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 2025 edition.

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

In the Journals (Key Myeloma Research in January 2025)

"Radiation for Multiple Myeloma in the Era of Novel Agents: Indications, Safety, and Dose Selection, Seminars in Radiation Oncology"

Source

Samuel C. Zhang, Leslie K. Ballas, Radiation for Multiple Myeloma in the Era of Novel Agents: Indications, Safety, and Dose Selection, Seminars in Radiation Oncology, Volume 35, Issue 1, 2025, Pages 87-98,ISSN 1053-4296, https://doi.org/10.1016/j.semradonc.2024.10.004.  January 2025.  

Overview

Palliative radiotherapy (RT) remains an essential component in the management of multiple myeloma (MM), complementing advancements in systemic therapies. Over the past decade, novel drugs and stem cell transplantation have significantly improved survival rates for MM patients. However, RT continues to play a critical role in addressing symptoms like pain, preventing fractures, and relieving spinal cord compression. This review highlights the evolving role of RT in the era of biologic therapies and personalized treatment strategies.  

RT can be safely integrated with biologic therapies, including proteasome inhibitors, immunomodulators, and monoclonal antibodies. However, close monitoring is essential, particularly for heavily pre-treated patients with reduced bone marrow reserves, to mitigate potential side effects. Tailoring RT to individual needs involves considering treatment goals, such as pain control or fracture prevention, alongside lesion characteristics and the patient’s overall health and prior treatments. A personalized approach ensures that the benefits of RT are maximized while minimizing risks.  

Additionally, RT serves as a valuable bridging therapy for patients undergoing chimeric antigen receptor (CAR) T-cell therapy. It can address urgent issues like spinal cord compression or impending fractures, providing stability before initiating CAR T-cell treatment. This review underscores the importance of integrating palliative RT thoughtfully within the broader treatment landscape for MM, ensuring its use is carefully balanced and adapted to each patient’s unique circumstances.  

 

 

"Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth"

Source

Yao Y, Deng S, Ng JF, Yuan M, Chakraborty C, JoyWeiler V, Munshi N, Fulciniti M. Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth. Haematologica 2025;110(1):153-162; https://doi.org/10.3324/haematol.2024.285491.  January 2025. 

Overview

Multiple myeloma (MM) is a cancer of plasma cells that remains incurable despite recent treatment advances. This highlights the need for new, effective therapies. Researchers have found that blocking a protein called CDK7 disrupts key cell cycle and metabolic processes in MM, making it a promising target. Since CDK7 and another protein, BRD4, regulate MM through different pathways, combining inhibitors for both showed stronger results than targeting either one alone.  

This combination therapy significantly reduced MM cell growth, increased cell death, and was more effective than single-agent treatments in lab studies and patient samples. The approach also worked well against Waldenström macroglobulinemia (WM), another type of cancer, and showed similar results with other treatments that block the E2F1 pathway. Studies in animal models confirmed that dual inhibition disrupts critical cancer-driving processes, slowing tumor growth and progression. These findings suggest that targeting CDK7 and BRD4 together could be a powerful new strategy for treating MM and WM.

 

 

"Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial"

Source

Mina, Roberto et al. Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial. The Lancet Haematology, Volume 12, Issue 1, e45 - e56. January 2025.  

Overview

The CARTITUDE-4 study compared the CAR-T therapy ciltacabtagene autoleucel (cilta-cel) to standard treatments in patients with relapsed, lenalidomide-refractory multiple myeloma. In addition to improving progression-free survival, cilta-cel also demonstrated significant benefits in patient-reported outcomes, including quality of life (QoL) and symptom management.  

Patients treated with cilta-cel experienced a longer time before symptoms worsened (median of 23.7 months vs. 18.9 months with standard care) and reported greater improvements in health-related QoL. After 12 months, cilta-cel patients had notable gains in global health status (+10.1 points) and overall health scores (+8.0 points), while standard care patients saw little to no improvement. Rates of clinically meaningful improvements in QoL were also higher with cilta-cel.  

These results confirm that cilta-cel not only delays disease progression but also enhances patients' quality of life, further supporting its use as an effective treatment for lenalidomide-refractory multiple myeloma.

 

 

"Comparing the clinical trial efficacy versus real-world effectiveness of treatments for multiple myeloma: a population-based study"

Source

Visram A, Chan KK-W, Seow H, Pond G, Gayowsky A, Mohyuddin GR, McCurdy A, Sandhu I, Venner C, Lancman G, Balitsky A, Kouroukis T, Bruins R, Kumar S, Fonseca R, Mian H. Comparing the clinical trial efficacy versus real-world effectiveness of treatments for multiple myeloma: a population-based study. Haematologica 2025;110(1):228-233; https://doi.org/10.3324/haematol.2024.285768.  January 2025. 

Overview

Real-world (RW) patients with multiple myeloma (MM) often face worse outcomes than participants in clinical trials. This study compared outcomes between RW patients and those in randomized controlled trials (RCTs) for seven standard-of-care (SoC) treatments in Ontario, Canada. Researchers analyzed data from RCTs conducted between 2013 and 2021 and RW data from Ontario’s universal healthcare system covering the same period. Progression-free survival (PFS) and overall survival (OS) were compared, using “time to next treatment” (TTNT) as a proxy for PFS in the RW cohort.  

The results showed significant differences. RW patients had a 51% higher risk of disease progression or death compared to RCT participants, with the gap being most pronounced in relapsed/refractory MM regimens. Median PFS in the RW group was 7.2-18.3 months shorter than in RCTs, while median OS was 19.3-37.9 months shorter, corresponding to a 76% higher risk of death. RW patients were typically older, had more comorbidities, and were more likely to have received prior treatments, reflecting the more complex and less controlled nature of real-world clinical practice.  

The disparity stems from several factors, including the strict selection criteria of RCTs, which often exclude patients with aggressive disease, advanced age, or comorbidities. Additionally, RW patients may face challenges like lower treatment adherence, reduced dosing, or delays in starting next-line therapies. The study also noted that the Canadian healthcare system’s publicly funded structure might limit access to certain therapies, further influencing outcomes.  

This research demonstrates the need for more inclusive and pragmatic trial designs that better reflect real-world conditions. It also highlights the importance of ongoing evaluation of RW data to provide a fuller understanding of treatment effectiveness. These findings can help patients and clinicians make better-informed decisions while guiding efforts to close the gap between trial efficacy and real-world outcomes.  

 

 

"A phase I study of MAGE-A1-targeted T1367 T-cell receptor based cell therapy in patients with advanced multiple myeloma"

Source

Krüger J, Obenaus M, Blau IW, Hoser D, Vaegler M, Rauschenbach H, Anagnostopoulos I, Jöhrens K, Scheuplein V, Kieback E, Böhme J, von Brünneck A-C, Krönke J, Busse A, Willimsky G, Blankenstein T, Pezzutto A, Keller U, Nogai A. A phase I study of MAGE-A1-targeted T1367 T-cell receptor based cell therapy in patients with advanced multiple myeloma. Haematologica 2025;110(1):244-250; https://doi.org/10.3324/haematol.2024.286124.  January 2025. 

Overview

MAGE-A1 is a cancer/testis (C/T) antigen typically silent in healthy tissues but active in various cancers, including multiple myeloma (MM). This study highlights MAGE-A1's potential as a therapeutic target for advanced MM, particularly in patients with relapsed or refractory disease. Researchers analyzed 252 samples from 213 MM patients and found that 27% had significant MAGE-A1 expression (≥30% positive MM cells). Interestingly, MAGE-A1 levels increased during disease relapse and were associated with advanced conditions like extramedullary disease (EMD) and poorer survival outcomes. Patients with high MAGE-A1 expression had a significantly reduced two-year survival rate compared to those without.

The study also explored T-cell receptor (TCR) therapy targeting MAGE-A1. Researchers developed TCR-1367 T cells and tested them in a phase I trial involving two MM patients. While the therapy was well-tolerated, its effectiveness was limited at the tested dose. One patient showed a temporary decrease in MAGE-A1-positive MM cells, while the other experienced disease progression. The trial was closed early due to competing studies and challenges in recruitment.

