

This phase 2 ICON study evaluated iberdomide combined with low-dose cyclophosphamide and dexamethasone (IberCd) in 61 patients with relapsed/refractory multiple myeloma who had received 2–4 prior therapies. Patients were heavily pretreated, with 85% triple-class exposed and 44% triple-class refractory. After a median follow-up of 25.4 months, median progression-free survival was 17.6 months. The most common grade 3–4 adverse events were neutropenia (56%) and infections (34%), with serious treatment-related events in 41% of patients. IberCd demonstrated clinically meaningful activity as an all-oral regimen, providing an effective treatment option for patients with relapsed/refractory multiple myeloma.

"The role of cytokines in immune cell-mediated multiple myeloma and the identification of therapeutic targets"

Source

Chao Wang, Yi Cai, Jie Jie, The role of cytokines in immune cell-mediated multiple myeloma and the identification of therapeutic targets, Cytokine, Volume 197, 2026, 157075, ISSN 1043-4666, https://doi.org/10.1016/j.cyto.2025.157075. January 2026. 

Overview

This study used two-step Mendelian randomization and Summary-data-based MR analyses to investigate causal links between immune cell subtypes, cytokines, and multiple myeloma (MM). The results identified 20 immune cell subtypes and three cytokines with causal effects on MM, with SLAM mediating 9.16% of the effect of CD4+ cells. SMR analysis highlighted CD4+ and naive CD4+ cells as potential therapeutic targets, and inhibiting the KIT gene may enhance CD4+ T cell antitumor activity. These findings offer new insights into MM pathophysiology and support the development of immune-targeted therapies.

"National multiple myeloma cohort: Gaps and opportunities for research in Brazil"

Source

Diogo Moreira do Amaral, National multiple myeloma cohort: Gaps and opportunities for research in Brazil, Hematology, Transfusion and Cell Therapy, Volume 48, Issue 1, 2026, 106229, ISSN 2531-1379, https://doi.org/10.1016/j.htct.2025.106229. Jan-March 2026. 

Overview

This letter reviews a 16-year Brazilian cohort study of 25,370 multiple myeloma (MM) patients treated within the public health system (SUS). The analysis highlights a median patient age of 62 years, male predominance, regional disparities, and overall survival (OS) of 37 months. Access to innovative therapies and hematopoietic stem cell transplantation (HSCT) was associated with markedly improved outcomes, with OS reaching 67 months for bortezomib-treated patients and 87 months for those receiving HSCT. However, only 26.9% underwent transplantation, reflecting structural barriers and late incorporation of new drugs. The study emphasizes the need for equitable access to therapies, expansion of transplantation centers, and robust population-based data to guide health policy in Brazil.

"Mechanistic insights into the antiproliferative effect of the redox-active iron chelator Dp44mT on multiple myeloma cell lines"

Source

Aarti Sharma, Latha Pathangey, Sinto Sebastian Chirackal, Kiran K. Mangalaparthi, Akhilesh Pandey, Rafael Fonseca, Sundararaman Swaminathan, Mechanistic insights into the antiproliferative effect of the redox-active iron chelator Dp44mT on multiple myeloma cell lines, Hematology, Transfusion and Cell Therapy, Volume 48, Issue 1, 2026, 106233, ISSN 2531-1379, https://doi.org/10.1016/j.htct.2025.106233. Jan-March 2026. 

Overview

This study investigated the anti-myeloma potential of the redox-active iron chelator Dp44mT. Using both drug-sensitive and drug-resistant multiple myeloma cell lines, the researchers demonstrated that Dp44mT potently reduced cell viability. Mechanistic analyses revealed that its effects are linked to disrupted iron metabolism, altered reactive oxygen species homeostasis, and mitochondrial dysfunction. Proteomic and phosphoproteomic profiling highlighted involvement of the AMPK pathway, cell cycle regulation, endoplasmic stress, and downregulation of ACSL4. These findings suggest that Dp44mT exerts in vitro anti-myeloma activity through multiple interconnected pathways, supporting its potential as a therapeutic agent for further investigation.

"Prevalence and Survival Impact of Venous and Arterial Thrombosis among Multiple Myeloma Patients in Single Tertiary Care Center of Thailand: 5-Year Retrospective Review"

Source

Hongtongsagool, P., Teawtrakul, N., Wanitpongpun, C. et al. Prevalence and Survival Impact of Venous and Arterial Thrombosis among Multiple Myeloma Patients in Single Tertiary Care Center of Thailand: 5-Year Retrospective Review. Indian J Hematol Blood Transfus 42, 66–72 (2026). https://doi.org/10.1007/s12288-024-01938-0  January 2026. 

Overview

This study looked at blood clots in Thai patients who were newly diagnosed with multiple myeloma, a type of blood cancer. Blood clots can happen in veins or arteries and are known to increase health risks, but there has been limited information about how often they occur in Thai patients. Researchers followed 146 patients treated at a large hospital in Thailand between 2018 and 2022. They found that a small number of patients developed symptoms from blood clots. About 8 out of every 100 patients had clots in their veins, about 1 out of 100 had clots in their arteries, and fewer than 1 out of 100 had both. Overall, blood clots were less common than expected in this group.

The study also examined whether having a blood clot affected how long patients lived. After three years, survival rates were similar for patients who had blood clots and those who did not, showing no clear difference in overall survival. Researchers also found that patients who received preventive treatment to reduce clot risk were much less likely to develop blood clots. Importantly, this prevention did not increase the risk of bleeding. In summary, blood clots were relatively uncommon in Thai patients with multiple myeloma, preventive treatment helped lower clot risk safely, and having a blood clot did not appear to shorten survival in this group.

"Second Primary Malignancies Post Autologous Stem-cell Transplant in Multiple Myeloma from India – Knowing the Unknown"

Source

Mirgh, S., Surendran, A., Punatar, S. et al. Second Primary Malignancies Post Autologous Stem-cell Transplant in Multiple Myeloma from India – Knowing the Unknown. Indian J Hematol Blood Transfus 42, 243–249 (2026). https://doi.org/10.1007/s12288-025-01984-2  January 2026. 

Overview

This study examined how often second cancers develop in people with multiple myeloma after they receive an autologous stem cell transplant, a treatment that uses the patient’s own stem cells. Researchers reviewed records from a long-term database of patients who had transplants between 2007 and 2022. In total, 178 patients underwent 192 transplants, with a small number of patients receiving a second transplant. The researchers collected information on patient characteristics, treatments before and after transplant, and any cancers that developed later, along with how those cancers were treated and the outcomes.

Over time, six patients, or about 3 out of every 100, developed a second, unrelated cancer. Half of these were solid tumors and half were blood-related cancers. These second cancers appeared many years after the original myeloma diagnosis and transplant, usually around 8 to 9 years later. All six patients had been treated with lenalidomide, a common myeloma medication, for about two years on average before the second cancer was diagnosed. At the time of reporting, three of the six patients were still alive. Overall, second cancers were uncommon but did occur long after transplant, showing that people with multiple myeloma need lifelong follow-up after stem cell transplant to watch for new cancers.

"Hematopoietic stem cell transplantation for multiple myeloma in Kazakhstan: Ten-year single-center experience"

Source

Kemaykin V, Burkitbayev Z, Karabekov A, Kolesnikova O, Zhakhina G, Saparbay J, Vildanova R, Idrisova A, Zharlyganova D, Kuanysh Z. Hematopoietic stem cell transplantation for multiple myeloma in Kazakhstan: Ten-year single-center experience. J Int Med Res. 2026 Jan;54(1):3000605251411783. doi: 10.1177/03000605251411783. Epub 2026 Jan 23. 

Overview

This study looked at how multiple myeloma has been treated and how patients have done over time at a major cancer center in Kazakhstan. Researchers reviewed medical records from 261 patients who were treated between 2010 and 2021. Most patients were diagnosed at stage II of the disease and were around 54 years old on average, which suggests that multiple myeloma may start at a younger age in this population compared with other countries. The most common first treatment was a combination of bortezomib and dexamethasone.

Nearly half of the patients went on to receive a stem cell transplant. These patients lived longer on average than those who were treated with chemotherapy alone. Five years after treatment, about 64 out of 100 patients who had a transplant were still alive, compared with about 46 out of 100 patients who did not have a transplant. The study found that treatment choices, how well stem cells were collected, and problems after transplant all affected survival. These results highlight the importance of improving access to stem cell transplant and supportive care to improve outcomes for people with multiple myeloma in Kazakhstan.

"Long-term follow-up of zevor-cel in patients with relapsed/refractory multiple myeloma"

Source

Chengcheng Fu, Wenming Chen, Zhen Cai, Lingzhi Yan, Huijuan Wang, Jingjing Shang, Yin Wu, Shuang Yan, Wen Gao, Xiaolan Shi, Xiaoyan Han, Fang Tang, Gaofeng Zheng, Yanling Wen, Xingxing Meng, Daijing Yuan, Huamao Wang, Zonghai Li; Long-term follow-up of zevor-cel in patients with relapsed/refractory multiple myeloma. Blood Adv 2026; 10 (2): 468–478. doi: https://doi.org/10.1182/bloodadvances.2025017365  January 27, 2026.  

Overview

This study looked at a new type of immune therapy for people with relapsed or refractory multiple myeloma, meaning their cancer had returned or stopped responding to treatment. These patients often have poor outcomes because the disease becomes resistant to drugs. The treatment studied was zevorcabtagene autoleucel, also called zevor-cel, which is a CAR T-cell therapy. CAR T-cell therapy works by collecting a patient’s own immune cells, reprogramming them in a lab to recognize myeloma cells, and then giving them back to the patient. The study took place in China and included 14 patients who had already received at least three previous treatments.

After a single infusion of zevor-cel, nearly all patients had mild to moderate side effects related to immune activation, called cytokine release syndrome, but no serious brain-related side effects or long-term safety problems were seen. Importantly, none of the deaths that occurred during follow-up were linked to the treatment. All patients responded to therapy, and most had a deep response, with nearly 8 out of 10 achieving a complete response or better. Many responses lasted for years, and more than 4 out of 10 patients still had disease control three years after treatment. Survival rates remained high over time, with about 77 out of 100 patients still alive five years after infusion. Overall, this long-term follow-up shows that zevor-cel had strong and lasting effects with a manageable safety profile in heavily treated patients with multiple myeloma.

"CD56 negativity is associated with worse survival outcomes in patients with multiple myeloma: a meta-analysis"

Source

Zhu, G., Zhu, S., Yang, F. et al. CD56 negativity is associated with worse survival outcomes in patients with multiple myeloma: a meta-analysis. World J Surg Onc (2026). https://doi.org/10.1186/s12957-026-04220-x  January 23, 2026. 

Overview

This study reviewed existing research to understand whether a protein called CD56 can help predict outcomes in people with multiple myeloma. CD56 is found on the surface of some myeloma cells, but its role in predicting survival has been unclear. Researchers combined results from 22 studies that included nearly 2,800 patients to see how CD56 status related to how long patients lived and how long their disease stayed under control.

The analysis showed that patients whose myeloma cells did not have CD56 tended to have worse outcomes. These patients were about twice as likely to die sooner and were more likely to have their disease worsen earlier compared with patients whose cells did have CD56. The link between CD56 and shorter survival was strongest in studies from Asian countries, while this pattern was not seen as clearly in studies from other regions. However, CD56-negative patients had shorter periods without disease progression regardless of where the study was done. Overall, the findings suggest that lack of CD56 may be a useful marker for identifying patients at higher risk, especially in Asian populations, and could help guide more personalized treatment decisions.

"Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone"

Source

Luca Bertamini, Cathelijne Fokkema, Paula Rodriguez-Otero, Mark van Duin, Evangelos Terpos, Mattia D’Agostino, Vincent H. J. van der Velden, Niels W. C. J. van de Donk, Michel Delforge, Christoph Driessen, Roman Hajek, Hermann Einsele, Annette Vangsted, Diego Vieyra, Ricardo Attar, Anna Sitthi-Amorn, Robin Carson, Fredrik Schjesvold, Pawel Robak, Meral Beksac, Andrew Spencer, Annemiek Broijl, Tom Cupedo, Philippe Moreau, Mario Boccadoro, Pieter Sonneveld; Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. Blood 2026; 147 (4): 431–442. doi: https://doi.org/10.1182/blood.2025030113  January 22, 2026.  

Overview

This study looked at whether circulating tumor cells, which are myeloma cells found in the blood, can help predict outcomes in people newly diagnosed with multiple myeloma who are healthy enough to receive a stem cell transplant. While circulating tumor cells are known to signal higher risk in general, their role had not been clear in patients treated with modern four-drug therapy that includes daratumumab. Researchers analyzed data from a large international clinical trial that compared two treatment approaches, both followed by stem cell transplant. One group received daratumumab combined with bortezomib, lenalidomide, and dexamethasone, while the other group received the same treatment without daratumumab.

Blood samples from 451 patients were tested, and most patients had detectable circulating tumor cells at diagnosis. Higher levels of these cells were linked to a greater chance that the disease would come back sooner, regardless of other risk factors. Patients with lower levels of circulating tumor cells did especially well when treated with the daratumumab-containing regimen, with more patients remaining free of disease progression four years after treatment compared with those who did not receive daratumumab. Patients with higher levels of circulating tumor cells were less likely to achieve very deep responses, but daratumumab still improved response rates in both high- and low-risk groups. Overall, the study shows that circulating tumor cells are an important marker of risk in newly diagnosed patients and that adding daratumumab improves treatment responses, even in patients with higher-risk disease.

"Diagnosis, risk stratification and management of smouldering multiple myeloma"

Source

Zanwar, S., Kumar, S. & Rajkumar, S.V. Diagnosis, risk stratification and management of smouldering multiple myeloma. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01119-0  January 22, 2026

Overview

Smoldering multiple myeloma is an early, symptom-free stage that always comes before active multiple myeloma. While treatments for multiple myeloma have greatly improved survival, the start of active disease is often linked to serious and permanent health problems. The course of smoldering multiple myeloma can vary widely. Some people have a slow-moving form that may never cause symptoms, while others have a higher-risk form that can progress to active disease quickly. In fact, nearly half of patients with high-risk smoldering multiple myeloma develop active multiple myeloma within two years of diagnosis.

Because of this risk, doctors closely monitor patients with smoldering multiple myeloma using blood tests and advanced imaging such as MRI or PET–CT scans to be sure active disease has not already started. Current tools help estimate a patient’s risk, but they are not perfect, and better methods are still needed. For patients with high-risk smoldering multiple myeloma, there is no single best approach. Some may benefit from starting treatment early to delay or prevent progression, while others may choose careful observation without treatment. The best plan depends on each patient’s risk level, overall health, and personal preferences, and should be decided through clear discussions between patients and their care team.

"T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What’s the Current Status?"

Source

Segers, F., Delforge, M. Antibody-Drug Conjugates, T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What’s the Current Status?. Targ Oncol (2026). https://doi.org/10.1007/s11523-025-01189-7  January 21, 2026. 

Overview

Treatment for multiple myeloma has changed a great deal over the past ten years. New immune-based therapies are now available that help the body’s own immune system find and attack cancer cells. These include antibody-drug conjugates, which deliver cancer-fighting medicine directly to myeloma cells, and T-cell therapies that train immune cells to recognize and destroy the cancer. Large clinical trials have shown strong results with these approaches, leading to approval by health authorities in Europe and the United States.