These findings underline the need for new therapeutic approaches in MM. MAGE-A1 is a promising target, especially as current therapies face resistance linked to antigen loss. Further clinical trials are needed to explore the full potential of MAGE-A1-directed TCR therapy and its role in treating heavily pretreated MM patients

 

 

"The Burden of Multiple Myeloma in China: Trends from 1990 to 2021 and Forecasts for 2050"

Source

Xuelin Dou, Guixiang Duan, Yanting Zhong, Yang Liu, Nan Peng, Lei Wen, Jinlei Qi, Maigeng Zhou, Xiaohui Zhang, Jin Lu, The Burden of Multiple Myeloma in China: Trends from 1990 to 2021 and Forecasts for 2050, Cancer Letters, 2025, 217440, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2025.217440. January 2, 2025. 

Overview

Multiple myeloma (MM) continues to grow as a significant health concern in China, with an increasing disease burden over the past three decades. A recent study analyzed data from 1990 to 2021 and projected trends through 2050. In 2021, China recorded approximately 17,250 new MM cases and 12,984 deaths. The age-standardized rates per 100,000 population for incidence, mortality, and prevalence were 0.8, 0.6, and 2.2, respectively, with the highest burden in provinces with greater economic wealth.

From 1990 to 2021, MM incidence and mortality increased by 3.1% and 2.2%, while prevalence rose by 5.8%, highlighting advances in treatment that have extended survival. Notably, younger populations experienced a faster rise in disease burden compared to older adults, and 5.5% of MM deaths in 2021 were linked to high body mass index.

Projections for 2050 suggest that the upward trend in MM burden will persist. These findings underscore the growing impact of MM in China and emphasize the need for targeted prevention, improved treatments, and strategic healthcare planning to address this escalating challenge.

 

 

"Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis"

Source

Rahul Banerjee, Rachael Sexton, Andrew J. Cowan, Aaron S. Rosenberg, Sikander Ailawadhi, S. Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G. M. Durie, Paul G. Richardson, Saad Z. Usmani, Antje Hoering, Robert Z. Orlowski, Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis, Blood, Volume 145, Issue 1, 2025, Pages 75-84, ISSN 0006-4971, https://doi.org/10.1182/blood.2024025939. January 2, 2025. 

Overview

Dexamethasone is a key medication used to treat newly diagnosed multiple myeloma (NDMM), but it often comes with side effects like insomnia and high blood sugar. The ECOG E4A03 trial showed that a lower dose of 40 mg per week resulted in lower mortality compared to higher doses. However, the effect of reducing dexamethasone below this threshold on survival and progression-free survival (PFS) in NDMM had not been fully studied until now. To address this, researchers looked at data from two trials, SWOG 0777 and SWOG 1211, where patients received lenalidomide and dexamethasone with or without other treatments. 

In these trials, patients were either given a full dose of dexamethasone or a reduced dose, depending on the severity of their side effects. The study found that more than 60% of patients in both trials required a reduction in their dexamethasone dose, yet no significant difference was observed in PFS or overall survival (OS) between the two groups. This suggests that reducing dexamethasone may not affect survival outcomes for most patients. The study also identified a few factors that could predict better outcomes, including treatment arm, age over 70, and low platelet count.

The researchers noted that dexamethasone dose reductions are common in clinical trials, even when not encouraged by the trial protocols. Although higher doses of dexamethasone can be effective, they come with significant risks of side effects, such as hyperglycemia and muscle breakdown, which can affect patients' quality of life. Given these findings, the study suggests that further research is needed to better understand how lower doses of dexamethasone might still be effective in treating multiple myeloma without causing excessive toxicity.

This analysis provides valuable insights into how dexamethasone dosing can be managed during NDMM induction therapy. While reducing the dose does not appear to negatively impact survival, the potential for fewer side effects is significant. As new treatments for multiple myeloma emerge, it is important to continue exploring the best ways to balance effectiveness with minimizing patient harm.

 

 

"Down with dex!"

Source

Susan Harding, Joseph Mikhael, Down with dex!, Blood, Volume 145, Issue 1, 2025, Pages 3-4, ISSN 0006-4971, https://doi.org/10.1182/blood.2024026814.  January 2, 2025. 

Overview

In a recent study published in *Blood*, Banerjee and colleagues analyzed data from two major clinical trials (SO777 and S1211) to investigate the effects of reducing dexamethasone doses in patients with newly diagnosed multiple myeloma (NDMM). The results showed that lowering the dose of dexamethasone did not negatively impact key outcomes, such as progression-free survival (PFS) and overall survival (OS), which suggests that reducing dexamethasone could be an effective way to minimize toxic side effects without compromising treatment success.

Dexamethasone has been a staple in treating multiple myeloma, but its high doses are linked to serious side effects like insomnia, heartburn, muscle weakness, and hyperglycemia. As new treatments for myeloma have emerged, there’s been growing interest in whether dexamethasone is still as necessary, especially since these side effects can interfere with patients’ ability to continue their treatment. Research, including the ECOG E4A03 trial, has shown that lower doses of dexamethasone may be just as effective, leading to changes in dosing strategies.

Banerjee’s study adds to the growing evidence supporting dexamethasone-sparing strategies, particularly in patients with multiple myeloma who experience severe side effects. The findings revealed that fewer than one-third of patients in clinical trials were able to tolerate the full dose of dexamethasone. Furthermore, the analysis demonstrated that reducing the dose did not result in worse survival outcomes, suggesting that adjusting the dosage based on individual patient needs and side effects could improve the quality of life without compromising treatment effectiveness.

The study encourages the adoption of dexamethasone dose reductions as part of personalized treatment plans for multiple myeloma. By managing the drug’s side effects, patients may be able to continue treatment with fewer disruptions and better overall well-being. This growing body of evidence highlights the need for further research into the optimal role and dosage of dexamethasone in modern myeloma therapy.

 

 

"Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma"

Source

Surbhi Sidana, Krina K. Patel, Lauren C. Peres, Radhika Bansal, Mehmet H. Kocoglu, Leyla Shune, Shebli Atrash, Kinaya Smith, Shonali Midha, Christopher Ferreri, Binod Dhakal, Danai Dima, Patrick Costello, Charlotte Wagner, Ran Reshef, Hitomi Hosoya, Lekha Mikkilineni, Djordje Atanackovic, Saurabh Chhabra, Ricardo Parrondo, Omar Nadeem, Hashim Mann, Nilesh Kalariya, Vanna Hovanky, Gabriel De Avila, Ciara L. Freeman, Frederick L. Locke, Melissa Alsina, Sandy Wong, Megan Herr, Myo Htut, Joseph McGuirk, Douglas W. Sborov, Jack Khouri, Thomas Martin, Murali Janakiram, Yi Lin, Doris K. Hansen; Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma. Blood 2025; 145 (1): 85–97. doi: https://doi.org/10.1182/blood.2024025945  January 2, 2025. 

Overview

Ciltacabtagene autoleucel (cilta-cel) is a treatment for relapsed/refractory multiple myeloma (RRMM), approved in 2022. A study looked at the outcomes of cilta-cel in real-world patients who received the treatment at 16 US academic centers between March and December 2022. Of the 255 patients who underwent leukapheresis (a process to collect cells for cilta-cel), 236 (92.5%) received the treatment, with more than half not meeting the strict criteria from the CARTITUDE-1 trial. 

The study found that 75% of patients experienced cytokine release syndrome (CRS), a common side effect, with 5% having severe CRS. Neurotoxicity occurred in 14% of patients, with 4% experiencing severe effects. The response rates were high: 89% of patients had an overall response, and 70% achieved a complete response. For patients who received cilta-cel that met the CARTITUDE-1 criteria, these rates were even higher. The median progression-free survival (PFS) was not reached after a median follow-up of 13 months, but 68% of patients were still progression-free at 12 months. 

The study also found that certain factors, like high ferritin levels, high-risk genetic changes, and extramedullary disease (disease outside the bone marrow), were linked to shorter PFS. There were some concerns, including a 10% rate of nonrelapse mortality, mostly due to infections, and 5.5% of patients developing second cancers, with a small percentage having myeloid cancers. Overall, cilta-cel showed strong effectiveness in treating RRMM, even in patients who did not meet the clinical trial criteria.