Several of these new treatments target a protein called B-cell maturation antigen, which is found on myeloma cells. Approved options include belantamab mafodotin, bispecific antibodies such as teclistamab, elranatamab, and linvoseltamab, and CAR T-cell therapies like idecabtagene vicleucel and ciltacabtagene autoleucel. Another approved therapy, talquetamab, targets a different protein found on myeloma cells. As more patients gain access to these treatments, it is important for doctors and patients to understand how well they work, what side effects they may cause, and why some patients stop responding over time. This review brings together results from major clinical trials, real-world patient experiences, and new research on treatment resistance to help guide future care for people with multiple myeloma.

"Anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy bb21217 for relapsed and refractory multiple myeloma: results from the phase 1 CRB-402 study"

Source

Melissa Alsina, Nina Shah, Sundar Jagannath, Jonathan L. Kaufman, David Siegel, Nikhil C. Munshi, Jacalyn Rosenblatt, Yi Lin, Andrzej J. Jakubowiak, Benjamin A. Derman, Aojun Li, Pingping Mao, Maeva Fincker, Ashish Yeri, Nathan Martin, Timothy B. Campbell, Olivia Finney, Anna Truppel-Hartmann, Fabio Petrocca, Jesus G. Berdeja, Noopur Raje; Anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy bb21217 for relapsed and refractory multiple myeloma: results from the phase 1 CRB-402 study. Cancer Immunol Res 2026; https://doi.org/10.1158/2326-6066.CIR-24-0527  January 21, 2026. 

Overview

Treatment for multiple myeloma has changed a great deal over the past ten years. New immune-based therapies are now available that help the body’s own immune system find and attack cancer cells. These include antibody-drug conjugates, which deliver cancer-fighting medicine directly to myeloma cells, and T-cell therapies that train immune cells to recognize and destroy the cancer. Large clinical trials have shown strong results with these approaches, leading to approval by health authorities in Europe and the United States.

Several of these new treatments target a protein called B-cell maturation antigen, which is found on myeloma cells. Approved options include belantamab mafodotin, bispecific antibodies such as teclistamab, elranatamab, and linvoseltamab, and CAR T-cell therapies like idecabtagene vicleucel and ciltacabtagene autoleucel. Another approved therapy, talquetamab, targets a different protein found on myeloma cells. As more patients gain access to these treatments, it is important for doctors and patients to understand how well they work, what side effects they may cause, and why some patients stop responding over time. This review brings together results from major clinical trials, real-world patient experiences, and new research on treatment resistance to help guide future care for people with multiple myeloma.

"Solute Carrier Family 19 Member 1 Mediates Acquired Bortezomib Resistance in Multiple Myeloma Through Chronic Stimulator of Interferon Genes Activation and Mitochondrial DNA Release"

Source

Chen, Y., X. Wu, M. Tang, X. Li, and X. Wang. 2026. “Solute Carrier Family 19 Member 1 Mediates Acquired Bortezomib Resistance in Multiple Myeloma Through Chronic Stimulator of Interferon Genes Activation and Mitochondrial DNA Release.” Cell Biology International 50: 1–15. https://doi.org/10.1002/cbin.70130. January 20, 2026. 

Overview

Acquired drug resistance is a major reason why some people with multiple myeloma do not respond well to treatment. Bortezomib is a common first-line therapy that is usually very effective, but many patients develop resistance over time. This study looked at a protein called SLC19A1, which is involved in how cells respond to low oxygen and regulate the immune system. Researchers found that SLC19A1 levels were higher in patients who had become resistant to bortezomib. In laboratory studies, increasing SLC19A1 made myeloma cells grow and spread more aggressively, but it did not cause resistance to bortezomib right away.

When cells were exposed to bortezomib over time, high SLC19A1 levels triggered a chain reaction involving another pathway called STING. This led to stress in the cell’s protein-handling system, disrupted the connection between the cell’s energy center and its protein factory, and caused mitochondrial DNA to leak. Blocking SLC19A1 with sulfasalazine or STING with an inhibitor called H-151 reduced this DNA release and made the cells sensitive to bortezomib again. These findings suggest that targeting SLC19A1 or STING could be a way to overcome drug resistance and improve treatment outcomes for patients with multiple myeloma.

"Independent prognostic factors predicting survival in multiple myeloma patients post-chemotherapy: a retrospective study"

Source

Luo, Y., Jiang, T., & Liu, L. (2026). Independent prognostic factors predicting survival in multiple myeloma patients post-chemotherapy: a retrospective study. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2613508  January 20, 2026. 

Overview

This study looked at simple ways to predict outcomes in people with multiple myeloma after chemotherapy. Researchers reviewed records from 164 patients who received standard treatments, including proteasome inhibitors or immunomodulatory drugs, between 2018 and 2024. They collected basic information such as age, blood counts, kidney function, calcium levels, and a protein called β2-microglobulin. They also looked at how well patients responded to four cycles of treatment and tracked how long patients lived and how long they remained free of disease progression.

After treatment, just over half of the patients achieved a very good or complete response, while the rest had a partial response or less. During follow-up, many patients experienced disease progression or death. Analysis showed that being over 60, having severe anemia, having high β2-microglobulin levels, and having a suboptimal response to initial treatment were linked to shorter overall survival. Low hemoglobin and a poor early response also predicted shorter progression-free survival. While these factors alone do not perfectly predict outcomes, they are simple, readily available measures that can help identify higher-risk patients, especially in settings where advanced tests like genetic profiling or minimal residual disease testing are not available. These factors could be combined in the future to create more accurate prognostic tools.

"Multiple Myeloma Derived Sulfur Dioxide Drives CAR-T Cell Exhaustion By Inducing Mitochondrial Dysfunction"

Source

Zhengyu Yu, Hua Lin, Jingran He, Linfeng Li, Zhongwang Wang, Kun Li, Ting Niu, Binquan Qiu, Multiple Myeloma Derived Sulfur Dioxide Drives CAR-T Cell Exhaustion By Inducing Mitochondrial Dysfunction, Redox Biology, 2026, 104040, ISSN 2213-2317, https://doi.org/10.1016/j.redox.2026.104040. January 19, 2026. 

Overview

This study looked at why CAR-T cell therapy, a powerful immune-based treatment for multiple myeloma, can sometimes stop working over time. Researchers found that sulfur dioxide (SO2), naturally produced in the body and present at higher levels in the bone marrow of patients with relapsed myeloma, can make CAR-T cells exhausted. High SO2 levels prevented CAR-T cells and other immune cells from entering the tumor area and caused changes in their gene activity that reduced their ability to fight cancer. SO2 also damaged the mitochondria—the energy centers of the cells—disrupting their function and reducing the CAR-T cells’ ability to produce important signaling molecules and kill cancer cells.

The study showed that SO2 acted through a specific protein called DRP1, which controls mitochondrial shape. SO2 caused chemical changes to DRP1 that led to abnormal mitochondrial splitting and loss of mitochondrial integrity. By altering a key site on DRP1, researchers were able to prevent these changes, restore normal mitochondrial function, and improve the CAR-T cells’ cancer-fighting ability. These findings reveal a new way that metabolism can interfere with CAR-T therapy and suggest that targeting the SO2–DRP1 pathway could help overcome this exhaustion and make CAR-T treatments more effective.

"Genomic mechanisms of resistance to venetoclax in multiple myeloma with t(11;14)(CCND1;IGH)"

Source

Marcella Kaddoura, Julia Erin Wiedmeier-Nutor, Vikas A Gupta, Tomas Jelinek, Bachisio Ziccheddu, Suganti Shivaram, Hongwei Tang, Rebecca W Owens, Tereza Ševčíková, Rodrigo Fonseca, Michael A. Durante, Benjamin T. Diamond, Logan Zhao, Yuan Xiao Zhu, Chang-Xin Shi, Shannon M Matulis, Constantine S. Mitsiades, Carl Ola Landgren, Saad Z. Usmani, Roman Hajek, Marta Chesi, P. Leif Bergsagel, Esteban Braggio, Lawrence H Boise, Rafael Fonseca, Shaji K Kumar, Francesco Maura, Linda B Baughn; Genomic mechanisms of resistance to venetoclax in multiple myeloma with t(11;14)(CCND1;IGH). Blood 2026; blood.2025029996. doi: https://doi.org/10.1182/blood.2025029996  January 2, 2026. 

Overview

Some people with multiple myeloma have a specific genetic change called t(11;14), which makes their cancer more likely to respond to a targeted drug called venetoclax. However, not all patients with this genetic change benefit from treatment, and some see their disease worsen soon after an initial response. This study looked at why that happens by analyzing the genetic makeup of myeloma cells from patients treated with venetoclax.

The researchers found that mutations in the RAS pathway, which helps control cell growth, were strongly linked to shorter periods of disease control. Patients with these mutations were more likely to stop responding to venetoclax sooner. In patients without RAS mutations, another genetic change called 1q gain was also linked to poorer outcomes. When the disease progressed after treatment, the myeloma cells often showed new or expanding genetic changes that helped them survive, including changes affecting cell survival pathways and other high-risk features.

Overall, the study shows that detailed genetic testing can help explain why venetoclax stops working in some patients with t(11;14) multiple myeloma. Understanding these genetic changes may help doctors better predict who is most likely to benefit from venetoclax and guide more personalized treatment decisions in the future.

"Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort"

Source

Martin TG, Mateos M-V, Yi JH, et al. Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort. Cancer. 2026;e70237. doi:10.1002/cncr.70237  January 4, 2026.  

Overview

This study looked at how well teclistamab works and how safe it is for people with relapsed or refractory multiple myeloma who have already been treated with all three main drug classes. Teclistamab is a bispecific antibody that helps the immune system recognize and attack myeloma cells by targeting a protein called B-cell maturation antigen. Researchers reviewed results from several clinical trials and from patients who received the drug through an early access program, including groups from Asia and other parts of the world.

Across all studies, many patients had advanced disease and had already received several prior treatments. Despite this, about two thirds of patients responded to teclistamab, and many achieved a deep response, including complete remission. In Asian patients, response rates were similar or even higher, and many patients remained free from disease progression for two years or longer. Side effects were generally manageable and most often included low blood counts, immune-related reactions, and infections. Over time, better infection prevention and treatment improved safety outcomes. Overall, these findings show that teclistamab provides meaningful and lasting benefits for a wide range of patients and supports its role as an important treatment option for people with difficult-to-treat multiple myeloma.

"Pharmacovigilance study on neurological adverse reactions of proteasome inhibitors in the FDA adverse event reporting system"

Source

Li S, Ling T, Liu Y, Li J. Pharmacovigilance study on neurological adverse reactions of proteasome inhibitors in the FDA adverse event reporting system. Front Pharmacol. 2026 Jan 5;16:1712361. doi: 10.3389/fphar.2025.1712361.  

Overview

This study looked at nerve-related side effects linked to three common drugs used to treat multiple myeloma: bortezomib, carfilzomib, and ixazomib. These medicines belong to a group called proteasome inhibitors and are widely used, but they can affect the nervous system. Researchers reviewed reports from a large U.S. safety database that collects information on side effects reported in real-world use over more than 20 years. They examined both peripheral nerve problems, such as numbness or tingling in the hands and feet, and less common effects involving the brain and central nervous system.

The analysis showed that nerve damage in the hands and feet was the most common problem for all three drugs, especially bortezomib, which had the highest number and strongest signals of nerve-related side effects. Bortezomib was most strongly linked to problems affecting automatic body functions, while carfilzomib showed a higher link to serious brain-related conditions associated with high blood pressure. Ixazomib had fewer nerve-related reports overall, but was linked to specific symptoms such as burning pain in the feet and nerve pain related to shingles. Nerve symptoms usually appeared within the first one to three months of treatment. Overall, the findings suggest that carfilzomib and ixazomib may cause less nerve damage than bortezomib, but all three drugs require careful monitoring so that nerve problems can be recognized and treated early.

"Bispecific Antibodies: Strategies Available to Optimize Their Safe Delivery in Patients with Multiple Myeloma. Antibodies"

Source

Giles, H. V., & Kishore, B. (2026). Bispecific Antibodies: Strategies Available to Optimize Their Safe Delivery in Patients with Multiple Myeloma. Antibodies, 15(1), 5. https://doi.org/10.3390/antib15010005  January 5, 2026.  

Overview

Bispecific antibodies are a newer type of treatment for multiple myeloma that have become available in recent years. They work by helping the immune system’s T cells find and attack myeloma cells. At present, these drugs are approved mainly for people whose myeloma has come back or stopped responding after at least three different types of treatment. Studies are now testing whether bispecific antibodies can be used earlier in the disease, and early results are encouraging. These treatments have unique side effects, most commonly a flu-like reaction called cytokine release syndrome, which is usually mild and happens when treatment is first started. Less often, they can cause temporary nerve-related symptoms. Because these effects usually occur early, many patients are hospitalized during the first doses, although newer approaches may allow more people to be treated safely as outpatients.

One of the biggest challenges with bispecific antibodies is infection risk. These treatments weaken parts of the immune system, making infections the leading non-cancer cause of death in patients receiving them. Doctors use several strategies to lower this risk, including adjusting how often the drug is given once a patient is responding, giving immune globulin replacements when antibody levels drop, and closely managing low white blood cell counts. Preventive antiviral medicines are routinely used, and patients are screened and protected against hepatitis B when needed. Vaccinations with non-live vaccines are recommended, ideally before treatment starts, although responses to vaccines are often weaker during therapy. Antibiotics and antifungal medicines may be used in selected patients based on individual risk. Overall, bispecific antibodies are an important advance in multiple myeloma care, but careful monitoring and supportive care are essential to keep patients safe and allow them to benefit fully from these powerful treatments.

"Infection risks associated with daratumumab-containing regimens in multiple myeloma: a systematic review and meta-analysis"

Source

Huang ZY, Liu XL, Li T, Luo CH. Infection risks associated with daratumumab-containing regimens in multiple myeloma: a systematic review and meta-analysis. Front Oncol. 2026 Jan 6;15:1729177. doi: 10.3389/fonc.2025.1729177. 

Overview

Daratumumab is a widely used treatment for multiple myeloma and is given to patients both at diagnosis and after the disease has returned. It works by targeting a protein called CD38 on myeloma cells, but it can also affect normal immune cells and lower antibody levels. Because of this, there has been concern that daratumumab may raise the risk of infections. To better understand this risk, researchers reviewed results from several large clinical trials that compared daratumumab-based treatments with standard therapies.

The review included nine studies with more than 5,000 patients. Overall, patients who received daratumumab were more likely to develop infections, including serious infections and pneumonia. Severe infections were more common, but deaths caused by infection were rare and occurred at similar rates whether or not patients received daratumumab. These findings were consistent across different patient groups, including those treated early in their disease and those who had relapsed. While daratumumab remains an important and effective therapy, the results highlight the need for careful monitoring and early prevention of infections as its use continues to grow

"Efficacy, safety and economy of denosumab and zoledronic acid in the treatment of bone metastases of solid tumors and multiple myeloma: a systematic review and meta-analysis"

Source

Zhong L, Chen W, Zheng D, Cao Y, Zhu L, Zhu Z, Liao L, Dai L, Wang X, Zeng Z. Efficacy, safety and economy of denosumab and zoledronic acid in the treatment of bone metastases of solid tumors and multiple myeloma: a systematic review and meta-analysis. Front Oncol. 2026 Jan 6;15:1747354. doi: 10.3389/fonc.2025.1747354. 

Overview

This study compared two common bone-protecting treatments, denosumab and zoledronic acid, in people with cancer that has spread to the bones, including those with multiple myeloma. These drugs are used to prevent serious bone problems such as fractures, spinal cord compression, and the need for surgery or radiation to the bones. Researchers reviewed results from more than 20 studies, including clinical trials and cost analyses, to better understand how well each drug works, how safe they are, and how affordable they may be in different healthcare settings.

Overall, denosumab helped delay bone-related complications compared with zoledronic acid, especially in patients with solid tumors. However, this benefit was not clearly seen in patients with multiple myeloma. Both drugs showed similar effects on overall survival and disease control. Denosumab was linked to fewer side effects overall and was less likely to cause kidney problems. When cost was considered, denosumab was more likely to be cost-effective in wealthier countries, while zoledronic acid was usually the more affordable option in regions with fewer resources. These findings suggest that treatment choice should take into account the type of cancer, potential side effects, and local healthcare costs.

"The addition of CD38 monoclonal antibody to triplet regimens improves survival in newly diagnosed multiple myeloma with high-risk cytogenetics: a systematic review and meta-analysis of randomized controlled trials"

Source

Hu B, Fang D, Jiang L, Li T, Chen K, Cao J, Wang J. The addition of CD38 monoclonal antibody to triplet regimens improves survival in newly diagnosed multiple myeloma with high-risk cytogenetics: a systematic review and meta-analysis of randomized controlled trials. Front Immunol. 2026 Jan 6;16:1744165. doi: 10.3389/fimmu.2025.1744165

Overview

This study looked at whether adding a CD38-targeting antibody to standard treatment improves outcomes for people newly diagnosed with multiple myeloma who have high-risk genetic features. These patients often have a more aggressive form of the disease and may not respond as well to treatment. Researchers combined results from nine clinical trials involving more than 4,500 patients to compare four-drug treatment plans with standard three-drug regimens.

The analysis showed that four-drug regimens that included a CD38 antibody led to deeper treatment responses, meaning more patients had no detectable cancer after treatment. These regimens also helped patients stay free from disease progression for a longer time. The benefit was strongest with daratumumab-based treatments. However, not all patients saw the same advantage. Patients who were not eligible for stem cell transplant and those treated with isatuximab-based regimens did not show a clear improvement in progression-free survival. Overall, the findings support the use of daratumumab-containing four-drug regimens to improve outcomes in newly diagnosed patients with high-risk multiple myeloma.

"Multiple myeloma risk linked to DNA damage response genes"

Source

Conry, M., Ostrovnaya, I., Kemel, Y. et al. Multiple myeloma risk linked to DNA damage response genes. J Hematol Oncol (2026). https://doi.org/10.1186/s13045-025-01776-1  January 6, 2026. 

Overview

This study looked at whether inherited changes in certain genes involved in DNA repair increase the risk of developing multiple myeloma. While these genes are known to play a role in other cancers, their impact on multiple myeloma has not been well studied. Researchers compared genetic data from more than 3,400 people with multiple myeloma to data from over 323,000 people without cancer.

They found that rare inherited mutations in several genes, including TP53, ATM, CHEK2, KDM1A, and ARID1A, were linked to a higher risk of developing multiple myeloma. These genetic changes were more common in people who developed the disease at a younger age or who had a family history of multiple myeloma. Patients with inherited changes in TP53 or ATM also tended to have poorer survival outcomes. Overall, the findings suggest that these DNA repair genes may play a role in multiple myeloma risk and severity. Identifying people who carry these inherited mutations could help doctors monitor higher-risk individuals more closely, especially those with early-onset disease or a strong family history.

"Combination therapy of BCL-2 antagonist venetoclax and demethylase inhibitor azacitidine for the treatment of multiple myeloma: a clinical study"

Source

Wang, Y., Rao, B., Sun, S., & Zhu, H. (2026). Combination therapy of BCL-2 antagonist venetoclax and demethylase inhibitor azacitidine for the treatment of multiple myeloma: a clinical study. Leukemia & Lymphoma, 1–11. https://doi.org/10.1080/10428194.2025.2606209 January 7, 2026. 

Overview

This clinical trial studied a combination of two drugs, venetoclax and azacitidine, in people with multiple myeloma. The goal was to see how well the treatment worked and how safe it was. Researchers followed 440 patients and measured how many responded to treatment, how deeply the cancer responded, how long the disease stayed under control, and what side effects occurred. The combination showed meaningful activity, especially in patients with high-risk genetic features, where deeper responses were more common.

Side effects were generally manageable. About one quarter of patients developed low white blood cell counts, and fatigue was also common. Certain factors helped predict who benefited most from treatment, including having no detectable disease after therapy and specific genetic changes such as t(11;14). Overall, the results suggest that this drug combination may be helpful for selected patients with difficult-to-treat or high-risk multiple myeloma. However, longer follow-up and larger studies are still needed before this approach can be considered part of routine care.

"MRD Directed Consolidation in Multiple Myeloma – Are We There Yet?"

Source

Mirgh, Dr Sumeet et al. MRD Directed Consolidation in Multiple Myeloma – Are We There Yet? Clinical Lymphoma, Myeloma and Leukemia, Volume 0, Issue 0 January 7, 2026. 

Overview

Autologous stem cell transplant has been a standard part of treatment for newly diagnosed multiple myeloma for many years. Even in the modern era of effective three-drug regimens, large studies have shown that transplant continues to provide long-term benefit. More recently, very deep responses achieved with newer four-drug combinations and the ability to measure minimal residual disease (MRD) have raised questions about whether all patients still need a transplant, or whether treatment can be tailored based on response.

Recent studies suggest that the depth of response continues to improve with longer and more intensive induction therapy, regardless of whether three- or four-drug regimens are used. Extended induction can lead to high rates of MRD negativity even before transplant, which challenges the traditional timing of transplant after only a few treatment cycles. However, deeper early responses do not always translate into better long-term outcomes. Evidence from prior trials shows that sustained MRD negativity over time, rather than a single negative test, is more strongly linked to prolonged disease control, and transplant has consistently been associated with more durable remissions and longer progression-free survival.

The role of MRD-guided treatment decisions also appears to differ across patient subgroups. Certain genetic subtypes, such as those with t(11;14) disease or MGUS-like features, may have slower or less complete responses without compromising long-term survival, while other high-risk patients can relapse early despite achieving MRD negativity. These findings highlight the limitations of using MRD alone to decide whether to intensify or reduce therapy.

Cost and access are also critical considerations, particularly in low- and middle-income countries. Prolonged use of expensive four-drug regimens without transplant is often far less cost-effective than standard triplet therapy followed by transplant, while delivering inferior long-term value. Taken together, current evidence suggests that although MRD assessment is an important tool, it should not yet replace autologous transplant as consolidation therapy for most eligible patients. Longer follow-up and carefully designed studies are needed before MRD-guided strategies can safely redefine the role of transplant in multiple myeloma.

"Cost-utility of pre-emptive plerixafor versus rescue plerixafor in the mobilization of hematopoietic stem cells in multiple myeloma"

Source

Feldens, T., Mesquita Augusto Passos, R., de Oliveira Martins, J., Campolina, A. G., & de Almeida Neto, C. (2015). Cost-utility of pre-emptive plerixafor versus rescue plerixafor in the mobilization of hematopoietic stem cells in multiple myeloma. Expert Review of Pharmacoeconomics & Outcomes Research. https://doi.org/10.1080/14737167.2026.2612985  January 7, 2026. 

Overview

Multiple myeloma is a blood cancer that is becoming more common worldwide. For many patients, an autologous stem cell transplant is an important part of treatment. To make this possible, enough stem cells must be collected from the blood, but in some patients this process does not work well. Plerixafor is a drug that helps release stem cells into the bloodstream, but it is expensive and not always used in a consistent way.

This study looked at whether it is better to give plerixafor early to prevent problems or to use it only after standard stem cell collection has failed. Using real-world data from patients treated in Brazil, researchers found that giving plerixafor early led to more successful stem cell collections and more patients going on to transplant. Although this approach cost more upfront, it provided better overall value by improving quality of life and outcomes. Based on these results, using plerixafor early appears to be a cost-effective option in Brazil and may help guide healthcare decisions about how best to use limited resources.

"Iron Overload and Anemia in Transferrin Immune Complex Disease, an Overlooked Monoclonal Gammopathy of Clinical Significance"

Source

G. L. Forni, E. Stampone, V. M. Pinto, et al., “Iron Overload and Anemia in Transferrin Immune Complex Disease, an Overlooked Monoclonal Gammopathy of Clinical Significance,” American Journal of Hematology (2026): 1–6, https://doi.org/10.1002/ajh.70187.  January 7, 2026. 

Overview

Transferrin–Immune Complex Disease (TICD) is a rare and often overlooked condition linked to an abnormal protein in the blood. In this disease, the immune system produces antibodies that bind to transferrin, a protein that normally carries iron through the body. When these immune complexes form, they can cause unusually high levels of iron and transferrin in the blood. TICD is not harmless. People with this condition have a higher risk of iron overload (hemochromatosis), anemia, and progression to serious blood cancers such as multiple myeloma. Because only a small number of cases have been reported, the condition is likely underdiagnosed.

Research suggests that TICD disrupts the body’s normal iron regulation system, particularly hormones that control how iron is absorbed and stored. This disruption may explain why patients can have both iron overload and anemia at the same time, a combination that makes treatment challenging. The disease may be missed in many patients with monoclonal gammopathy because not all antibody–transferrin complexes cause obvious changes in blood iron tests. By actively screening patients who have high iron levels, high transferrin levels, and abnormal blood proteins, researchers were able to identify several previously unrecognized cases.

Experts now propose that TICD should be classified as a form of “monoclonal gammopathy of clinical significance,” meaning a condition where an abnormal antibody directly causes organ or tissue damage. It may also represent a newly recognized acquired form of hemochromatosis. For patients, this means that unexplained high iron levels together with abnormal blood proteins should prompt further testing for anti-transferrin antibodies. Early identification is important, as treatment decisions are complex and there is a risk of disease progression. Ongoing monitoring and additional blood tests may help identify those at highest risk and guide timely treatment.

"Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial"

Source

Hermann Einsele, Jesús San-Miguel, Binod Dhakal, Cyrille Touzeau, Xavier Leleu, Niels WCJ van de Donk, Surbhi Sidana, Albert Oriol, Yael C Cohen, Simon J Harrison, María-Victoria Mateos, Joaquín Martínez-López, Paolo Corradini, Lionel Karlin, Diana Chen, Quanlin Li, Tzu-min Yeh, Katherine Li, Vicki Plaks, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, Martin Vogel, Jordan M Schecter, Nikoletta Lendvai, Mythili Koneru, Nitin Patel, Erika Florendo, Phoebe Joy Ho, Rakesh Popat, Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial, The Lancet Oncology, 2026, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(25)00653-9.  January 7, 2026.  

Overview

This study looked at a newer treatment called ciltacabtagene autoleucel, or cilta-cel, for people with multiple myeloma whose disease no longer responds to lenalidomide, a commonly used drug. Cilta-cel is a type of CAR T-cell therapy, which uses a patient’s own immune cells to target and destroy cancer cells. In a large international clinical trial called CARTITUDE-4, patients who received a single infusion of cilta-cel lived longer without their disease getting worse and also showed improved overall survival compared with those who received standard drug treatments.

The trial included adults who had already received one to three prior treatments for multiple myeloma. After more than two and a half years of follow-up, many patients treated with cilta-cel were still alive and free from disease progression, while patients receiving standard therapy experienced relapse much sooner. Overall survival was significantly better in the cilta-cel group, meaning fewer patients died compared with those receiving usual care. Importantly, many patients treated with cilta-cel did not need further myeloma treatment for long periods after their infusion, suggesting deep and lasting disease control.

Side effects were common in both treatment groups, especially low blood counts, which can increase the risk of infection and fatigue. These effects were expected with CAR T-cell therapy and were generally manageable with medical care. Serious side effects occurred at similar rates in both groups, and deaths related to treatment were uncommon. Quality of life was also better maintained with cilta-cel, with patients reporting a slower worsening of myeloma-related symptoms compared with standard treatments.

Overall, this study provides strong evidence that a one-time cilta-cel infusion can offer meaningful survival and quality-of-life benefits for patients with relapsed or refractory multiple myeloma, even as early as the first relapse. These results support the growing role of CAR T-cell therapy as an effective treatment option earlier in the course of myeloma care.

"Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study"

Source

Bar, N., Martin, T., Hofmeister, C.C. et al. Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study. Leukemia (2026). https://doi.org/10.1038/s41375-025-02841-x  January 7, 2026.   

Overview

This study looked at a newer type of immune-based treatment for multiple myeloma called alnuctamab. Alnuctamab is a bispecific antibody, which means it is designed to connect two types of cells at the same time. One part attaches to myeloma cells, and the other part activates T cells, a key part of the immune system, to help attack the cancer. The study focused on people with relapsed or refractory multiple myeloma whose disease had returned or stopped responding after at least three previous treatments.

Patients in this early-phase clinical trial received alnuctamab either through a vein or as an injection under the skin. The under-the-skin method was chosen for further study because it caused fewer serious side effects. Nearly 100 patients received this form of treatment, and many were still benefiting from therapy at the time of analysis. More than half of the patients responded to treatment, and response rates were even higher at the recommended dose. Almost half of the patients had no measurable signs of myeloma left using very sensitive testing, showing that the treatment could lead to deep responses.

Side effects were common but generally manageable. The most frequent reaction was cytokine release syndrome, a flu-like immune response that occurred mostly at mild levels. Low white blood cell counts and infections were also seen, which is expected with immune-based treatments and requires close monitoring. Importantly, adjusting the dose gradually at the start of treatment helped reduce side effects, and spacing out doses over time appeared to improve tolerability.

Overall, alnuctamab showed promising effectiveness and a safety profile similar to other BCMA-targeting treatments already used in multiple myeloma. Giving the drug as an injection under the skin and slowly increasing the dose helped lower the risk of serious side effects. These results suggest that alnuctamab may become another useful option for patients with advanced multiple myeloma and may help guide safer use of similar immune therapies in the future.

"Temporal trends in progression risk in smoldering myeloma: a systematic review"

Source

Ludwig H, Kastritis E, Bernhard S, van de Donk NWCJ, Boccadoro M, Terpos E, Musto P, Sonneveld P, Mohyuddin GR. Temporal trends in progression risk in smoldering myeloma: a systematic review. EClinicalMedicine. 2026 Jan 8;91:103750. doi: 10.1016/j.eclinm.2025.103750.   

Overview

Smoldering multiple myeloma is an early, symptom-free form of myeloma that does not always progress to active cancer. This large review looked at how the outlook for people with smoldering myeloma has changed over the past several decades. By analyzing results from many studies published between 1990 and 2025, the researchers found that people diagnosed more recently tend to progress more slowly to active myeloma than those diagnosed years ago. This suggests that smoldering myeloma today is often a more slow-moving condition than it once appeared to be.

One major reason for this change is better testing and clearer diagnostic rules. In the past, some people with early but already active myeloma were mistakenly labeled as having smoldering myeloma because imaging tools were less sensitive and blood tests were less precise. Since 2014, updated international guidelines and improved imaging scans have helped doctors more accurately separate true smoldering myeloma from active disease. As a result, people now diagnosed with smoldering myeloma are more likely to truly have a lower-risk condition.

The study also showed that the risk of progression is highest in the first few years after diagnosis and then decreases over time, especially for people who remain stable for five years or longer. Even among patients considered “high risk,” progression now tends to happen later than it did in older studies. This means that many patients, including some previously labeled high risk, may live for many years without needing treatment.

These findings are important because many current risk models were created using older patient data and may overestimate today’s risk of progression. Treating smoldering myeloma too early can expose patients to unnecessary side effects, costs, and stress. The authors emphasize that modern care should focus on careful monitoring and more personalized risk assessment, using updated tests and trends over time rather than relying only on older models.