 

 

"Peroxiredoxin 6 maintains mitochondrial homeostasis and promotes tumor progression through ROS/JNK/p38 MAPK signaling pathway in multiple myeloma"

Source

Gao, D., Lv, Y., Hong, F. et al. Peroxiredoxin 6 maintains mitochondrial homeostasis and promotes tumor progression through ROS/JNK/p38 MAPK signaling pathway in multiple myeloma. Sci Rep 15, 70 (2025). https://doi.org/10.1038/s41598-024-84021-y  January 2, 2025.  

Overview

Peroxiredoxin 6 (PRDX6) is an enzyme that helps protect cells by reducing peroxides using glutathione. In this study, researchers found that PRDX6 is overexpressed in multiple myeloma (MM) patients and its high levels are linked to worse outcomes. The enzyme’s high expression was also associated with markers of disease severity, such as β2-microglobulin, lactate dehydrogenase, and the International Staging System stage of MM. 

When PRDX6 was removed from MM cell lines, the cells experienced significant apoptosis (cell death). This happened because without PRDX6, levels of reactive oxygen species (ROS) increased, causing oxidative stress. This stress activated certain signaling pathways (like MAPK), leading to changes in proteins that regulate cell death, such as BAX and Bcl2, and triggering the activation of caspase 3. In addition, the lack of PRDX6 disrupted the cells’ mitochondria, causing structural damage and dysfunction.

Interestingly, when PRDX6 was deficient, MM cells responded better to bortezomib, a treatment used for MM. In animal studies, the absence of PRDX6 also slowed tumor growth. These findings suggest that PRDX6 helps protect MM cells from oxidative damage and maintains mitochondrial function. Targeting PRDX6 could improve the effectiveness of treatments like bortezomib in fighting MM.

 

 

"Updated analysis of EMN02 demonstrated overall survival benefit to early ASCT for multiple myeloma"

Source

Garfall, A.L. Updated analysis of EMN02 demonstrated overall survival benefit to early ASCT for multiple myeloma. Blood Cancer J. 15, 1 (2025). https://doi.org/10.1038/s41408-024-01198-1  January 3, 2025. 

Overview

In a recent commentary in the Blood Cancer Journal, Pawlyn et al. discussed the use of progression-free survival (PFS) as a substitute for overall survival (OS) in multiple myeloma trials. They mentioned that while autologous stem cell transplantation (ASCT) shows consistent improvements in PFS, its impact on OS has been less clear. They referred to the EMN02 study, which showed a PFS benefit with ASCT but no significant difference in OS. However, a longer follow-up of the EMN02 study, published at the 2020 ASH Annual Meeting, demonstrated a significant OS benefit with early ASCT, showing a positive relationship between PFS and OS in these trials. This OS benefit is even more noteworthy given that a large percentage of patients in the study (63%) eventually received ASCT as part of later treatment. The results of EMN02 support the idea that ASCT can improve OS, reinforcing the link between PFS and OS in these types of treatments.

 

 

"Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial"

Source

Nadeem, O., Aranha, M.P., Redd, R. et al. Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial. Nat Commun 16, 358 (2025). https://doi.org/10.1038/s41467-024-55308-5 January 3, 2025. 

Overview

The I-PRISM phase II trial studied a combination of ixazomib, lenalidomide, and dexamethasone in 55 patients with high-risk smoldering multiple myeloma (HR-SMM) to see if early treatment could improve long-term outcomes. The study did not reach its primary goal of median progression-free survival (PFS), but the secondary goal of biochemical PFS was 48.6 months. Some patients showed disease progression after or at the same time as meeting SLiM-CRAB criteria, which indicates progression to active myeloma. Overall, 93% of patients responded to the treatment, with 31% achieving complete response (CR) and 45% reaching very good partial response (VGPR) or better. Patients who achieved CR were less likely to have disease progression or meet SLiM-CRAB. Additionally, minimal residual disease (MRD) negativity was linked to a much longer time without disease progression (100% at 5 years) compared to MRD-positive patients (40%). The study also explored how tumor characteristics like MHC class I expression and T cell activity influenced treatment outcomes.

 

 

"The Presence of Clonal Isotype Switch After Autologous Stem Cell Transplantation as a Prognostic Biomarker for Long-Term Survival in Patients With Multiple Myeloma"

Source

Hanwool Cho, Jinhang Kim, Youngrok Park, Bo-Hee Lee, Misuk Yang, Yeongsic Kim, Jeong-A Kim, The Presence of Clonal Isotype Switch After Autologous Stem Cell Transplantation as a Prognostic Biomarker for Long-Term Survival in Patients With Multiple Myeloma, Leukemia Research, 2025, 107641, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2025.107641.  January 3, 2025. 

Overview

A study examined the role of clonal isotype switch (CIS) in multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT). CIS is when new types of immunoglobulins appear after treatment, often reflecting recovery of the immune system after high-dose chemotherapy and ASCT. The study found that 31.7% of patients developed CIS after treatment. Patients who received bortezomib-based therapy were more likely to experience CIS than those who had vincristine-doxorubicin-dexamethasone chemotherapy. Importantly, patients with CIS had significantly better overall survival and progression-free survival compared to those without CIS. The findings suggest that CIS could be a positive marker for better outcomes in MM patients after ASCT.

 

 

"Time to progression predicts outcome of patients with multiple myeloma that can be influenced by autologous hematopoietic stem cell transplantation"

Source

Yue, Y., Miao, Y., Zhou, Y., Shen, Y., Lu, L., Wang, F., … Gu, W. (2025). Time to progression predicts outcome of patients with multiple myeloma that can be influenced by autologous hematopoietic stem cell transplantation. Hematology, 30(1). https://doi.org/10.1080/16078454.2024.2448024  January 3, 2025

Overview

A recent study explored how the time to progression (TTP) after the first remission in multiple myeloma (MM) impacts overall survival (OS). Researchers analyzed data from 209 MM patients, dividing them into groups based on how long it took for their disease to progress after remission: ≤ 6 months, ≤ 12 months, ≤ 24 months, and > 24 months. The study found that patients whose disease progressed within 12 months of remission had a significantly shorter overall survival compared to those with longer periods of remission. For example, patients in the ≤ 6 months group had the shortest survival, with a median OS of just 33.63 months, while those in the 12–24 months group lived much longer, with a median OS of 100.43 months.

The research also showed that patients who had disease progression within 12 or 24 months after remission and underwent autologous hematopoietic stem cell transplantation (ASCT) after progression had better survival outcomes compared to those who only received chemotherapy. The study confirmed that TTP is an independent predictor for OS in MM, meaning that the sooner the disease recurs after remission, the worse the patient’s long-term outlook. This highlights the importance of monitoring TTP closely and suggests that ASCT could be a beneficial treatment for patients whose disease recurs earlier.

 

 

"Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma"

Source

Yu, H., Wu, C., He, J. et al. Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-024-06163-3  January 4, 2025. 

Overview

Multiple myeloma (MM) remains an incurable disease with high rates of relapse and resistance to chemotherapy. Researchers used a method called weighted gene co-expression network analysis (WGCNA) to compare gene expression between newly diagnosed MM and secondary plasma cell leukemia (sPCL). They identified 1,310 differentially expressed genes (DEGs) and focused on one key gene, PSMA4, which is linked to oxidative phosphorylation, a process in cells that helps produce energy. They found that high levels of PSMA4 were associated with drug resistance in myeloma, specifically to bortezomib, a chemotherapy drug.

Further experiments showed that myeloma cells resistant to bortezomib had increased PSMA4 expression, higher oxidative phosphorylation activity, and increased levels of reactive oxygen species (ROS). When researchers lowered PSMA4 levels, the cells became more sensitive to bortezomib again, suggesting that PSMA4 plays a key role in resistance. PSMA4 also triggered a hypoxia (low oxygen) state in the cells, which activated a signaling pathway (HIF-1α) that helped the cells survive chemotherapy. These findings suggest that PSMA4 contributes to myeloma resistance by boosting oxidative phosphorylation and promoting survival pathways, making it a potential target for improving treatment outcomes.