Overall, this research shows that smoldering multiple myeloma has become a more clearly defined and often less aggressive condition. Better diagnosis allows doctors to identify who truly needs early treatment and who can safely be observed. This approach helps patients avoid unnecessary therapy while ensuring that those at highest risk receive timely care, improving both quality of life and long-term outcomes.

"The efficacy and safety of CAR-T therapy in relapsed or refractory multiple myeloma patients: a systematic review and meta-analysis"

Source

Zhou, Y., Xie, X., Feng, K., Cao, W., & Zhang, D. (2026). The efficacy and safety of CAR-T therapy in relapsed or refractory multiple myeloma patients: a systematic review and meta-analysis. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2613505 January 8, 2026. .   

Overview

CAR-T cell therapy is a new and powerful treatment option for people with multiple myeloma that has returned after previous treatment or that does not respond to standard therapy. This review looked at 29 studies published between 2021 and 2024, including nearly 1,400 patients, to understand how well CAR-T therapy works and how safe it is. The results show that CAR-T therapy is highly effective, with about 86% of patients responding to treatment and 78% achieving no detectable disease using sensitive tests. On average, patients went nearly 10 months without their disease getting worse, and responses lasted about 12 months.

While CAR-T therapy works well, it can cause side effects that need careful monitoring. Most patients (83%) experience some level of cytokine release syndrome (CRS), which is a reaction that can cause fever and flu-like symptoms, but only 5% develop severe CRS. Serious nervous system side effects are rare, occurring in just 2% of patients, and infections are common but can be managed with preventive strategies and supportive care. Blood cell counts may drop temporarily, but these usually recover over time with medical support.

CAR-T therapy is also being tested earlier in the course of multiple myeloma. In newly diagnosed patients, it has shown even higher response rates with fewer side effects, suggesting it could become an important option earlier in treatment. However, challenges remain, including the complexity of producing CAR-T cells, high costs, long wait times, and the potential for the therapy to lose effectiveness over time. Researchers are developing “off-the-shelf” CAR-T products and exploring new targets to make treatment more accessible and durable.

Overall, this evidence shows that CAR-T therapy offers a major advance for patients with relapsed or refractory multiple myeloma, providing high response rates and generally manageable side effects. Ongoing research and clinical trials are working to improve safety, access, and long-term effectiveness, offering hope that CAR-T therapy could transform the way multiple myeloma is treated in the future.

"Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study"

Source

Beksac, M., Fıratlı Tuglular, T., Gay, F., Mina, R., Katodritou, E., Unal, A., Cavo, M., Ozsan, G.H., van der Velden, V.H.J., Beverloo, B.H., Vermeulen, M., van Duin, M., Seval, G.C., Sevindik, O.G., Merante, S., Manousou, K., Sonneveld, P., Zamagni, E. and Terpos, E. (2026), Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study. HemaSphere, 10: e70287. https://doi.org/10.1002/hem3.70287  January 8, 2026.   

Overview

The EMN19 study explored a new treatment approach for patients with multiple myeloma who also have extramedullary plasmacytomas, which are tumors outside the bone marrow. This Phase II trial treated 40 patients—29 with newly diagnosed myeloma and 11 at first relapse—with a combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone, known as DaraVCD, given for up to three years or until the disease progressed. The main goal was to achieve a complete blood response. After about 30 months of follow-up, nearly half of the patients (47.5%) reached this response, and most of those also had no detectable disease by sensitive lab tests and imaging. Patients who reached these deep responses had much longer periods without disease progression compared with others.

The study also looked at circulating tumor cells, which were found at very low levels in this group, marking the first prospective report of these cells in patients with extramedullary disease. Patients with newly diagnosed myeloma generally had higher response rates than those with relapsed disease, likely because they were healthier and had less advanced disease. DaraVCD was well tolerated over the long treatment period, with the most common side effects being low blood counts and infections. Serious side effects were seen in about one-third of patients, but only one patient had to stop treatment because of side effects.

Overall, EMN19 shows that DaraVCD can produce strong and rapid responses in patients with myeloma and extramedullary plasmacytomas, especially in newly diagnosed patients, and it can be used safely over an extended period. However, these patients still face higher risks compared with the broader myeloma population, highlighting the need for additional strategies, including newer immunotherapies, to further improve outcomes in this high-risk group..

"Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study"

Source

Beksac, M., Fıratlı Tuglular, T., Gay, F., Mina, R., Katodritou, E., Unal, A., Cavo, M., Ozsan, G.H., van der Velden, V.H.J., Beverloo, B.H., Vermeulen, M., van Duin, M., Seval, G.C., Sevindik, O.G., Merante, S., Manousou, K., Sonneveld, P., Zamagni, E. and Terpos, E. (2026), Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study. HemaSphere, 10: e70287. https://doi.org/10.1002/hem3.70287  January 8, 2026.   

Overview

The EMN19 study explored a new treatment approach for patients with multiple myeloma who also have extramedullary plasmacytomas, which are tumors outside the bone marrow. This Phase II trial treated 40 patients—29 with newly diagnosed myeloma and 11 at first relapse—with a combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone, known as DaraVCD, given for up to three years or until the disease progressed. The main goal was to achieve a complete blood response. After about 30 months of follow-up, nearly half of the patients (47.5%) reached this response, and most of those also had no detectable disease by sensitive lab tests and imaging. Patients who reached these deep responses had much longer periods without disease progression compared with others.

The study also looked at circulating tumor cells, which were found at very low levels in this group, marking the first prospective report of these cells in patients with extramedullary disease. Patients with newly diagnosed myeloma generally had higher response rates than those with relapsed disease, likely because they were healthier and had less advanced disease. DaraVCD was well tolerated over the long treatment period, with the most common side effects being low blood counts and infections. Serious side effects were seen in about one-third of patients, but only one patient had to stop treatment because of side effects.

Overall, EMN19 shows that DaraVCD can produce strong and rapid responses in patients with myeloma and extramedullary plasmacytomas, especially in newly diagnosed patients, and it can be used safely over an extended period. However, these patients still face higher risks compared with the broader myeloma population, highlighting the need for additional strategies, including newer immunotherapies, to further improve outcomes in this high-risk group..

"Comparison of Second Revision of the International Staging System (R2-ISS) and Mayo Additive Staging System (MASS) in Newly Diagnosed Multiple Myeloma Patients"

Source

Baysal, M., Demirci, U., Bulut, E. et al. Comparison of Second Revision of the International Staging System (R2-ISS) and Mayo Additive Staging System (MASS) in Newly Diagnosed Multiple Myeloma Patients. Indian J Hematol Blood Transfus (2026). https://doi.org/10.1007/s12288-025-02305-3  January 8, 2026.    

Overview

A recent study compared two newer systems for classifying risk in patients with newly diagnosed multiple myeloma: the Revised International Staging System (R2-ISS) and the Mayo Additive Staging System (MASS). Researchers analyzed 220 patients and looked at how well each system predicted overall survival. Using R2-ISS, median survival ranged from 85.5 months for low-risk patients to just 13 months for high-risk patients. MASS showed similar trends, with median survival of 66 months for the lowest risk group and 24 months for the highest. The study also found a strong positive correlation between the two systems, indicating that they generally classify patients in similar ways. Overall, both R2-ISS and MASS were effective for identifying patients with different levels of risk and are practical tools that can be used in routine clinical care to guide treatment decisions.

"Is Less 'Sufficient' and 'Safe' in the MRD Era - Outcomes of Autologous Stem-Cell Transplant as per Melphalan Dose in Patients with Multiple Myeloma"

Source

Mirgh, S., Goel, A., Punatar, S. et al. Is Less “Sufficient” and “Safe” in the MRD Era - Outcomes of Autologous Stem-Cell Transplant as per Melphalan Dose in Patients with Multiple Myeloma. Blood Cancer J. 16, 10 (2026). https://doi.org/10.1038/s41408-025-01437-z  January 8, 2026.  

Overview

This study looked back at the records of people with multiple myeloma in India who had a stem cell transplant over a 15-year period. The goal was to see whether a lower dose of the chemotherapy drug melphalan worked as well as the standard higher dose when used before transplant. Doctors compared people who received the full dose with those who received a reduced dose, usually because of kidney problems or other health concerns.

In total, 176 patients were included in the final analysis. Before transplant, all patients went through detailed testing to check organ function, infections, and overall health. Imaging scans and bone marrow tests were also used to see how much disease remained. Some patients had no detectable cancer cells by very sensitive testing, while others still had signs of disease. These results helped doctors understand who might benefit from different treatment doses.

The researchers followed patients after transplant to see how long the disease stayed under control and how long patients lived. They also looked at results in specific groups, such as patients whose disease was already responding well before transplant, those with standard-risk versus high-risk genetic features, and those with positive or negative scan and bone marrow results.

Overall, the lower dose of melphalan worked about as well as the higher dose for many patients. People with standard-risk disease and no detectable cancer cells before transplant had similar outcomes regardless of dose. However, patients with high-risk genetic features or clear signs of remaining disease before transplant tended to do better with the higher dose. The study also found that the higher dose caused more severe mouth sores and other short-term side effects, which can affect recovery and quality of life.

The authors note that patients in this study were younger and often had stronger responses to treatment before transplant than patients in older studies, likely because newer drug combinations were used. This may explain why many patients did well even with a lower melphalan dose. The study has limits, including changes in treatment approaches over time and the lack of some newer therapies.

In summary, a reduced dose of melphalan before stem cell transplant may be a safe and effective option for many people with multiple myeloma, especially those with standard-risk disease and no detectable cancer before transplant. More future studies are needed to confirm whether test results like minimal residual disease can help doctors personalize the melphalan dose for each patient.

"Hypoxia promotes BCMA loss and a suppressive secretome thereby hindering CAR T cell therapy in multiple myeloma"

Source

Tu, C., Van der Vreken, A., Meeus, F. et al. Hypoxia promotes BCMA loss and a suppressive secretome thereby hindering CAR T cell therapy in multiple myeloma. Exp Hematol Oncol 15, 1 (2026). https://doi.org/10.1186/s40164-025-00732-6  January 8, 2026. 

Overview

This study looked at how low oxygen levels in the bone marrow affect multiple myeloma cells and their response to a type of immunotherapy called BCMA CAR T cell therapy. In the body, myeloma grows in the bone marrow, which often has less oxygen than normal tissues. Low oxygen, also called hypoxia, is known to weaken immune responses, but its effects on treatment targets like BCMA have not been fully understood.

Researchers grew myeloma cells in normal oxygen levels and in very low oxygen levels to mimic the bone marrow environment. They then measured how much BCMA was present on the surface of the cancer cells and inside the cells. They also tested how well BCMA-targeted CAR T cells could kill the cancer cells and release immune signaling proteins.

Myeloma cells grown in low oxygen had much lower levels of BCMA. Because of this, CAR T cells were less able to recognize and attack them. The researchers also found that myeloma cells in low oxygen released substances into their surroundings that further reduced BCMA levels and made CAR T cells less effective. As a result, CAR T cells killed fewer cancer cells and produced fewer immune signals.

A closer look showed that low-oxygen myeloma cells released higher amounts of very small particles called extracellular vesicles. These particles carried RNA linked to immune suppression and appeared to play a role in weakening CAR T cell activity. Blocking an enzyme involved in BCMA shedding partly restored BCMA levels and improved CAR T cell function, suggesting this effect may be reversible.

In summary, low oxygen levels in the bone marrow can make myeloma cells harder for CAR T cells to target by lowering BCMA and releasing immune-suppressing signals. Although these findings come from laboratory experiments, they likely reflect what happens inside the body. Future studies in patients will be needed to see whether addressing low oxygen or BCMA shedding can improve the success of CAR T cell therapy in multiple myeloma.

"Knockdown of caspase-activated DNase and B-cell lymphoma 2 inhibits cell proliferation and drug resistance in TP53-mutant multiple myeloma"

Source

Tian, F., Wang, J., Zhang, P. et al. Knockdown of caspase-activated DNase and B-cell lymphoma 2 inhibits cell proliferation and drug resistance in TP53-mutant multiple myeloma. Inflamm. Res. 75, 16 (2026). https://doi.org/10.1007/s00011-025-02151-z  January 8, 2026. 

Overview

This study focused on a small group of multiple myeloma cases that carry changes in a gene called TP53. Although TP53 mutations are not common in myeloma, they are linked to more aggressive disease and resistance to treatment. The researchers wanted to understand how two proteins, called CAD and BCL-2, help TP53-mutant myeloma cells grow and survive cancer drugs.

In laboratory experiments, the team compared myeloma cells with normal TP53 to cells with TP53 mutations. The TP53-mutant cells had higher levels of CAD and BCL-2. Researchers then used genetic tools to lower, or “turn down,” CAD and BCL-2 in the TP53-mutant cells and studied how this affected cell growth, survival, and response to treatment.

When CAD or BCL-2 levels were reduced, the cancer cells grew more slowly and were more likely to undergo programmed cell death. These cells also became stuck at a checkpoint in the cell cycle, which prevented them from dividing normally. At the same time, proteins linked to drug resistance decreased, making the cells more sensitive to common myeloma drugs such as bortezomib and doxorubicin.

The strongest effects were seen when both CAD and BCL-2 were reduced together. This combination further blocked cell division, increased cancer cell death, and lowered resistance to treatment. In animal studies, tumors made from TP53-mutant myeloma cells grew more slowly when both proteins were suppressed and responded better to bortezomib.

In summary, this research suggests that CAD and BCL-2 play an important role in helping TP53-mutant myeloma cells survive and resist treatment. Targeting both proteins at the same time may be a promising approach to improve treatment responses in this hard-to-treat form of multiple myeloma, although more research in patients is still needed.

"The effect of semi-automatic segmentation approaches on semi-quantitative parameters of 68Ga-Pentixafor PET-CT in newly diagnosed multiple myeloma patients"

Source

Tang, R., Wan, Z., Luo, H. et al. The effect of semi-automatic segmentation approaches on semi-quantitative parameters of 68Ga-Pentixafor PET-CT in newly diagnosed multiple myeloma patients. Clin Transl Imaging (2026). https://doi.org/10.1007/s40336-025-00745-5  January 8, 2026.  

Overview

This study looked at how best to measure disease burden on a specialized PET-CT scan used in people with newly diagnosed multiple myeloma. The scan uses a tracer called gallium-68 Pentixafor, which highlights myeloma cells by targeting a protein known as CXCR4. While this scan shows where disease is present, there is no standard method for outlining, or “segmenting,” these lesions on the images. Different approaches can give different results, which may affect how doctors estimate risk and predict outcomes.

Researchers reviewed PET-CT scans from 49 patients and tested several semi-automatic ways to outline myeloma lesions across the skeleton. These methods used different cutoffs based on how much tracer was taken up in normal organs such as the liver, spleen, or bone. Each approach was scored on how well it captured true myeloma lesions while avoiding normal tissues. The team then compared the results with bone marrow biopsy findings, visual scan staging, and whether the disease worsened within three years.

The performance of these methods varied widely. One approach, which defined lesions as areas with tracer uptake at least twice that of the liver, showed the best overall balance. It captured myeloma sites well without including too much normal tissue. Measurements from this method closely matched how much myeloma was found in the bone marrow and how advanced the disease looked on visual scan review.

Importantly, this liver-based method was also the most accurate at predicting which patients were more likely to have disease progression within three years. It performed better than more traditional methods that simply analyze the entire skeleton, although the difference was modest.

In summary, this study suggests that using twice the liver uptake as a reference is a reliable and practical way to measure total myeloma burden on gallium-68 Pentixafor PET-CT scans. This approach may help doctors better assess disease severity and future risk, supporting its use as a more standardized tool in the care of people with multiple myeloma.

"Therapeutic Potential of Exportin 1 and Aurora Kinase A Inhibition in Multiple Myeloma Cells"

Source

Okabe, S., Tanaka, Y., Otsuki, S., Moriyama, M., Yoshizawa, S., Gotoh, A., & Akahane, D. (2026). Therapeutic Potential of Exportin 1 and Aurora Kinase A Inhibition in Multiple Myeloma Cells. Hematology Reports, 18(1), 10. https://doi.org/10.3390/hematolrep18010010  January 9, 2026 

Overview

This study explored a new treatment approach for multiple myeloma and a related, more aggressive disease called plasma cell leukemia. Both conditions involve abnormal plasma cells that divide too quickly. The researchers focused on proteins called aurora kinases, especially AURKA, which help control cell division and are often overactive in cancer cells.

By analyzing patient data, the researchers found that AURKA levels were higher in myeloma cells than in normal cells and were especially high in plasma cell leukemia. Higher AURKA levels were linked to poorer outcomes, suggesting this protein may be a marker of more aggressive disease.

The team then tested drugs in laboratory-grown myeloma cells. One drug, LY3295668, blocks AURKA. Another drug, selinexor, is already approved for patients with hard-to-treat myeloma and works by blocking a process cancer cells use to survive. Each drug alone caused cancer cells to die in a dose-dependent way. When the two drugs were used together, they worked better than either one alone, leading to more cancer cell death and stronger activation of cell suicide pathways.

This combined effect was also seen in myeloma cells that were resistant to bortezomib, a commonly used myeloma drug, and in samples from plasma cell leukemia. Reducing AURKA levels directly made myeloma cells even more sensitive to selinexor, supporting the idea that AURKA plays a key role in drug resistance.

Overall, the findings suggest that blocking AURKA can weaken myeloma cells and make existing treatments like selinexor more effective, especially in high-risk or drug-resistant disease. While these results come mainly from laboratory studies, they provide a strong reason to test this drug combination further in patients, with the goal of improving outcomes for those with limited treatment options.

"A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma"

Source

Pilcher, W.C., Yao, L., Gonzalez-Kozlova, E. et al. A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma. Nat Cancer (2026). https://doi.org/10.1038/s43018-025-01072-4  January 9, 2026. 

Overview

This study explored how the immune environment in the bone marrow affects multiple myeloma, a blood cancer that remains incurable despite many treatment advances. Researchers analyzed more than 1.3 million individual cells from the bone marrow of 337 newly diagnosed patients to create a detailed “Immune Atlas” of multiple myeloma. This allowed them to map different immune and blood cell types and see how they interact with cancer cells.

The study found that specific genetic changes in myeloma cells influenced the surrounding immune system. For example, patients with a deletion called 17p13 showed unusually high activity of type 1 interferon genes in T cells and other immune cells. While interferon signaling usually helps fight cancer, in these patients it may contribute to immune dysfunction, allowing the tumor to persist. Patients whose disease progressed quickly had immune cells showing signs of aging and chronic inflammation, which can reduce the ability of T cells to attack cancer effectively.

The researchers also identified patterns of communication between immune cells and myeloma cells. Certain molecules, including BAFF and APRIL, were highly active and appeared to help cancer cells survive and grow. In rapidly progressing patients, the immune environment was more inflammatory, with myeloid cells releasing cytokines that could further support tumor growth and suppress effective immune responses.

Importantly, the study showed that combining information about the tumor’s genetic features with these immune cell patterns improved the ability to predict patient outcomes. Some patients with seemingly favorable genetics still had poor outcomes because their immune environment was inflamed or immunosenescent. This suggests that looking at both the tumor and the immune system provides a more complete picture for risk assessment and treatment planning.

In summary, this work highlights the critical role of the bone marrow immune environment in multiple myeloma. Understanding how immune cells interact with cancer cells could help identify new targets for therapy and allow more personalized treatment strategies. By integrating immune profiles with tumor genetics, doctors may better predict outcomes and select treatments that are most likely to work for each patient.

"Navigating the evolving management of smoldering multiple myeloma"

Source

Hammami, M.B., Canevarolo, R.R., Silva, A.S., Alsina, M., Kumar, N., Baz, R. and Shain, K.H. (2026), Navigating the evolving management of smoldering multiple myeloma. HemaSphere, 10: e70275. https://doi.org/10.1002/hem3.70275  January 9, 2026.

Overview

Smoldering multiple myeloma (SMM) is an intermediate stage between a benign blood condition called MGUS and full-blown multiple myeloma. Not all patients with SMM progress to symptomatic disease, but the risk varies widely, so it’s important to identify which patients are most likely to worsen. Traditional risk models relied mainly on simple clinical measures like tumor burden, but these models didn’t capture the underlying biological differences between patients.

Recent research has improved risk prediction by including genetic information, immune system features, and markers that change over time. These insights show that immune system changes and the development of new cancer cell subclones are key drivers of disease progression. Because of this, new models now combine biology, genomics, and clinical data to better forecast who might benefit from early treatment.

Clinical trials have started to challenge the old “watch-and-wait” approach, especially for high-risk SMM, by testing early therapies such as lenalidomide and daratumumab. While these drugs are approved for high-risk patients, their use in everyday practice remains debated because doctors must balance the risks of overtreatment against the dangers of waiting too long.

Currently, the recommended approach emphasizes personalized care. Participation in clinical trials is preferred, allowing patients to receive treatment guided by detailed testing and companion diagnostics. For some patients, careful observation before starting therapy is appropriate, giving time to understand the disease’s behavior. Decisions about early treatment should be individualized, factoring in patient preferences, evolving biomarkers, and the specific risk of progression.

In summary, the management of SMM is shifting from a one-size-fits-all strategy to a more nuanced, biology-driven approach. Ongoing research is focused on improving risk prediction and identifying which patients truly benefit from early intervention, while minimizing unnecessary treatment for those with lower-risk disease. This evolving strategy aims to ensure that patients receive the right therapy at the right time, improving outcomes while avoiding harm.

"Sex differences in the clinical presentation of patients with newly diagnosed multiple myeloma"

Source

Ong KL, Arnold KD, Wessel MC, et al. Sex differences in the clinical presentation of patients with newly diagnosed multiple myeloma. Cancer. 2026;e70192. doi:10.1002/cncr.70192  January 9, 2026. .

Overview

Smoldering multiple myeloma (SMM) is an intermediate stage between a benign blood condition called MGUS and full-blown multiple myeloma. Not all patients with SMM progress to symptomatic disease, but the risk varies widely, so it’s important to identify which patients are most likely to worsen. Traditional risk models relied mainly on simple clinical measures like tumor burden, but these models didn’t capture the underlying biological differences between patients.

Recent research has improved risk prediction by including genetic information, immune system features, and markers that change over time. These insights show that immune system changes and the development of new cancer cell subclones are key drivers of disease progression. Because of this, new models now combine biology, genomics, and clinical data to better forecast who might benefit from early treatment.

Clinical trials have started to challenge the old “watch-and-wait” approach, especially for high-risk SMM, by testing early therapies such as lenalidomide and daratumumab. While these drugs are approved for high-risk patients, their use in everyday practice remains debated because doctors must balance the risks of overtreatment against the dangers of waiting too long.

Currently, the recommended approach emphasizes personalized care. Participation in clinical trials is preferred, allowing patients to receive treatment guided by detailed testing and companion diagnostics. For some patients, careful observation before starting therapy is appropriate, giving time to understand the disease’s behavior. Decisions about early treatment should be individualized, factoring in patient preferences, evolving biomarkers, and the specific risk of progression.

In summary, the management of SMM is shifting from a one-size-fits-all strategy to a more nuanced, biology-driven approach. Ongoing research is focused on improving risk prediction and identifying which patients truly benefit from early intervention, while minimizing unnecessary treatment for those with lower-risk disease. This evolving strategy aims to ensure that patients receive the right therapy at the right time, improving outcomes while avoiding harm.

"Models of myeloma bone disease: In vivo and in vitro approaches"

Source

Jiaxian Wang, Sonja Zweegman, Richard W.J. Groen, Models of myeloma bone disease: In vivo and in vitro approaches, Bone, 2026, 117789, ISSN 8756-3282, https://doi.org/10.1016/j.bone.2026.117789. January 10, 2026. 

Overview

This review focuses on how researchers study myeloma bone disease (MBD), a major complication of multiple myeloma that causes bone destruction, fractures, and pain. Normally, bone health is maintained by a balance between osteoclasts, which break down bone, and osteoblasts, which build it up. In multiple myeloma, cancer cells disrupt this balance by increasing signals that activate osteoclasts and releasing factors that block osteoblasts, leading to bone loss.

To understand these processes and test new treatments, scientists use a variety of experimental models. The most established are the 5T series of mouse models, which can reproduce both bone destruction and impaired bone formation. These models are useful because they allow studies of immune interactions and drug effects, including therapies that reduce bone breakdown or stimulate bone formation, like zoledronic acid and bortezomib. Other mouse models, including humanized mice, incorporate human bone marrow cells to better mimic patient biology, while three-dimensional lab-grown systems and induced pluripotent stem cell–derived bone marrow organoids (iBMOs) offer fully human platforms for studying bone cell dynamics.

Each model has advantages and limitations. Mouse models are robust and reproducible, but species differences can make it difficult to test human-specific drugs such as denosumab. iBMOs and other human cell-based systems overcome this problem and allow patient-specific studies, but they currently lack fully mineralized bone, mature blood vessels, and adult-like cell properties. Variability in stem cell differentiation across labs also limits reproducibility.

Despite these challenges, advances in iBMO technology and 3D culture systems are moving research toward human-specific, mechanistically faithful models. These systems have the potential to reduce reliance on animals, allow personalized studies, and provide platforms for testing new therapies directly in a human bone marrow context. Together, the combination of mouse models, humanized systems, and organoids is helping researchers better understand MBD and develop treatments that address both bone destruction and cancer growth.

"Postoperative complications following total shoulder arthroplasty in multiple myeloma patients with prior bone marrow transplantation"

Source

Tera A. Scott, Randall R. Rainwater, Simon C. Mears, Benjamin M. Stronach, Jeffrey B. Stambough, C.Lowry Barnes, J.Ryan Hill, Postoperative complications following total shoulder arthroplasty in multiple myeloma patients with prior bone marrow transplantation, Seminars in Arthroplasty: JSES, 2026, 151551, ISSN 1045-4527, https://doi.org/10.1016/j.sart.2026.151551. January 10, 2026. 

Overview

This study examined the outcomes of total shoulder replacement surgery in patients with multiple myeloma, focusing on those who had previously undergone a bone marrow transplant (BMT). While BMT can significantly improve survival in myeloma, it often requires intensive chemotherapy and high-dose steroids, which can weaken the immune system, damage bones, and increase the risk of fractures. These factors, along with pre-existing bone lesions and older age, can make some patients candidates for shoulder replacement.

Using a large national insurance database, researchers compared patients with and without a history of BMT who underwent total shoulder arthroplasty (TSA). They looked at surgical complications, joint-specific issues like prosthetic infection or instability, thromboembolic events such as blood clots, follow-up medical visits, revision surgeries, and overall healthcare costs within 90 days after surgery.

The study found that myeloma patients who had received a BMT were younger at the time of surgery but had more overall health problems. They experienced higher rates of general surgical complications and significantly more blood clots compared with patients who had not had a transplant. There were no differences in joint-specific complications like infections, prosthetic instability, or periprosthetic fractures. Healthcare costs were substantially higher in the BMT group at 30, 60, and 90 days after surgery.

These findings suggest that patients with a history of BMT face higher risks and higher healthcare needs following shoulder replacement. The results highlight the importance of careful preoperative planning, close monitoring, and aggressive measures to prevent blood clots in this high-risk population, in order to optimize both safety and overall value of the procedure.

"Impact of Stem Cell Mobilization with Chemotherapy versus G-CSF Alone for Multiple Myeloma Patients with Suboptimal Response Before Autologous Stem Cell Transplant"

Source

Piyatida Chumnumsiriwath, Polina Bellman, Minh-Ha Tran, Christina Golly, Stefan O. Ciurea, Piyanuch Kongtim, Impact of Stem Cell Mobilization with Chemotherapy versus G-CSF Alone for Multiple Myeloma Patients with Suboptimal Response Before Autologous Stem Cell Transplant, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.01.004. January 11, 2026. 

Overview

This study looked at how different methods of collecting stem cells affect outcomes for multiple myeloma patients undergoing autologous stem cell transplant (ASCT), which remains a key treatment for this disease. Before the transplant, stem cells are collected from the patient’s blood, either using a growth factor called G-CSF alone or combined with chemotherapy, a process known as chemo-mobilization. Chemo-mobilization can produce more stem cells, but its effect on disease control and post-transplant outcomes in the modern treatment era was unclear.

The researchers reviewed 67 patients who underwent ASCT at their institution. About half received chemo-mobilization with cyclophosphamide or KD-PACE plus G-CSF, while the other half received G-CSF alone. Chemo-mobilization led to higher stem cell yields, required fewer collection sessions, and reduced the need for additional mobilizing drugs. It also lowered tumor burden in most patients before transplant, and a subset even had improved responses prior to ASCT.

However, 90 days after transplant, the overall response rates were similar between the two groups. Interestingly, the group that received only G-CSF had higher rates of complete remission and minimal residual disease negativity. At a median follow-up of 20 months, progression-free survival was better in the G-CSF group, although overall survival was similar between the groups. The study also found that patients who achieved a very good partial response or better before transplant had a lower risk of relapse and longer progression-free survival.

In summary, chemo-mobilization is effective at collecting more stem cells and can reduce tumor burden safely, but pre-transplant disease control is a key predictor of post-transplant outcomes. Achieving a strong response before ASCT appears critical for improving long-term progression-free survival.

"Structure-based drug design of small-molecule c-Myc G-quadruplex binders"

Source

Gao, J., Xu, C., Hong, R. et al. Structure-based drug design of small-molecule c-Myc G-quadruplex binders. J Comput Aided Mol Des 40, 46 (2026). https://doi.org/10.1007/s10822-025-00760-8  January 12, 2026. 

Overview

This study explored a new approach to targeting the c-Myc gene, which plays a key role in cancer growth, including multiple myeloma. c-Myc is a difficult target for traditional drugs because its protein structure lacks the usual binding sites, making it “undruggable.” Researchers focused instead on a specific DNA structure in the c-Myc promoter called a G-quadruplex (G4), which can naturally suppress c-Myc activity.

Using the 3D structure of the c-Myc G4, the team performed virtual screening of a large chemical library to find small molecules that could bind to this structure. They then tested promising compounds in lab experiments to see if they affected c-Myc activity. One compound, called Y502-3888, successfully bound to the G4 structure and reduced c-Myc levels at both the gene (mRNA) and protein levels.

These results suggest that Y502-3888 could serve as a foundation for developing new therapies that indirectly inhibit c-Myc in multiple myeloma. By targeting the G4 structure rather than the protein itself, this approach offers a novel strategy for controlling tumor growth in cancers driven by c-Myc.

"Multiple Myeloma Management in a Large Low- and Middle-Income Country: Lessons From India in Balancing Cost and Clinical Efficacy in Resource-Limited Settings"

Source

Prabhat Gautam Roy et al. Multiple Myeloma Management in a Large Low- and Middle-Income Country: Lessons From India in Balancing Cost and Clinical Efficacy in Resource-Limited Settings. JCO Oncol Pract 0, OP-25-00947 DOI:10.1200/OP-25-00947  January 12, 2026. 