 

 

"The diagnostic and therapeutic potential of multiple myeloma-associated circular RNAs"

Source

Yue Zhao, Shaokun Wang, Shuang Fu, Xinxin Wang, Jihong Zhang, Fang Chen, The diagnostic and therapeutic potential of multiple myeloma-associated circular RNAs, Experimental Hematology,2025,104709,ISSN 0301-472X, https://doi.org/10.1016/j.exphem.2024.104709. January 3, 2025. 

Overview

Circular RNAs (circRNAs) were first discovered in viruses in 1974. They are formed through a process called back-splicing, where parts of RNA are connected to form a closed loop. Normally, circRNAs are stable, but in diseases like multiple myeloma (MM), they can play important roles in the development of the disease. CircRNAs can work in various ways, such as acting as "sponges" that regulate other RNA molecules, affecting gene expression, influencing protein production, and even producing small peptides.

In recent years, researchers have become more interested in how circRNAs contribute to MM, as they are involved in both the development and progression of the disease. Studies have shown that circRNAs could serve as useful markers to predict the prognosis of MM and might even be targets for new treatments. This review summarizes the structure of circRNAs, their role in MM, and the latest findings on how they influence the disease.

 

 

"Navigating the Economic Burden of Multiple Myeloma: Insights into Cost-effectiveness of CAR-T and Bispecific Antibody Therapies"

Source

Keesari, P.R., Samuels, D., Vegivinti, C.T.R. et al. Navigating the Economic Burden of Multiple Myeloma: Insights into Cost-effectiveness of CAR-T and Bispecific Antibody Therapies. Curr Hematol Malig Rep 20, 3 (2025). https://doi.org/10.1007/s11899-024-00748-5  January 4, 2025. 

Overview

Multiple myeloma (MM) has evolving treatment options. As new therapies like CAR-T and bispecific antibodies are approved, understanding their costs is important for both clinicians and healthcare systems. This review discusses the cost-effectiveness of these treatments compared to current therapies. It highlights that CAR-T therapy, especially when used early in treatment, may be more cost-effective depending on the region and model used. However, the cost-effectiveness of CAR-T varies based on factors like survival data, treatment-free remission periods, and the type of therapy used. Additional research is needed to explore these therapies’ costs in the long term, including potential indirect costs such as transportation and delays.

The review also examines bispecific antibodies, a newer treatment for MM, which show promising results in early trials, especially for patients resistant to other treatments. While these therapies may be less toxic than CAR-T, they are given over multiple sessions, potentially increasing the overall cost. The review notes that although bispecific antibody therapy shows better efficacy, more research is needed to assess its cost-effectiveness, particularly with long-term data. Overall, early use of effective therapies like CAR-T may reduce long-term costs, but further studies are essential to better understand the economics of both CAR-T and bispecific antibody treatments in MM.

 

 

"The prognostic impact of 1q21 gain/amplification in newly diagnosed multiple myeloma: a retrospective study based on a single center in China"

Source

Li, Y., Deng, J. & Chen, W. The prognostic impact of 1q21 gain/amplification in newly diagnosed multiple myeloma: a retrospective study based on a single center in China. Ann Hematol (2025). https://doi.org/10.1007/s00277-024-06164-2  January 4, 2025. 

Overview

In this study, researchers analyzed the impact of 1q21 gain/amp (a genetic abnormality) on the prognosis of 375 newly diagnosed multiple myeloma (MM) patients. They found that 1q21 gain/amp was present in nearly 44% of the patients, with some having 3 copies and others having 4 or more copies of the gene. Patients with this abnormality were more likely to have other complications like anemia, high calcium levels, and certain genetic changes (t(4;14) and t(14;16)). Those with 1q21 gain/amp had shorter progression-free survival (PFS) and overall survival (OS) compared to patients without the abnormality.

The study also found that patients with 1q21 amplification (more copies of the gene) had even worse survival outcomes than those with just 1q21 gain. However, patients who received autologous stem cell transplantation (ASCT) showed improved survival. The researchers developed a risk-scoring system that categorizes patients based on factors like 1q21 gain/amp, other high-risk genetic changes, and blood markers. This system could help doctors predict a patient’s prognosis and guide treatment decisions. Overall, the study highlights that 1q21 gain/amp, especially when combined with other high-risk factors, is linked to a worse prognosis in multiple myeloma.

 

 

"Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma"

Source

Wang, JX., Zhang, L., Zhang, PW. et al. Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma. Biol Direct 20, 1 (2025). https://doi.org/10.1186/s13062-024-00590-y  January 6, 2025. 

Overview

Despite advances in multiple myeloma (MM) treatment, many patients develop resistance to bortezomib (BTZ), a commonly used drug. This study looked into boanmycin, a new antibiotic, as a potential solution to overcome BTZ resistance in MM. Researchers created BTZ-resistant cell lines and tested the effects of boanmycin on these cells. The results showed that boanmycin effectively stopped the growth of both BTZ-sensitive and resistant MM cells. It also triggered cell death (apoptosis) and reduced the ability of cells to form colonies. When combined with BTZ, boanmycin worked even better than either drug alone.

In animal experiments, boanmycin slowed MM cell growth in mice without causing significant side effects. It was also able to kill patient-derived MM cells in lab tests. The study found that boanmycin works by damaging DNA, disrupting the cell cycle, and impairing the endoplasmic reticulum (ER), an essential part of the cell. These actions contribute to its effectiveness as an anti-cancer treatment. The findings suggest that boanmycin could be a promising treatment for MM, especially for patients who are resistant to BTZ.

 

 

"Design, synthesis and biological evaluation of bisnoralcohol derivatives as novel IRF4 inhibitors for the treatment of multiple myeloma"

Source

Jing-Zan Zhang, Lin Zhang, Xin Ding, Min Wu, De-Jie Zhang, Yujie Wu, Mingyao Liu, Chen-Chen Li, Zhengfang Yi, Wen-Wei Qiu, Design, synthesis and biological evaluation of bisnoralcohol derivatives as novel IRF4 inhibitors for the treatment of multiple myeloma, European Journal of Medicinal Chemistry, 2025,117240,ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2025.117240. January 6, 2025.  

Overview

Interferon regulatory factor 4 (IRF4) is a protein that plays a key role in the development and survival of multiple myeloma (MM). Because IRF4 is overexpressed in MM, it is an important target for new treatments. However, no chemical compound has been found that can directly bind to and inhibit IRF4—until now. In this study, researchers discovered a new compound, SH514, that can block IRF4. SH514 was developed from a compound called bisnoralcohol (BA) derivative 18, which showed promise in early tests. When tested, SH514 was found to effectively inhibit IRF4 and stop the growth of MM cells, especially those with high levels of IRF4 expression.

SH514 works by binding to a specific part of IRF4 called the DNA-binding domain (DBD), preventing it from activating genes that help MM cells grow. These genes include those responsible for cell cycle progression and survival. In lab tests, SH514 was shown to reduce the levels of several important proteins linked to cell growth, including Cyclins and CMYC. When tested in mice, SH514 not only slowed the growth of MM tumors but also performed better than the current treatment, lenalidomide, without causing significant toxicity. These findings suggest that SH514 and other IRF4 inhibitors could be valuable in developing new treatments for MM.

 

 

"Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome: Kinetics of iP with CAR-T cell products"

Source

Kenta Hayashino, Wataru Kitamura, Nobuharu Fujii, Toshiki Terao, Hiroki Kobayashi, Chihiro Kamoi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Yoshinobu Maeda, Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome: Kinetics of iP with CAR-T cell products, Cytotherapy, 2025, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2024.12.014. January 6, 2025.  

Overview

Hypophosphatemia, or low levels of phosphate in the blood, has become a recognized side effect of chimeric antigen receptor (CAR) T-cell therapy, affecting about 70-75% of patients. This condition can lead to severe symptoms similar to cytokine release syndrome (CRS), such as problems with breathing and heart function. While some CAR-T treatments have shown a connection between phosphate levels and CRS, the relationship between phosphate and another CAR-T therapy called idecabtagene vicleucel (ide-cel) has not been studied until now. This research aimed to compare how phosphate levels change over time after different CAR-T treatments and explore how hypophosphatemia relates to severe CRS.

The study looked at 108 patients who received various CAR-T therapies, including ide-cel, and measured their phosphate levels over 21 days. Results showed that patients treated with ide-cel had significantly higher rates of hypophosphatemia, with 92.3% experiencing low phosphate levels, compared to 67.5% in patients receiving other CAR-T therapies. In addition, ide-cel patients had lower phosphate levels for longer periods. While previous research showed a clear link between severe CRS and hypophosphatemia in patients treated with other CAR-T therapies, this was not observed with ide-cel, where the phosphate levels were equally low in both mild and severe CRS cases. The study suggests that careful monitoring of phosphate levels is especially important for patients receiving ide-cel, as they are more likely to experience severe hypophosphatemia.

 

 

"Analysis of early efficacy and immune reconstitution after autologous hematopoietic stem cell transplantation in multiple myeloma"

Source

Chen, K., Liang, H., Yu, Z. et al. Analysis of early efficacy and immune reconstitution after autologous hematopoietic stem cell transplantation in multiple myeloma. Sci Rep 15, 1222 (2025). https://doi.org/10.1038/s41598-024-84047-2  January 7, 2025. 

Overview

This study looked at how autologous hematopoietic stem cell transplantation (auto-HSCT) can benefit patients with primary multiple myeloma (MM). The research included 94 MM patients who underwent auto-HSCT and tracked various factors, including treatment effectiveness, immune system recovery, and the time it took for blood cell production to return to normal. After the transplant, patients showed significant improvement, with many achieving a very good partial response (VGPR) or complete response (CR) compared to before the transplant.

The study also analyzed how the immune system recovered after the transplant. It found that certain immune cells, like B-cells and T-cells, decreased before the transplant but then significantly increased afterward, which helped restore the immune system. Interestingly, patients in higher-risk groups still experienced better outcomes after the transplant, with auto-HSCT helping to overcome some of the challenges these patients face. Overall, auto-HSCT not only improved remission rates but also helped rebuild the immune system, making it an effective treatment for MM.

 

 

"Disease characteristics and treatment outcomes of Myeloma patients under 50 years of age: an analysis of the Balkan Myeloma Study Group"

Source

Despina Fotiou, Sorina Nicoleta Badelita, Eirini Katodritou, Meral Beksac, Jelena Bila, Emmanouil Spanoudakis, Josip Batinić, Daniel Coriu, Sinziana Barbu, Catalin Danaila, Dimitra Dalampira, Angeliki Sevastoudi, Guldane Cengiz Seval, Selami Koçak Toprak, Aleksandra Sretenovic, Olivera Markovic, Toni Valkovic, Zorica Cvetkovic, Fenia Theodorakakou, Maria Gavriatopoulou, Evangelos Terpos, Meletios A. Dimopoulos, Efstathios Kastritis, Disease characteristics and treatment outcomes of Myeloma patients under 50 years of age: an analysis of the Balkan Myeloma Study Group, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2024.12.017.  January 7, 2025. 

Overview

This study focused on younger multiple myeloma (MM) patients, who make up about 10% of all cases. Researchers looked at data from 350 patients under 50 years old to understand their disease characteristics, treatment outcomes, and factors affecting their survival. Younger patients typically had fewer issues with kidney problems and anemia but were more likely to have bone damage and unfavorable genetic changes. When it came to treatment, younger patients had better responses and longer survival rates compared to older patients. The 5-year and 10-year survival rates were 76% and 64%, with a median survival of more than 15 years.

The study also found that factors like anemia, high calcium levels, and poor genetics were linked to worse survival. Autologous stem cell transplantation (ASCT) played a significant role in improving survival and progression-free survival. These findings suggest that younger MM patients have unique disease features and respond well to aggressive treatment, emphasizing the need for personalized treatment plans to potentially cure the disease.

 

 

"Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients"

Source

E.A. Martino, S. Palmieri, M. Galli, D. Derudas, R. Mina, R. Della Pepa, R. Zambello, E. Vigna, A. Bruzzese, S. Mangiacavalli, E. Zamagni, C. Califano, M. Musso, C. Conticello, C. Cerchione, G. Mele, N. Di Renzo, M. Offidani, G. Tarantini, G.M. Casaluci, A. Rago, R. Ria, G. Uccello, G. Barilà, G. Palumbo, L. Pettine, C. De Magistris, I.D. Vincelli, M. Brunori, F. Accardi, V. Amico, A. Amendola, R. Fontana, V. Bongarzoni, B. Rossini, E. Cotzia, A. Gozzetti, R. Rizzi, N. Sgherza, P. Curci, K. Mancuso, G. Reddiconto, A. Maroccia, L. Franceschini, G. Bertuglia, D. Nappi, E. Barbieri, M. Quaresima, M.T. Petrucci, F. Di Raimondo, A. Neri, G. Tripepi, P. Musto, F. Morabito, M. Gentile, Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients,ESMO Open, Volume 10, Issue 2, 2025,104084, ISSN 2059-7029, https://doi.org/10.1016/j.esmoop.2024.104084. January 7, 2025. 

Overview

This study looked at the treatment effectiveness of elotuzumab, pomalidomide, and dexamethasone (EloPd) in patients with daratumumab-refractory multiple myeloma (Dara-R MM), a condition where the disease doesn't respond to previous treatments. The study included 247 patients who were also resistant to other drugs like lenalidomide and proteasome inhibitors. 

The results showed that EloPd led to an overall response rate of 52.6%. Patients had a median progression-free survival (PFS) of 6.6 months and an overall survival (OS) of 17.0 months. Factors like advanced disease stage, low hemoglobin levels, relapse symptoms, and prior treatments with daratumumab were linked to shorter survival. Interestingly, there was no significant difference in PFS or OS between patients who were resistant to all three drug classes (triple-class refractory) and those who were not.

The study also created two risk scores to predict patient outcomes based on their characteristics. EloPd was found to be an effective treatment for Dara-R MM, offering good disease control and potentially helping patients until they can receive newer treatments like CAR-T therapy or bispecific antibodies.

 

 

"Network analysis of cross-income-level collaboration on multiple myeloma in sub-Saharan Africa"

Source

Yang, K., Benkwitz-Bedford, S., Cazier, JB. et al. Network analysis of cross-income-level collaboration on multiple myeloma in sub-Saharan Africa. npj Health Syst. 2, 1 (2025). https://doi.org/10.1038/s44401-024-00003-2  January 7, 2025. 

Overview

Collaboration between high-income and low- and middle-income countries (LMICs) is important for improving global health, especially for diseases like multiple myeloma (MM), which is not well-researched in sub-Saharan Africa (SSA). This study looked at research on MM published between 2002 and 2022, using a tool to analyze how institutions collaborate. The findings showed that most MM research in SSA is done within high-income countries (HICs) and with a few institutions in South Africa and Nigeria. To improve MM research in SSA, more collaboration between countries of different income levels is needed. The analysis tool highlights gaps in research and helps identify leading institutions to promote better international partnerships and strategies.

 

 

"Diagnostik beim multiplen Myelom. (Diagnosis of Multiple Myeloma)"

Source

John, L., Weinhold, N. & Raab, MS. Diagnostik beim multiplen Myelom. (Diagnosis of Multiple Myeloma) Onkologie (2025). https://doi.org/10.1007/s00761-024-01652-6  January 8, 2025. 

Overview

Early detection of multiple myeloma (MM) is key to preventing long-term damage of the disease. To diagnose it, doctors need a thorough medical history, physical exam, lab tests, a bone marrow sample, and imaging of the bones. The medical history and exam help detect signs of serious issues like fractures or nerve damage. Kidney problems should also be checked right away. Lab tests that detect abnormal proteins are essential for confirming the diagnosis, while tests for calcium levels and kidney function show how urgently treatment is needed. Imaging like CT scans can find bone damage, and MRI or PET scans help determine if the disease requires treatment. A bone marrow biopsy confirms the diagnosis, and advanced techniques like genetic testing and next-generation sequencing (NGS) help assess the disease and guide treatment. Close teamwork between different medical specialists is crucial for providing the best care.