Overview

This review examines how multiple myeloma treatment has advanced globally and the challenges of applying these advances in low- and middle-income countries (LMICs), using India as an example. In wealthier countries, the use of three-drug combinations (proteasome inhibitor plus immunomodulator plus steroid), anti-CD38 antibody-based four-drug regimens, and routine autologous stem-cell transplant (ASCT) has improved survival, with many patients living more than a decade after diagnosis.

In LMICs, however, delivering this level of care is difficult due to high out-of-pocket costs, limited transplant infrastructure, inconsistent drug supply, and unequal access to diagnostics. The review draws on international clinical trials, local real-world data, and expert consensus to provide practical guidance for these settings. It highlights that bortezomib, lenalidomide, and dexamethasone (VRd) remains the most cost-effective first-line treatment. While adding anti-CD38 antibodies can improve outcomes, these are often unaffordable. Early ASCT is emphasized as a highly effective and relatively low-cost way to deepen responses and extend progression-free survival.

For patients who relapse, antibody-free triplets such as pomalidomide-bortezomib-dexamethasone or carfilzomib-dexamethasone are effective options, while older alkylator-based regimens and salvage ASCT remain valuable when newer therapies are not accessible. Emerging immunotherapies are largely out of reach in these settings.

The review stresses the importance of equitable access strategies, including government drug procurement and patient-assistance programs, to bring global treatment advances to real-world practice in resource-limited environments. By combining clinical evidence with economic and system realities, it provides a roadmap for delivering high-value myeloma care in LMICs, balancing effectiveness, affordability, and fairness.

"A nutritional index model for predicting resistance and prognosis in multiple myeloma following autologous stem cell transplantation"

Source

Zhang, C., Miao, D., Zhang, Y. et al. A nutritional index model for predicting resistance and prognosis in multiple myeloma following autologous stem cell transplantation. Discov Onc (2026). https://doi.org/10.1007/s12672-025-04377-z  January 12, 2026. 

Overview

This study looked at how nutritional status affects outcomes in multiple myeloma patients undergoing autologous stem cell transplantation. Researchers focused on the prognostic nutritional index (PNI), which measures a patient’s nutritional and immune status and has been increasingly used to predict outcomes in cancer patients.

The team reviewed medical records of 245 patients treated at their hospital between 2011 and 2018. Using statistical analysis, they determined that a PNI score of 46.1 was the best threshold for predicting survival. Patients with a low PNI had much worse outcomes, with a three-year survival rate of just 1.0%, compared with 11.6% for those with a higher PNI.

Further analysis identified several factors that independently influenced prognosis after transplant: lactate dehydrogenase levels, PNI, disease status before transplant, extent of bone marrow involvement, and the presence of diabetes. Based on these factors, the researchers created a predictive model to help estimate individual patient outcomes.

In summary, the study shows that PNI is a valuable predictor of survival for myeloma patients undergoing autologous stem cell transplantation. Incorporating PNI into clinical assessments can help guide treatment decisions and provide patients with a clearer understanding of their expected prognosis.

"CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models"

Source

Paul Lin, Sunil Acharya, Francia Reyes-Silva, Rafet Basar, Nadima Uprety, Luz Yurany Moreno Rueda, Pei Lin, April L. Gilbert, Pinaki P. Banerjee, Dexing Fang, Chenyu Zhang, Ana Karen Nunez Cortes, Luciana Melo Garcia, May Daher, Luis Muniz-Feliciano, Gary M. Deyter, Vernikka Woods, Seema Rawal, Ping Li, Corry M. Jones, Rejeena Shrestha, Muzaffar H. Qazilbash, Krina K. Patel, Hans C. Lee, Richard E. Champlin, David Marin, Elizabeth J. Shpall, Robert Z. Orlowski, Katayoun Rezvani; CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-25-0130  January 13, 2026.  

Overview

This study investigated CD70, a protein that is highly expressed in many cancers, including multiple myeloma, and explored its potential as a treatment target. Researchers found that CD70 levels were elevated in high-risk myeloma patients, including those with the t(4;14) genetic abnormality, and that higher CD70 expression was associated with poorer survival. These findings were confirmed using multiple laboratory techniques, including single-cell RNA sequencing, flow cytometry, and tissue analysis.

The team then tested a novel therapy using natural killer (NK) cells engineered with a chimeric antigen receptor (CAR) that recognizes CD70 and includes IL-15 (CAR27/IL-15). These CAR NK cells showed strong ability to kill CD70-positive myeloma cells both in lab experiments and in mouse models. Importantly, they remained effective even when another common myeloma target, BCMA, was absent, which is relevant for patients who relapse after BCMA-directed therapy.

Overall, the study identifies CD70 as a promising new target for high-risk multiple myeloma and provides preclinical evidence supporting ongoing clinical trials testing CD70-targeting CAR NK cells. This approach could offer a new option for patients whose disease has progressed despite other treatments.

"Comparative Effectiveness and Safety of PI-Rd Triplets in Relapsed/Refractory Multiple Myeloma: INSIGHT-MM Data Analysis"

Source

N. Puig, X. Leleu, H. C. Lee, et al., “Comparative Effectiveness and Safety of PI-Rd Triplets in Relapsed/Refractory Multiple Myeloma: INSIGHT-MM Data Analysis,” European Journal of Haematology (2026): 1–13, https://doi.org/10.1111/ejh.70079.  January 13, 2025 

Overview

This study evaluated the real-world effectiveness and safety of three proteasome inhibitor (PI)–based triplet regimens—ixazomib-lenalidomide-dexamethasone (IRd), carfilzomib-lenalidomide-dexamethasone (KRd), and bortezomib-lenalidomide-dexamethasone (VRd)—in adults with relapsed/refractory multiple myeloma (RRMM) using data from the global INSIGHT-MM observational study. The analysis included 356 lines of therapy from 348 patients and assessed patient characteristics, treatment responses, and safety outcomes, with adjustments made for differences in baseline characteristics.

Results showed that median real-world progression-free survival (rwPFS) was 14.5 months for IRd, 13.2 months for KRd, and 9.1 months for VRd. After adjusting for baseline covariates, no significant differences in rwPFS were observed between regimens, and all three demonstrated manageable safety profiles. Duration of treatment and response trended longer for IRd and KRd compared with VRd, although these differences were not statistically significant after adjustment. The study also highlighted that treatment choice should consider patient- and disease-specific factors, including convenience, prior therapies, comorbidities, and geographic or healthcare system considerations, alongside efficacy and safety.

Overall, this real-world analysis supports the comparable effectiveness and safety of IRd, KRd, and VRd in RRMM and underscores the importance of individualized treatment selection. These findings complement clinical trial data and provide practical guidance for optimizing PI-based therapy in routine clinical practice.

“Trends in Smoldering Myeloma Incidence in the United States From Cancer Registries, 2012–2022"

Source

R. Wang, A. J. Davidoff, M. Schoen, et al., “Trends in Smoldering Myeloma Incidence in the United States From Cancer Registries, 2012–2022,” American Journal of Hematology (2026): 1–3, https://doi.org/10.1002/ajh.70202.  January 13, 2026.  

Overview

This study provides the first population-based estimate of smoldering multiple myeloma (SMM) incidence in the United States using newly released SEER cancer registry data. SMM, an asymptomatic plasma cell disorder, carries a 10% annual risk of progression to symptomatic multiple myeloma (MM) during the first five years after diagnosis. Patients diagnosed with MM from 2012 to 2022 were identified using the International Classification of Diseases for Oncology, 3rd edition (code 9732), and categorized into symptomatic MM, SMM, or other/unknown using SEER’s MM site-specific variable derived from pathology reports and clinician statements. Incidence rates were calculated per 100,000 person-years and age-adjusted to the 2000 US standard population. Trends were assessed using joinpoint regression analyses.

From 2012 to 2022, the overall MM incidence was 6.72 per 100,000 person-years, showing a significant increase during 2012–2019 and a non-significant decrease during 2019–2022. The mean SMM incidence was 0.69 per 100,000 person-years, increasing steadily from 0.59 in 2012 to 0.90 in 2022, representing a 50% rise over the decade. Incidence increased with age until 75–79 years and was higher in males than females, particularly after age 60. Non-Hispanic Black individuals had higher SMM incidence across all age groups compared with Non-Hispanic White and Hispanic populations.

These findings suggest that the observed increase in SMM incidence may reflect evolving diagnostic and reporting practices, greater clinical awareness, and potential contributions from environmental and lifestyle factors. Although SMM remains less common than symptomatic MM, understanding its incidence is critical for planning screening strategies and evaluating the impact of early management approaches. Limitations include the reliance on registry-based variables without detailed laboratory data and potential underdiagnosis due to the asymptomatic nature of SMM. This analysis establishes a benchmark for SMM incidence in the US and provides insight for future epidemiologic and clinical research.

“Association between systemic immune-inflammatory markers and monoclonal gammopathy of undetermined significance in the elderly population: findings from the National health and nutrition examination survey"

Source

Zhang, C., Hou, K., Lin, D. et al. Association between systemic immune-inflammatory markers and monoclonal gammopathy of undetermined significance in the elderly population: findings from the National health and nutrition examination survey. Clin Exp Med (2026). https://doi.org/10.1007/s10238-025-02022-1  January 13, 2026.  

Overview

This study investigated the relationship between systemic immune-inflammatory markers and the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in older adults. MGUS is a premalignant plasma cell disorder whose risk increases with age and may progress to multiple myeloma, with the tumor microenvironment (TME) playing a key role in disease dynamics.

A cross-sectional analysis was conducted using data from 12,080 adults aged ≥50 years, including 350 MGUS cases, from the NHANES III and 1999–2004 cycles. Multivariable logistic regression evaluated associations between MGUS and systemic immune-inflammatory markers, including lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), hemoglobin, albumin, lymphocyte, platelet score (HALP), and their individual components. Generalized additive models explored potential nonlinear relationships and threshold effects, including stratification by race.

Higher LMR quartiles were positively associated with MGUS prevalence (Q4 vs. Q1: OR = 1.454, 95% CI 1.048–2.016), whereas elevated monocyte counts (OR = 0.624, 95% CI 0.456–0.853) and albumin levels (OR = 0.446, 95% CI 0.317–0.627) were linked to reduced MGUS odds. Nonlinear analyses identified a U-shaped relationship between PLR and MGUS, and race-specific nonlinear correlations were observed for LMR, PLR, and lymphocyte counts.

These findings indicate that systemic immune-inflammatory markers are significantly associated with MGUS in older adults. They highlight the potential utility of these markers for early detection, risk stratification, and longitudinal monitoring of MGUS, providing a noninvasive window into TME dynamics.

“A Nested Case-Control Study of Monoclonal Gammopathy of Undetermined Significance in the Multiethnic Cohort Study"

Source

Maryam Salehi, Lynne R. Wilkens, Jia Yin Wan, Victoria K. Cortessis, Daniel Stram, David V. Conti, Jose Aparicio, Esther Lam, Mallory P. Bernstein, Pinkal Desai, Kimberly A Bertrand, Aaron S. Rosenberg, Lisa Lee, Loic Le Marchand, Christopher A Haiman, Jane Emerson, Wendy Cozen; A Nested Case-Control Study of Monoclonal Gammopathy of Undetermined Significance in the Multiethnic Cohort Study. Blood Adv 2026; bloodadvances.2024015266. doi: https://doi.org/10.1182/bloodadvances.2024015266  January 13, 2026.  

Overview

This study investigated racial/ethnic differences and body mass index (BMI) associations in monoclonal gammopathy of undetermined significance (MGUS) and its progression to multiple myeloma (MM) or other plasma cell neoplasms (PCN). MGUS is the obligatory precursor of MM, with African Americans experiencing ~2-fold higher incidence and Asian Americans ~50% lower incidence compared with non-Hispanic Whites.

Using a case-control study nested in the Multiethnic Cohort (MEC), 426 laboratory-confirmed MGUS cases (370 non-IgM, 56 IgM) and 863 MGUS-free controls were analyzed. Participants included Japanese American, African American, Latino, Native Hawaiian, and White individuals aged ≥65 years. Multivariable logistic regression assessed MGUS determinants, while Cox regression evaluated progression to MM or other PCN.

The distribution of immunoglobulin (Ig) isotypes differed significantly by race/ethnicity (P = 0.005), with Japanese Americans having the lowest (11.0%) and Native Hawaiians the highest (23.5%) proportion of IgA. Increasing BMI was associated with higher odds of non-IgM MGUS, with a 6% increase per BMI unit (95% CI 3–9%) across all racial/ethnic groups. Associations were strongest among Native Hawaiians (13% increase per BMI unit) and were observed particularly for IgA and IgG MGUS. In contrast, BMI was not associated with progression to MM or other PCN, which was primarily predicted by an M-spike >1.5 g/dL.

These findings indicate that BMI is a key determinant of MGUS occurrence but does not influence progression risk, while Ig isotype distributions vary across racial/ethnic groups. This underscores the importance of considering both anthropometric and demographic factors in understanding MGUS epidemiology and risk stratification.

“Prediction of ISS and R-ISS Stratification in Newly Diagnosed Multiple Myeloma Using Lumbar Spine MRI Radiomics Model: A Two-Center Multimodal Study"

Source

Hao, W., Zheng, F., Gou, X. et al. Prediction of ISS and R-ISS Stratification in Newly Diagnosed Multiple Myeloma Using Lumbar Spine MRI Radiomics Model: A Two-Center Multimodal Study. J Digit Imaging. Inform. med. (2026). https://doi.org/10.1007/s10278-025-01833-8  January 14, 2026. 

Overview

This study aimed to develop a noninvasive imaging-based approach to predict International Staging System (ISS) and Revised ISS (R-ISS) stages in newly diagnosed multiple myeloma (ndMM), addressing limitations in access to genetic testing. In this two-center retrospective analysis, 164 ndMM patients underwent lumbar MRI, and radiomics features were extracted from T1-weighted imaging (T1-WI) and T2-weighted fat-suppressed (T2-FS) sequences. Models were constructed using single-sequence and dual-sequence radiomics features, alongside a clinical baseline model. A fusion model integrating optimal radiomics features with peripheral blood biomarkers was also developed.

Model performance was assessed using AUC, accuracy, sensitivity, and specificity in training, internal validation, and external test cohorts. Independent risk factors were identified through two-step logistic regression. Comparative performance was evaluated using the DeLong test, and net reclassification improvement (NRI) was calculated to quantify improvements in risk stratification.

Among radiomics-only models, the T1-WI–based model showed the best performance for ISS prediction (AUC 0.743 internal, 0.707 external), while a cross-region radiomics model achieved the highest accuracy for R-ISS prediction (AUC 0.814 internal, 0.763 external). The fusion model significantly outperformed both the standalone radiomics and clinical models (P < 0.001), achieving the highest discriminative ability with AUCs of 0.869 (internal) and 0.825 (external), along with substantial net reclassification improvement (NRI 1.536 internal, 1.296 external).

Overall, lumbar MRI-based radiomics, particularly when combined with blood biomarkers, provides a practical and noninvasive strategy for risk stratification in ndMM, offering meaningful clinical utility in resource-limited settings where advanced genetic profiling is not readily available.

“Survival and Renal Recovery in Newly Diagnosed Multiple Myeloma Patients Presenting With Dialysis-Requiring Severe Renal Impairment”

Source

R. Sharma, E. G. Atenafu, E. Masih-Khan, et al., “Survival and Renal Recovery in Newly Diagnosed Multiple Myeloma Patients Presenting With Dialysis-Requiring Severe Renal Impairment,” European Journal of Haematology (2026): 1–8, https://doi.org/10.1111/ejh.70116.  January 14, 2026. 