 

 

"Evolution of frontline treatment for multiple myeloma: clinical investigation of quadruplets containing carfilzomib and anti-CD38 monoclonal antibodies"

Source

Costa, L.J., Gay, F., Landgren, O. et al. Evolution of frontline treatment for multiple myeloma: clinical investigation of quadruplets containing carfilzomib and anti-CD38 monoclonal antibodies. Ann Hematol (2025). https://doi.org/10.1007/s00277-024-06143-7  January 8, 2025. 

Overview

Achieving deep remissions in multiple myeloma (MM), especially by reducing minimal residual disease (MRD), is crucial for improving survival. The standard treatment for newly diagnosed multiple myeloma (NDMM) involves a combination of three therapies (a triplet regimen), with or without a stem cell transplant, or two therapies (a doublet regimen) for patients who cannot tolerate more intensive treatments.

Recently, monoclonal antibodies (mAbs) like daratumumab (Dara) or isatuximab (Isa) have been added to frontline treatments. Clinical trials are testing the combination of these mAbs with other drugs, such as carfilzomib, lenalidomide, and dexamethasone (KRd). This quadruple therapy (Isa/Dara-KRd) has shown promising results, with high rates of deep responses and MRD negativity, meaning little to no trace of the disease. The treatment works well across various patient groups, including those of different ages, those eligible for transplants, and those with different genetic risks. Importantly, the therapy does not seem to cause unexpected or serious safety problems. These findings suggest that more personalized treatments based on risk and response may be possible for people with NDMM.

 

 

"The Role of Lifestyle and Environmental Factors in the Pathogenesis of Multiple Myeloma"

Source

Suska, A., Tyczyńska, A., Zaucha, J.M., Kopińska, A., Helbig, G., Markiewicz, M., Warzybok, K., Leder, E., Grosicki, S., Machaliński, B., Baumert, B., Bator, M., Usnarska-Zubkiewicz, L., Fornagiel, S., Ciepłuch, H., Waszczuk-Gajda, A., Kruczkowska-Tarantowicz, K., Rzepecki, P., Hus, M., Morawska-Krekora, A., Raźny, M., Charliński, G., Puła, A., Nita, E., Wojciechowska, M., Krawczyk-Kuliś, M., Goldberg, J., Woźny, T., Rodzaj, M., Olejarz, D., Gronau-Dziurkowska, M., Skalniak, E., Krzysztoń, J., Niezabitowska, K. and Jurczyszyn, A. (2025), The Role of Lifestyle and Environmental Factors in the Pathogenesis of Multiple Myeloma. Eur J Haematol. https://doi.org/10.1111/ejh.14356  January 8, 2025. 

Overview

A study in Poland looked at how lifestyle and environmental factors may influence the development of multiple myeloma (MM). Researchers surveyed 274 patients newly diagnosed with MM and 208 healthy individuals to understand the role of factors like exercise, exposure to harmful substances, and sociodemographic data.

The results showed that regular physical activity, such as sports practiced for at least six months, helped protect against MM. On the other hand, certain environmental exposures increased the risk of developing the disease, including pesticides, asphalt, coal dust, organic vapors, metal dust, exhaust fumes, and chemicals.

The study suggests that while the causes of MM are complex, lifestyle choices, particularly physical activity, and environmental exposures can influence the risk of developing the disease.

 

 

"Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial"

Source

Richardson, P., Beksaç, M., Oriol, A., Lindsay, J., Schjesvold, F., Galli, M., Yağcı, M., Larocca, A., Weisel, K., Yu, X., Donahue, C., Acosta, J., Peluso, T. and Dimopoulos, M. (2025), Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial. Eur J Haematol. https://doi.org/10.1111/ejh.14365  January 8, 2025.  

Overview

The OPTIMISMM trial looked at the effectiveness of two treatments for relapsed and refractory multiple myeloma (RRMM): pomalidomide/bortezomib/dexamethasone (PVd) and bortezomib/dexamethasone (Vd). The study found that PVd significantly improved progression-free survival (PFS) compared to Vd. Now, the final results for overall survival (OS) and updated treatment effectiveness have been reported.

The trial involved adults with RRMM who had already received 1–3 prior treatments. After an average follow-up of about 64.5 months, the median OS was 35.6 months with PVd compared to 31.6 months with Vd. Although the difference in OS was not statistically significant, adjusting for additional therapies showed a significant improvement with PVd. The median second progression-free survival (PFS2) was also better with PVd (22.1 months) compared to Vd (16.9 months).

In terms of side effects, more patients in the PVd group had to stop treatment due to adverse events (33.1%) compared to the Vd group (19.6%).

The study suggests that while PVd did not significantly extend overall survival, it did offer better results in terms of PFS2, supporting its use in treating RRMM.

 

 

"RedirecTT-1 Investigators and Study Group. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma"

Source

Yael C. Cohen, M.D., Hila Magen, M.D., Moshe Gatt, M.D., Michael Sebag, M.D., Ph.D., Kihyun Kim, M.D., Chang-Ki Min, M.D., Enrique M. Ocio, M.D., Ph.D., Sung-Soo Yoon, M.D., Ph.D., Michael P. Chu, M.D., Paula Rodríguez-Otero, M.D., Ph.D., Irit Avivi, M.D., Natalia A. Quijano Cardé, Ph.D., Ashwini Kumar, Ph.D., Maria Krevvata, Ph.D., Michelle R. Peterson, M.Sc., Lilla Di Scala, Ph.D., Emma Scott, M.D., Brandi Hilder, Ph.D., Jill Vanak, Ph.D., Arnob Banerjee, M.D., Ph.D., Albert Oriol, M.D., Ph.D., Daniel Morillo, M.D., and María-Victoria Mateos, M.D., Ph.D., for the RedirecTT-1 Investigators and Study Group. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med 2025;392:138-149 DOI: 10.1056/NEJMoa2406536 VOL. 392 NO. 2 January 8, 2025.  

Overview

A study tested the combination of two bispecific antibodies, talquetamab and teclistamab, to treat patients with relapsed or refractory multiple myeloma. Both of these antibodies work by activating T cells to target cancer cells. This phase 1b–2 study aimed to evaluate the safety and effectiveness of this combination.

The study included 94 patients, with 44 receiving the recommended treatment dose: talquetamab (0.8 mg/kg) and teclistamab (3.0 mg/kg) every other week. The most common side effects were cytokine release syndrome, neutropenia (low white blood cell count), taste changes, and skin issues. Serious side effects, including infections and blood cell problems, occurred in most patients, with 64% experiencing severe infections.

Despite the side effects, the treatment showed promising results. About 80% of patients treated with the recommended regimen had a response, and 86% of them were still responding after 18 months. Even among patients with extramedullary disease (cancer outside the bone marrow), 82% of them continued responding at 18 months.

The combination of talquetamab and teclistamab was effective, but it had a higher risk of severe infections compared to using either treatment alone. The results suggest the combination could offer durable responses for patients with advanced multiple myeloma.

 

 

"Tunneling nanotubes between bone marrow stromal cells support transmitophagy and resistance to apoptosis in myeloma"

Source

Solimando, A.G., Di Palma, F., Desantis, V. et al. Tunneling nanotubes between bone marrow stromal cells support transmitophagy and resistance to apoptosis in myeloma. Blood Cancer J. 15, 3 (2025). https://doi.org/10.1038/s41408-025-01210-2  January 9, 2025.   

Overview

Multiple myeloma (MM) thrives in the bone marrow, where low oxygen and glucose levels force cancer cells to change how they generate energy. This change, known as the Warburg effect, makes MM cells rely more on a process called glycolysis, which creates an acidic environment that helps the cancer grow. Understanding how MM cells survive and grow in this challenging environment could lead to new treatments.

In this study, researchers explored how MM cells survive in low-oxygen and glucose-starved conditions, similar to what they experience in the bone marrow. They discovered a new mechanism that helps MM cells stay alive: the transfer of damaged mitochondria (the energy-producing parts of cells) from MM cells to bone marrow stromal cells (BMSCs). This process, called "transmitophagy," helps MM cells survive in the harsh microenvironment by sending damaged mitochondria to BMSCs, where they are broken down. 