Overview

This retrospective study evaluated renal recovery and survival outcomes in patients with newly diagnosed multiple myeloma (NDMM) who presented with severe renal insufficiency requiring dialysis, a population historically associated with poor prognosis. Outcomes were analyzed for 70 patients treated between 2010 and 2022, all of whom received novel agent–based induction therapy, predominantly bortezomib-based. Nearly three-quarters of patients subsequently underwent autologous stem cell transplantation (ASCT).

Overall, 48% of patients achieved dialysis independence. On univariate analysis, the only factor predicting renal recovery was early achievement of a very good partial response (VGPR) within 4.4 months of treatment initiation, which was strongly associated with dialysis withdrawal. At a median follow-up of 39 months, survival outcomes were favorable, with a median overall survival (OS) of 98.3 months and 2- and 5-year OS rates of 84% and 67%, respectively. Progression-free survival at 2 and 5 years was 66.9% and 43.7%.

Multivariable analysis identified three independent predictors of improved OS: low lactate dehydrogenase at diagnosis, receipt of ASCT, and achievement of dialysis independence. Patients who discontinued dialysis had substantially longer survival than those who remained dialysis dependent. These findings contrast sharply with outcomes reported in the pre-bortezomib era, when dialysis withdrawal rates were below 20% and median survival was typically under 18 months.

The study highlights the importance of rapid and deep hematologic response in driving renal recovery and long-term survival in NDMM patients with dialysis-requiring renal failure. High utilization of ASCT and widespread use of proteasome inhibitor–based induction likely contributed to the improved outcomes observed. Although limited by its retrospective design and potential referral bias, this analysis provides contemporary real-world benchmarks and underscores early VGPR and sustained dialysis independence as key therapeutic goals. These results serve as an important reference point as anti-CD38 monoclonal antibodies and other novel immunotherapies move into frontline treatment for this high-risk population.

“A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth”

Source

Giuseppe Taurino, Erika Griffini, Denise Toscani, Chiara Maccari, Saverio Tardito, Massimiliano G. Bianchi, Lavinia Casati, Erica Dander, Giovanna D’Amico, Roberta Andreoli, Nicola Giuliani, Ovidio Bussolati, Martina Chiu, A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth, Blood Neoplasia, 2026, 100195, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2026.100195. January 14, 2026. 

Overview

This study elucidates a previously unrecognized metabolic crosstalk between multiple myeloma (MM) cells and mesenchymal stromal cells (MSCs) within the bone marrow microenvironment. MM cells are glutamine-auxotrophic and depend on extracellular glutamine to sustain anabolic metabolism. Consistent with this dependency, the authors show that MM cells export large amounts of glutamate via the cystine–glutamate antiporter SLC7A11/xCT, thereby shaping a distinct metabolic niche characterized by glutamine depletion and glutamate accumulation.

Bone marrow MSCs, but not MM cells or mature osteoblasts, actively import extracellular glutamate through the transporter EAAT3 (SLC1A1), whose expression declines during osteogenic differentiation. In glutamate-rich conditions, undifferentiated, glutamine synthetase (GS)–positive MSCs convert glutamate into glutamine and secrete it into the microenvironment. Co-culture with MM cells further enhances this process by inducing expression of the bidirectional amino acid transporter SNAT5 (SLC38A5), consistent with increased glutamine efflux from MSCs.

Functionally, MSCs derived from either MM patients or healthy donors were able to sustain MM cell growth under low-glutamine conditions, recapitulating the in vivo metabolic niche. This supportive effect was abrogated by pharmacologic inhibition or genetic silencing of glutamate uptake or glutamine synthesis in MSCs, confirming the central role of this metabolic cycle.

Collectively, these findings define a reciprocal glutamate–glutamine exchange in the MM bone marrow microenvironment, in which MM cells extrude glutamate that MSCs recycle into glutamine, thereby fueling MM growth while simultaneously impairing osteoblast differentiation. Disruption of this niche-dependent metabolic trade-off suppresses MM cell proliferation, highlighting glutamate transport and glutamine synthesis in stromal cells as promising, microenvironment-directed therapeutic targets in multiple myeloma.

“CD4+ T cells mediate CAR-T cell-associated immune-related adverse events after BCMA CAR-T cell therapy”

Source

Ho, M., Paruzzo, L., Noll, J.H. et al. CD4+ T cells mediate CAR-T cell-associated immune-related adverse events after BCMA CAR-T cell therapy. Nat Med (2026). https://doi.org/10.1038/s41591-025-04121-8  January 15, 2026. 

Overview

This study characterizes a distinct spectrum of immune-related toxicities associated with BCMA-directed CAR T cell therapy in multiple myeloma, termed CAR T cell therapy–associated immune-related adverse events (CirAEs). Among 198 patients treated with ciltacabtagene autoleucel or idecabtagene vicleucel between June 2021 and December 2024, CirAEs occurred in 13.6% of patients and included uncommon but serious manifestations such as cranial nerve palsy, parkinsonism, and enterocolitis.

CirAEs were associated with substantially worse outcomes, conferring a more than fivefold increase in non-relapse mortality. Risk factor analysis identified treatment with ciltacabtagene autoleucel, early post-infusion lymphocyte expansion, and a higher CD4:CD8 ratio at apheresis as independent predictors of CirAE development. A notable illustrative case involved a patient who developed three distinct CirAEs in the setting of extreme CD4+ CAR T cell expansion, with in vitro data demonstrating that this hyperexpansion could be attenuated by CCR5 inhibition.

Mechanistically, tissue analyses revealed dense infiltration of CD4+ CAR T cells in all evaluable CirAE specimens, including cerebrospinal fluid during neurologic events, implicating CD4+ CAR T cells as central mediators of these toxicities. Together, these findings suggest that excessive CD4+ CAR T cell expansion and tissue trafficking contribute to CirAE pathogenesis and identify potential biomarkers for risk stratification, as well as CCR5 signaling as a candidate pathway for therapeutic intervention to mitigate these severe adverse events

“The Effectiveness of Elranatamab in the Management of Refractory Multiple Myeloma with Central Nervous System Involvement”

Source

Misaki Uemura, Atsushi Marumo, Atsushi Obata, Nana Matsumoto, Meya Li, Yuta Kaito, Yasunobu Nagata, Satoshi Wakita, Hideto Tamura, Hiroki Yamaguchi, The Effectiveness of Elranatamab in the Management of Refractory Multiple Myeloma with Central Nervous System Involvement, Internal Medicine, Article ID 6418-25, Advance online publication January 15, 2026, Online ISSN 1349-7235, Print ISSN 0918-2918, https://doi.org/10.2169/internalmedicine.6418-25   

Overview

Multiple myeloma that spreads to the central nervous system, which includes the brain and spinal cord, is very rare and is usually linked to poor outcomes. Even though newer treatments for multiple myeloma, such as CAR T-cell therapy and bispecific antibodies, have helped many patients achieve longer disease control, there is still no standard or proven treatment for cases that involve the central nervous system. Because of this, doctors do not yet fully understand how well these newer therapies work in this specific situation.

This report describes the first known case in Japan in which a patient with treatment-resistant multiple myeloma and central nervous system involvement was successfully treated with elranatamab, a type of bispecific antibody. The patient had impaired consciousness due to the disease affecting the brain, making the condition especially serious. The positive response in this case suggests that elranatamab may offer a potential treatment option for similar patients in the future, although more research and clinical experience are needed to confirm its safety and effectiveness.

“Imaging in Plasma-Cell Neoplasms: Italian Experts’ Recommendations”

Source

A. Corso, M. Marchetti, M. Galli, et al., “Imaging in Plasma-Cell Neoplasms: Italian Experts’ Recommendations,” European Journal of Haematology (2026): 1–11, https://doi.org/10.1111/ejh.70111.  January 15, 2026. 

Overview

This study looked at how imaging tests are currently used in Italy to detect bone and soft tissue damage in people with plasma cell disorders, including monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Imaging plays a key role in understanding how advanced the disease is and in deciding when treatment should begin. However, using older or less accurate imaging methods can miss important disease signs, which may delay diagnosis or lead to less effective treatment decisions.

In 2024, a national project brought together specialists from hematology and radiology centers across Italy to examine real-world imaging practices and identify obstacles to following international guidelines. Surveys and expert discussions showed that many patients were still being evaluated with imaging tools that are not sensitive enough to detect all bone or extra-bone lesions. As a result, disease severity was sometimes underestimated. To address this problem, experts developed a set of practical, evidence-based imaging recommendations tailored to the Italian healthcare system. These recommendations aim to improve early and accurate disease detection, support better treatment choices, and promote more consistent imaging practices for patients with plasma cell disorders.

“High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing”

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Anaïs Schavgoulidze, Aurore Perrot, Xavier Leleu, Titouan Cazaubiel, Marie-Lorraine Chretien, Pierre Feugier, Karim Belhadj, Salomon Manier, Murielle Roussel, Sabine Brechignac, Frédérique Orsini-Piocelle, Mohamad Mohty, Jean-Marc Schiano de Collela, Margaret Macro, Didier Adiko, Mamoun Dib, Jean Fontan, Carine Luttiau-Motard, Didier Bouscary, Laurent Pascal, Virginie Roland, François Lifermann, Jana Bakala, Lydia Montes, Céline Kennel, Philippe Rey, Valentine Richez, Faiza Keddar, Laurent Frenzel, Claire Calmettes, Carine Chaleteix, Isabelle Plantier, Emilie Chalayer, Anna Schmitt, Christophe Roul, Hélène Demarquette, Chloe Cerutti, Luka Pavageau, Laure Derrier, Hervé Avet-Loiseau, Jill Corre; High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing. Blood 2026; 147 (3): 266–275. doi: https://doi.org/10.1182/blood.2025029999 January 15, 2026. 

Overview

This study looked at how genetic changes in myeloma cells can help predict outcomes for people with newly diagnosed or relapsed multiple myeloma. Researchers used advanced genetic testing on samples from more than 8,000 patients treated between 2019 and 2024. They applied a new genomic staging system developed by international myeloma experts to better define which patients have higher-risk disease. Using this approach, about 22% of patients at diagnosis and more than one-third of patients at first relapse were classified as high risk based on their myeloma’s genetic features.

The results showed clear differences in how long patients stayed free from disease progression. People with high-risk disease had a shorter time before their myeloma worsened compared with those with standard-risk disease. Certain genetic changes, such as loss of part of chromosome 17, mutations in the TP53 gene, or specific combinations of other chromosome abnormalities, were strongly linked to poorer outcomes. Patients who had several of these high-risk genetic features did especially poorly. Importantly, traditional staging factors alone were not always able to separate high-risk from standard-risk patients as accurately as the new genomic system.

Overall, this large study confirms that genomic testing provides valuable information about prognosis in modern myeloma care. By using this consensus genomic staging system, doctors can more accurately identify patients with higher-risk disease and tailor monitoring and treatment strategies accordingly. This approach supports more personalized care and may help guide future treatment decisions for people living with multiple myeloma.

“Multimodal antigenic escape to GPRC5D-targeted T cell engagers in multiple myeloma”

Source

Lee, H., Ahn, S., Gonzales, G.A. et al. Multimodal antigenic escape to GPRC5D-targeted T cell engagers in multiple myeloma. Nat Med (2026). https://doi.org/10.1038/s41591-025-04175-8 January 15, 2026. 

Overview

This study explores why some people with multiple myeloma relapse after treatment with newer immune therapies that direct T cells to attack cancer cells. These treatments depend on recognizing a specific target on myeloma cells called GPRC5D. By closely examining the genetic and molecular features of myeloma cells from patients who relapsed after this therapy, researchers found that in more than two-thirds of cases, the cancer cells changed in ways that allowed them to escape immune attack.

The most common reason for treatment failure was that myeloma cells altered or lost the GPRC5D target. In some patients, large sections of DNA containing the GPRC5D gene were deleted, leading to complete loss of the target. In others, smaller genetic changes damaged the gene or prevented the GPRC5D protein from reaching the cell surface, making it invisible to immune cells. In some cases, the gene was still present but switched off through changes in gene regulation rather than DNA damage. Often, several different resistant cancer cell populations appeared at the same time within the same patient.

Importantly, the study also showed that different immune therapies aimed at GPRC5D do not all behave the same way. Some were better than others at recognizing altered forms of the target, suggesting that using therapies with different designs could help overcome resistance. Overall, these findings help explain why remissions may not last after certain immune treatments and point toward strategies to make future therapies more durable for people with multiple myeloma.

“MMSA-1 is regulated by Wnt/TCF4 and involved in multiple myeloma progression and invasion via RAS/RAF signaling pathway”

Source

Meng, S., Liu, H., Gu, L. et al. MMSA-1 is regulated by Wnt/TCF4 and involved in multiple myeloma progression and invasion via RAS/RAF signaling pathway. Ann Hematol 105, 11 (2026). https://doi.org/10.1007/s00277-026-06740-8  January 15, 2026.  

Overview

This study looks at a myeloma-specific gene called MMSA-1 and how it may help multiple myeloma cells grow, survive, and spread. Although MMSA-1 is known to be present mainly in myeloma cells, very little has been understood about how it works. Researchers used laboratory myeloma cells to either increase or decrease the activity of MMSA-1 and a related control protein called TCF4, which helps turn genes on and off.

The researchers found that TCF4 directly increases MMSA-1 production by binding to its gene and activating it. When MMSA-1 levels were higher, myeloma cells became more aggressive. MMSA-1 interacted with a protein called RAS, which is known to drive cancer growth. This interaction overstimulated several key growth pathways inside the cells, leading to faster cell growth, improved survival, and resistance to normal cell death. These changes made the myeloma cells better able to form new cancer colonies.

The study also showed that high levels of MMSA-1 changed how myeloma cells interact with their surrounding bone marrow environment. The cells became less attached to nearby tissues, which may help them spread more easily. At the same time, they released more substances that promote the formation of new blood vessels, which can help tumors grow. Overall, these findings suggest that MMSA-1 plays an important role in making myeloma more aggressive and may represent a future target for treatments aimed at slowing disease progression.

“Actionable Steps to Address Disparities in Healthcare Among US Patients With Multiple Myeloma: A Patient Perspective"

Source

Gilbert, O., Aiello, J., Omel, J. et al. Actionable Steps to Address Disparities in Healthcare Among US Patients With Multiple Myeloma: A Patient Perspective. J Canc Educ (2026). https://doi.org/10.1007/s13187-025-02798-6  January 16, 2026. 

Overview

This article describes discussions from two U.S. Multiple Myeloma Health Equity Summits that brought together patients with multiple myeloma, patient advocates, healthcare providers, and industry representatives to talk about unfair differences in care. The goal was to better understand why some patients face delays in diagnosis or have trouble getting the best treatment, and to identify practical ways to improve care for everyone.

One major issue identified was a lack of awareness about multiple myeloma and its symptoms, especially among non-specialist healthcare providers and patients. Because early symptoms can be vague, such as fatigue or pain, many patients experience delayed diagnosis. Participants agreed that better education and training for healthcare providers could help myeloma be recognized sooner. They also emphasized the importance of clear, personalized information for patients, using multiple communication channels such as community programs, support groups, and community health workers to help patients and families understand the disease and advocate for themselves.