A key part of this process involves structures called tunneling nanotubes (TNTs), which are tiny connections between cells. These TNTs allow the transfer of mitochondria between BMSCs and MM cells, providing support for MM cells to survive. When TNTs were destroyed, BMSCs could no longer protect MM cells, highlighting how important TNTs are for MM survival.

The study also found that in these low-oxygen conditions, the mitochondria transferred from MM cells were in a "post-fission" state, meaning they had already split into smaller parts. This suggests that MM cells use transmitophagy to maintain their energy production by sharing and recycling mitochondria with BMSCs.

The findings point to the potential of targeting the TNTs and mitochondrial transfer process as a new way to treat MM. By disrupting this protective mechanism, it may be possible to weaken the support BMSCs provide to MM cells, offering a new approach to fighting the disease.

 

 

"Characterizing sexuality and assessing predictors of sexual satisfaction in patients with multiple myeloma and other hematological cancers"

Source

Henkelman, M.S., Toivonen, K.I., Tay, J. et al. Characterizing sexuality and assessing predictors of sexual satisfaction in patients with multiple myeloma and other hematological cancers. Support Care Cancer 33, 85 (2025). https://doi.org/10.1007/s00520-024-09038-5  January 9, 2025.    

Overview

The OPTIMISMM trial compared two treatment combinations for patients with relapsed or refractory multiple myeloma (RRMM) who had been previously treated with lenalidomide. One group received a combination of pomalidomide, bortezomib, and dexamethasone (PVd), while the other received bortezomib and dexamethasone (Vd). The study focused on how long patients stayed without their disease getting worse (progression-free survival, PFS) and overall survival (OS).

The results showed that PVd improved median PFS2 (the time patients stayed free from disease progression after their first line of treatment) compared to Vd. However, when looking at overall survival (OS), the difference between PVd and Vd wasn't significant. OS was 35.6 months with PVd and 31.6 months with Vd, with PVd showing some improvement after adjusting for other treatments patients received later on.

While treatment-related side effects caused more people in the PVd group to stop treatment (33%) compared to the Vd group (20%), the overall findings suggest that PVd might still offer benefits, especially in delaying disease progression in RRMM patients.

 

 

"T cell malignancies after CAR T cell therapy in the DESCAR-T registry"

Source

Dulery, R., Guiraud, V., Choquet, S. et al. T cell malignancies after CAR T cell therapy in the DESCAR-T registry. Nat Med (2025). https://doi.org/10.1038/s41591-024-03458-w  January 8, 2025. 

Overview

Chimeric antigen receptor (CAR) T-cell therapy is a treatment for certain types of cancer, but there has been concern about the potential risk of developing T-cell malignancies after receiving this therapy. In a study analyzing data from 3,066 patients in France who received CAR T-cell therapy for hematologic cancers, only one patient (0.03%) developed a T-cell malignancy. This patient, diagnosed with a rare T-cell lymphoma three years after receiving tisagenlecleucel therapy for lymphoma, had the CAR T-cell therapy integrated into a tumor suppressor gene.

Overall, the study found that the risk of developing a T-cell malignancy after CAR T-cell therapy is very low, providing reassurance about the safety of this treatment.

 

 

"Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy"

Source

David G. Coffey, Pinar Ataca Atilla, Erden Atilla, Ola Landgren, Andrew J. Cowan, Sylvain Simon, Margot J. Pont, Melissa L. Comstock, Geoffrey R. Hill, Stanley R. Riddell, Damian J. Green; Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy. Blood 2025; 145 (2): 220–233. doi: https://doi.org/10.1182/blood.2024025231  January 9, 2025. 

Overview

Chimeric antigen receptor (CAR) T-cell therapy is a treatment for certain types of cancer, but there has been concern about the potential risk of developing T-cell malignancies after receiving this therapy. In a study analyzing data from 3,066 patients in France who received CAR T-cell therapy for hematologic cancers, only one patient (0.03%) developed a T-cell malignancy. This patient, diagnosed with a rare T-cell lymphoma three years after receiving tisagenlecleucel therapy for lymphoma, had the CAR T-cell therapy integrated into a tumor suppressor gene.

The study found that the risk of developing a T-cell malignancy after CAR T-cell therapy is very low, providing reassurance about the safety of this treatment.

 

 

"Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy"

Source

Maximilian Merz, Nico Gagelmann; GSI: myeloma—cold case closed?. Blood 2025; 145 (2): 148–149. doi: https://doi.org/10.1182/blood.2024027056  January 9, 2025. 

Overview

A new study by Coffey et. al explores how inhibiting γ-secretase (GSI) can help overcome resistance to BCMA-targeted therapies in multiple myeloma (MM) patients, particularly those without genetic changes to BCMA. BCMA-targeted therapies, such as CAR T-cell therapy, have improved outcomes for patients with relapsed or refractory MM, but some patients develop resistance, especially those who don't have genetic changes in BCMA. The study focuses on the role of γ-secretase, which can lower BCMA on the surface of plasma cells, possibly contributing to this resistance.

In the study, the GSI drug crenigacestat was given to patients before and after CAR T-cell therapy. The results showed that crenigacestat helped increase BCMA levels on plasma cells and decreased soluble BCMA in the blood, which is associated with better treatment responses. The treatment also altered the bone marrow environment by affecting certain immune cells, particularly nonclassical monocytes.

One key finding was that GSI reduced soluble BCMA in the blood quickly, within hours of treatment, which may help overcome resistance to BCMA-targeted therapies. The study suggests that combining GSI with CAR T-cell therapy could improve treatment outcomes for MM patients, particularly those with high levels of soluble BCMA.

This research demonstrates the potential of GSI to boost the effectiveness of BCMA-targeted therapies by preventing resistance mechanisms and altering the tumor environment in ways that support immune cell function. 

 

 

"Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma"

Source

Jan Eckmann, Tanja Fauti, Marlene Biehl, Aintzane Zabaleta, Laura Blanco, Iva Lelios, Stefan Gottwald, Richard Rae, Stefanie Lechner, Christa Bayer, Quincy Dekempe, Franz Osl, Nadege Carrié, Sahar Kassem, Stefan Lorenz, Tony Christopeit, Alejandro Carpy, Alexander Bujotzek, Ann-Marie Bröske, Iryna Dekhtiarenko, Jan Attig, Leo Kunz, Floriana Cremasco, Roberto Adelfio, Georg Fertig, Stefan Dengl, Christian Gassner, Felix Bormann, Claudia Kirstenpfad, Thomas Kraft, Sarah Diggelmann, Melanie Knobloch, Carina Hage, Romi Feddersen, Gordon Heidkamp, Thomas Pöschinger, Maud Mayoux, Luise Bernasconi, Felipe Prosper, Charles Dumontet, Ludovic Martinet, Stéphane Leclair, Wei Xu, Bruno Paiva, Christian Klein, Pablo Umaña; Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma. Blood 2025; 145 (2): 202–219. doi: https://doi.org/10.1182/blood.2024025987  January 9, 2025. 

Overview

New treatments for multiple myeloma (MM) like "off-the-shelf" T-cell bispecific antibodies (TCBs) targeting BCMA and GPRC5D have shown promise. Yet, issues like resistance, short-lasting responses, and tumor relapses still occur. GPRC5D is a promising target for MM, but recent research shows that tumors may lose this target more frequently than BCMA, making it crucial for therapies to act quickly.

Forimtamig is a new GPRC5D-targeting TCB that binds more strongly to GPRC5D compared to other TCB formats. This stronger binding leads to better tumor cell killing and activation of T-cells. In mouse models, forimtamig successfully recruited immune cells to the bone marrow and quickly killed tumors, even when higher doses were used to reduce side effects like cytokine release. Combining forimtamig with standard MM treatments, such as anti-CD38 antibodies and immunomodulatory drugs, enhanced its effectiveness. It also worked well with newer therapies, like BCMA TCB and cereblon E3 ligase modulatory drugs, helping prevent the tumor from becoming resistant.