Another key focus was improving access to high-quality care. Participants discussed how factors like where a person lives, their financial situation, and cultural barriers can limit access to myeloma specialists and advanced treatments. Suggested solutions included expanding telehealth services, addressing possible bias in referral patterns, and using patient navigators to help people manage insurance and other logistical challenges. The group also discussed improving how clinical trials are explained to patients so they are seen as a realistic and valuable option.

Overall, the summits highlighted real-world barriers that many people with multiple myeloma face and offered clear, actionable steps for healthcare providers and policymakers. By improving education, communication, and access to care, these efforts aim to reduce long-standing inequities and ensure that all patients have a better chance to receive timely, effective treatment.

“Comparative Efficacy of Daratumumab Based Regimens in Patients With Relapsed-Refractory Multiple Myeloma (RRMM) Aged 70 and Above: A Multicenter Study"

Source

R. Mansour, K. M. Green, C. Graf, et al., “Comparative Efficacy of Daratumumab Based Regimens in Patients With Relapsed-Refractory Multiple Myeloma (RRMM) Aged 70 and Above: A Multicenter Study,” European Journal of Haematology (2026): 1–11, https://doi.org/10.1111/ejh.70077.  January 16, 2026. 

Overview

This study looked at treatment options for people aged 70 and older who have multiple myeloma that has come back or no longer responds to treatment. Older adults often face extra challenges with cancer therapy because of age-related changes in the body and a higher risk of side effects. Two commonly used daratumumab-based treatment combinations were compared to better understand how they perform in this age group.

Researchers reviewed medical records from several centers and compared daratumumab with pomalidomide and dexamethasone to daratumumab with carfilzomib and dexamethasone. Both treatments helped a similar number of patients, with about three out of four people responding to therapy. However, the combination that included carfilzomib led to deeper responses, meaning the cancer was reduced to very low levels more often. Even so, the time patients lived without their disease worsening and overall survival were similar between the two treatment groups.

The study also found that patients with poorer overall health or higher-risk genetic features tended to have worse outcomes, regardless of which treatment they received. Overall, the results suggest that both treatment options can be effective for older adults with relapsed or refractory multiple myeloma. Choosing the best therapy should be based on each patient’s overall health, prior treatments, and personal circumstances, rather than on small differences in treatment effectiveness alone.

“Inhibition of SDE2 Promotes Autophagy-Dependent Ferroptosis in Multiple Myeloma"

Source

Liang Xia, Jing Bao, Xiao-wen Chen, Yu-Chen Zhao, Xiang Wang, Yu Zheng, Inhibition of SDE2 Promotes Autophagy-Dependent Ferroptosis in Multiple Myeloma, Redox Biology, 2026, 104007, ISSN 2213-2317, https://doi.org/10.1016/j.redox.2026.104007. January 16, 2026.  

Overview

Multiple myeloma is a blood cancer that is difficult to cure because it often comes back after treatment. Scientists are still learning why myeloma cells survive and grow despite therapy. This study focused on a protein called SDE2, which is found at high levels in many people with multiple myeloma and is linked to worse outcomes.

The researchers found that SDE2 helps myeloma cells stay alive and spread by blocking two important cell “self-destruct” processes called autophagy and ferroptosis. Autophagy is a recycling system that helps cells remove damaged parts, while ferroptosis is a type of cell death linked to iron and oxidative stress. SDE2 interferes with these processes by breaking down another key protein, ATG5, which is needed for autophagy to work properly. When autophagy is blocked, ferroptosis is also reduced, allowing cancer cells to survive and multiply.

When scientists lowered SDE2 levels in myeloma cells, ATG5 levels recovered, autophagy restarted, and cancer cells became more likely to die through ferroptosis. In lab and animal studies, combining SDE2 suppression with drugs that activate autophagy led to stronger cancer control than either approach alone. These findings suggest that targeting SDE2, especially together with treatments that boost autophagy, could be a promising new strategy for treating multiple myeloma and possibly other cancers in the future.

“A Call for Compassion: How You Can Help Get Multiple Myeloma Added to the Social Security Administration’s Compassionate Allowances List"

Source

Akshay Mehta, Matthew Kaczynski, Sarah Addision, Michael J. Slade, Mark A. Fiala, A Call for Compassion: How You Can Help Get Multiple Myeloma Added to the Social Security Administration’s Compassionate Allowances List, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.01.009. January 16, 2026. 

Overview

Multiple myeloma is a serious blood cancer that affects many parts of a person’s life, not just their health. People living with myeloma often experience severe fatigue, pain, infections, and other treatment side effects that make it hard or impossible to keep working. Because of this, many patients must rely on Social Security Disability Insurance to pay for basic living costs and medical care during their illness.

Unfortunately, applying for disability benefits is often slow and stressful. Many people are denied at first and must wait months or even years for approval, adding financial strain at a time when they are already coping with a serious disease. The Social Security Administration has a special program called the Compassionate Allowances List that speeds up disability decisions for conditions that clearly meet disability requirements. While several blood cancers are included in this program, multiple myeloma is not, even though it causes similar levels of illness, treatment side effects, and long-term disability.

This article explains why multiple myeloma should be added to the Compassionate Allowances List. It highlights how the disease and its treatments limit daily functioning and ability to work, and it shares patient experiences that show the real-world impact of delayed financial support. The authors argue that current disability policy does not reflect the medical reality of myeloma. They also describe practical ways patients, caregivers, doctors, and advocates can work with the Social Security Administration to push for change, with the goal of helping people with multiple myeloma access disability benefits more quickly and with less hardship.

“Regulation of stress tolerance by CREB1 sustains multiple myeloma cell survival"

Source

Kudalkar, R., Altom, J., Galloway, J. et al. Regulation of stress tolerance by CREB1 sustains multiple myeloma cell survival. Cell Death Dis 17, 46 (2026). https://doi.org/10.1038/s41419-025-08246-z  January 16, 2026. 

Overview

Multiple myeloma is a cancer of plasma cells, which normally make antibodies to help fight infections. In myeloma, these cancer cells produce very large amounts of abnormal antibodies, creating constant stress inside the cells. To survive, myeloma cells must activate special systems that help them manage damage from toxins, misfolded proteins, and oxidative stress. Understanding how myeloma cells cope with this stress can reveal new ways to treat the disease.

This study focuses on a protein called CREB1, which helps myeloma cells survive under stressful conditions. The researchers found that CREB1 controls several key pathways that protect myeloma cells, including systems that clear harmful molecules, manage protein overload, and regulate cell recycling (called autophagy). Patients whose myeloma cells have high levels of CREB1 also show stronger activation of stress-tolerance pathways, suggesting their cancer cells are better equipped to survive harsh conditions and treatment.

The study also identified an important partner protein called TXNIP, which is often increased in patients with a high-risk form of myeloma. TXNIP helps cancer cells manage stress but also appears to be a weakness. When TXNIP was blocked, myeloma cells were no longer able to properly handle stress and began to die. These findings suggest that targeting CREB1 or TXNIP could disrupt the cancer cells’ survival systems and offer new treatment options, especially for patients with more aggressive or high-risk multiple myeloma.

“Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma"

Source

Ludwig, H., Terpos, E., Boccadoro, M. et al. Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. Ann Hematol 105, 26 (2026). https://doi.org/10.1007/s00277-026-06811-w  January 17, 2026. 

Overview

Plitidepsin is a cancer-fighting compound derived from a marine organism. In patients with relapsed or refractory multiple myeloma, it has been tested in combination with low-dose dexamethasone (P + LD-DXM). Since no direct head-to-head trial compared this combination to the standard therapy of pomalidomide plus low-dose dexamethasone (POM + LD-DXM), researchers used patient data from previous pomalidomide studies to make a matched comparison.

The analysis showed that plitidepsin plus dexamethasone performed similarly to pomalidomide plus dexamethasone in terms of overall survival—median survival was 11.8 months versus 13.9 months, indicating that plitidepsin is non-inferior. Importantly, plitidepsin had a more favorable safety profile: patients experienced fewer severe blood-related side effects like neutropenia and thrombocytopenia, and fewer serious infections. However, gastrointestinal side effects, muscle enzyme elevations, and muscle pain were more common with plitidepsin.

Overall, this comparison suggests that plitidepsin plus low-dose dexamethasone is an effective alternative therapy for relapsed or refractory multiple myeloma, offering similar survival benefits to pomalidomide while potentially reducing certain hematological and infection-related risks.

“Long non-coding RNAs and therapeutic resistance in multiple myeloma: from molecular insights to clinical applications"

Source

Safari, M.H., Farahani, N., Faghih Ojaroodi, A. et al. Long non-coding RNAs and therapeutic resistance in multiple myeloma: from molecular insights to clinical applications. Clin Exp Med (2026). https://doi.org/10.1007/s10238-025-02015-0  January 18, 2026.  

Overview

This review focuses on long non-coding RNAs (lncRNAs) in multiple myeloma (MM), a blood cancer caused by abnormal plasma cell growth in the bone marrow. Despite advances in therapy, drug resistance remains a major challenge. LncRNAs—regulatory RNA molecules that do not code for proteins—play important roles in MM biology by influencing disease progression and response to treatment. They regulate key processes such as miRNA sponging, epigenetic modifications, apoptosis, and major signaling pathways including PI3K/Akt and STAT3.

The review also highlights emerging therapeutic strategies targeting lncRNAs. These include RNA-based therapies, CRISPR/Cas9 gene-editing approaches, and exosome-mediated delivery systems, which may help overcome drug resistance and improve patient outcomes. By linking molecular mechanisms with clinical applications, the review underscores the potential of lncRNAs both as biomarkers and as novel treatment targets, providing a roadmap for future research in MM.

“Normal SFLC Ratio in Newly Diagnosed Myeloma: A Potential Biomarker of Non-High-Risk and Nonaggressive Disease"

Source

M. K. Singh, Y. Sanjeev, A. Pandey, et al., “Normal SFLC Ratio in Newly Diagnosed Myeloma: A Potential Biomarker of Non-High-Risk and Nonaggressive Disease,” International Journal of Laboratory Hematology (2026): 1–9, https://doi.org/10.1111/ijlh.70058.  January 19, 2026. 

Overview

This prospective study investigated the prognostic significance of baseline normal or near-normal serum free light chain (SFLC) ratios in patients with plasma cell proliferative disorders, focusing on multiple myeloma (MM). Flow cytometric immunophenotyping and interphase FISH analysis of bone marrow aspirates were performed for all newly diagnosed patients, who were also risk-stratified according to ISS, R-ISS, and R2-ISS criteria. Outcomes were assessed at least three months after initiation of standard 3- or 4-drug induction therapy.

Among 306 enrolled patients, 240 had MM, of whom 23 (9.6%) had normal SFLC ratios (n_SFLC) and 217 (90.4%) had abnormal SFLC ratios (ab_SFLC). IgG lambda M-protein was more common in n_SFLC patients, and none of these patients had circulating plasma cells. Notably, n_SFLC patients lacked TP53 deletions and other high-risk cytogenetic abnormalities. Treatment outcomes showed that 88.9% of n_SFLC patients achieved ≥VGPR compared with 65.4% of ab_SFLC patients.

These findings suggest that MM patients with a normal SFLC ratio are enriched for non–high-risk genetic features and exhibit less aggressive disease, supporting the potential of SFLC ratio as a biomarker for favorable prognosis.

“Screening for monoclonal gammopathies in the adult population of Uruguay"

Source

Eloísa Riva, Lucía Pérez, David Israel Garrido, Alicia Olascoaga, Felipe Lemos, Antonella Acerbis, Ana Vallega, Jacqueline Zipitría, Andrea Trucido, Gabriela Villanueva, Nahir Correa, Raquel Ballesté, Nicolás Marchetti, Andrea Urbin, Nadia Krul; Screening for monoclonal gammopathies in the adult population of Uruguay. Blood Global Hematology 2026; 100061. doi: https://doi.org/10.1016/j.bglo.2026.100061 January 19, 2026. 

Overview

This population-based study assessed the prevalence of monoclonal gammopathies (MGs) in Uruguayan adults, providing the first epidemiological data for this population. Between October 2021 and October 2022, 3,905 individuals aged >40 years from private and public healthcare centers were screened using blood protein analysis to detect MGUS, smoldering multiple myeloma (SMM), and multiple myeloma (MM).

The prevalence rates were 2.45% for MGUS, 0.02% for SMM, and 0.07% for MM. All patients with active disease were offered early treatment according to international guidelines, and none exhibited organ damage at diagnosis. Consistent with prior studies, advancing age (>55 years) was strongly associated with increased MGUS prevalence, supporting age-targeted screening approaches.

These findings highlight the utility of population screening for early identification of plasma cell disorders and provide a foundation for public health planning in Uruguay, facilitating timely diagnosis, intervention, and improved healthcare resource allocation.

“Multiple Myeloma Derived Sulfur Dioxide Drives CAR-T Cell Exhaustion By Inducing Mitochondrial Dysfunction"

Source

Zhengyu Yu, Hua Lin, Jingran He, Linfeng Li, Zhongwang Wang, Kun Li, Ting Niu, Binquan Qiu, Multiple Myeloma Derived Sulfur Dioxide Drives CAR-T Cell Exhaustion By Inducing Mitochondrial Dysfunction, Redox Biology, 2026, 104040, ISSN 2213-2317, https://doi.org/10.1016/j.redox.2026.104040. January 19, 2026. 

Overview

This population-based study assessed the prevalence of monoclonal gammopathies (MGs) in Uruguayan adults, providing the first epidemiological data for this population. Between October 2021 and October 2022, 3,905 individuals aged >40 years from private and public healthcare centers were screened using blood protein analysis to detect MGUS, smoldering multiple myeloma (SMM), and multiple myeloma (MM).

The prevalence rates were 2.45% for MGUS, 0.02% for SMM, and 0.07% for MM. All patients with active disease were offered early treatment according to international guidelines, and none exhibited organ damage at diagnosis. Consistent with prior studies, advancing age (>55 years) was strongly associated with increased MGUS prevalence, supporting age-targeted screening approaches.

These findings highlight the utility of population screening for early identification of plasma cell disorders and provide a foundation for public health planning in Uruguay, facilitating timely diagnosis, intervention, and improved healthcare resource allocation.

“Time to Revise Myeloma Diagnostic Criteria? A Decade of Accumulated Evidence on Serum Free Light Chain Ratio ≥100"

Source

Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin; Time to Revise Myeloma Diagnostic Criteria? A Decade of Accumulated Evidence on Serum Free Light Chain Ratio ≥100. Blood 2026; blood.2025031907. doi: https://doi.org/10.1182/blood.2025031907  January 20, 2026. 

Overview

This commentary examines the use of serum free light chain (sFLC) ratio ≥100 as a standalone myeloma-defining biomarker, introduced by the International Myeloma Working Group (IMWG) in 2014 based on early studies suggesting an ~80% risk of progression to overt multiple myeloma within 2 years. However, subsequent population-based and clinical data indicate a substantially lower progression risk, with registry data showing only a 30.4% 2-year risk, and an especially low 13.5% 2-year risk in patients with sFLC ratio ≥100 but 24-hour monoclonal proteinuria <200 mg. These patients also have minimal risk of irreversible renal damage.

The current inclusion of sFLC ≥100 in composite progression-free survival endpoints for early intervention trials in high-risk smoldering multiple myeloma may lead to misclassification of biochemical changes as clinically meaningful events. The authors advocate for revising diagnostic criteria to remove sFLC ratio ≥100 as a standalone myeloma-defining event and recommend excluding these patients from newly diagnosed myeloma trials. Instead, they should be enrolled in prospective studies focusing on therapeutic strategies for high-risk smoldering myeloma and monitored with modern imaging to better characterize their natural history in the contemporary era.