Forimtamig is currently being tested in Phase 1 clinical trials for patients with relapsed and refractory MM, both on its own and in combination with other treatments. The trial is registered under ClinicalTrials.gov #NCT04557150.

 

 

"Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials"

Source

Ntanasis-Stathopoulos, I., Filippatos, C., Ntanasis-Stathopoulos, A., Malandrakis, P., Kastritis, E., Tsitsilonis, O.E., Dimopoulos, M.A., Terpos, E. and Gavriatopoulou, M. (2025), Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials. Am J Hematol. https://doi.org/10.1002/ajh.27582  January 9, 2025.  

Overview

This meta-analysis reviewed the relationship between minimal residual disease (MRD) negativity and survival outcomes in 15,304 multiple myeloma (MM) patients from randomized trials published until June 2024. The results showed a strong link between MRD negativity and better survival outcomes. Specifically, MRD negativity was significantly associated with improved progression-free survival (PFS) and overall survival (OS). This connection was especially strong in newly diagnosed patients, where MRD negativity was linked to better PFS. For patients with relapsed or refractory MM, the relationship was less clear. The analysis also found that maintaining MRD negativity for a year was strongly connected to longer PFS. This study supports the idea that MRD negativity is a reliable marker for survival in MM.

 

 

"Multiple myeloma–associated non-crystalline proximal tubulopathy and crystalline cast nephropathy: Biochemical and structural features of disease-causing monoclonal kappa light chains"

Source

Ezawa T, Otomo R, Kariya Y, et al. Multiple myeloma–associated non-crystalline proximal tubulopathy and crystalline cast nephropathy: Biochemical and structural features of disease-causing monoclonal kappa light chains. The FASEB Journal. 2025; 39:e70296. doi:10.1096/fj.202402104R  January 9, 2025. 

Overview

This study explores a rare case of two kidney diseases caused by monoclonal immunoglobulin light chains (LCs) in a patient with multiple myeloma (MM). These diseases are non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN). The patient’s urine showed the presence of κ-LCs (also known as Bence-Jones proteins), which were confirmed through immunofixation. A kidney biopsy revealed damage to the tubular cells, with vacuoles in the proximal cells and casts in the distal tubes. Further tests showed specific proteins in the cells, and electron microscopy revealed vacuolation and an increase in lysosomes. The distal casts had numerous crystals in different shapes. To better understand the cause of the kidney damage, the researchers performed various analyses on the κ-LC protein. They identified that the protein came from a specific gene (IGKV1-39) and had features like a positively charged surface, which could promote protein binding to kidney cells and form organized casts. This study provides new insights into the biochemical characteristics of the proteins that cause these MM-related kidney diseases.

 

 

"Krankheitsassoziierte, patientenbezogene und therapiebedingte Komplikationen beim multiplen Myelom"

Source

Rapi, A., Hampel, M., Mai, E.K. et al. Krankheitsassoziierte, patientenbezogene und therapiebedingte Komplikationen beim multiplen Myelom. Onkologie (2025). https://doi.org/10.1007/s00761-024-01659-z  January 10, 2025. 

Overview

Even though treatments have made multiple myeloma (MM) more manageable for most people, complications from the disease or its treatment continue to be significant challenges. The development of new therapies has increased the complexity of treatment, making it important to balance effectiveness with tolerability. Ongoing monitoring of patients is essential for detecting comorbidities and side effects early, which helps improve quality of life and prevent damage to organs. Before starting treatment, a thorough evaluation is necessary to determine the best treatment approach, especially considering whether a patient is "frail" or "fit." Long-term clinical data are needed to better understand and manage rare or late-onset side effects, like secondary cancers. The main goal is to improve outcomes for MM patients.

 

 

"Factors affecting pretransplant muscle strength in allogeneic stem cell transplant candidates prior transplantation"

Source

Limbach, M., Kuehl, R., Koeppel, M. et al. Factors affecting pretransplant muscle strength in allogeneic stem cell transplant candidates prior transplantation. Support Care Cancer 33, 89 (2025). https://doi.org/10.1007/s00520-024-09140-8  January 10, 2025. 

Overview

Physical performance plays an important role in predicting outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT). While cardiorespiratory fitness is already known to be a key factor, muscle strength, including conditions like sarcopenia, is increasingly recognized as clinically important. This study aimed to measure muscle strength and identify risk factors for reduced performance before transplantation.

Researchers assessed muscle strength in 212 patients (average age 54.5 years) just before they were admitted for allo-HCT. They measured knee extension and hip flexion strength and compared the results to healthy reference values. The study found significant reductions in muscle strength compared to these healthy benchmarks, particularly in younger patients and males. Factors like age, female gender, lower body mass index (BMI), and a higher comorbidity index (HCT-CI) were linked to weaker muscle strength.

The findings suggest that muscle strength is notably lower before allo-HCT and highlight the importance of targeting certain patient groups (such as younger, male, or lower BMI patients) for pre-transplant exercise or resistance training to better prepare them for the procedure.

 

 

"Evaluation of clinical characteristics and prognostic factors of early progressive disease (EPD) in newly diagnosed Multiple Myeloma patients: Real-world data of the Greek Myeloma Study Group"

Source

Eirini Katodritou, Efstathios Kastritis, Dimitra Dalampira, Despina Fotiou, Fotini Theodorakakou, Sosana Delimpasi, Emmanouil Spanoudakis, Ioannis Ntanasis-Stathopoulos, Theodosia Papadopoulou, Aggeliki Sevastoudi, Theodora Triantafyllou, Aikaterini Daiou, Anastasia Pouli, Magda Migkou, Maria Gavriatopoulou, Evgenia Verrou, Marie Christine Kyrtsonis, Meletios-Athanasios Dimopoulos, Evangelos Terpos, Evaluation of clinical characteristics and prognostic factors of early progressive disease (EPD) in newly diagnosed Multiple Myeloma patients: Real-world data of the Greek Myeloma Study Group, Clinical Lymphoma Myeloma and Leukemia,2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.01.002. January 10, 2025.  

Overview

Early progressive disease (EPD) is a significant challenge in newly diagnosed multiple myeloma (MM), affecting over 20% of patients. EPD is defined as disease progression or relapse within 18 months of initial treatment response. This study analyzed data from 1,436 patients, identifying key characteristics and treatment patterns linked to EPD. Patients with EPD were typically older and had more advanced disease, including higher levels of β2-microglobulin and LDH, lower hemoglobin, and impaired kidney function. They also more frequently presented with advanced staging (ISS3, RISS3, and R2-ISS stage III/IV) and ultra-high-risk MM (UHR-MM), characterized by multiple high-risk genetic abnormalities.  

Treatment outcomes in EPD patients were notably poorer. Only 12% achieved a complete response to induction therapy, compared to 27% of those without EPD. Access to key therapies also varied; fewer EPD patients received daratumumab-based treatments (2% vs. 10%) or underwent autologous stem cell transplant (ASCT) (11% vs. 33%). These disparities contributed to significantly shorter survival outcomes, with median progression-free survival (PFS) of 10 months and overall survival (OS) of 29 months, compared to 40 months and 76 months, respectively, for other patients.  

The study identified key predictors of EPD, including advanced R2-ISS stage, lack of daratumumab-based therapies, and absence of ASCT. These findings underscore the importance of personalized treatment approaches and broader access to effective therapies. The R2-ISS staging system could serve as a valuable tool for identifying high-risk patients, helping clinicians make informed decisions to potentially reduce the risk of EPD and improve long-term outcomes.

 

 

"Mechanisms for resistance to BCMA-targeted immunotherapies in multiple myeloma"

Source

Tingting Yue, Yue Sun, Yun Dai, Fengyan Jin, Mechanisms for resistance to BCMA-targeted immunotherapies in multiple myeloma, Blood Reviews, 2025, 101256, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2025.101256. January 11, 2025. 

Overview

BCMA-targeted immunotherapies, such as CAR T-cell therapy, bispecific T-cell engagers (TCEs), and antibody-drug conjugates (ADCs), have shown promise in treating relapsed or refractory multiple myeloma (RRMM). However, while these therapies are effective in the short term, their impact on long-term survival is still unclear, and resistance to treatment remains a significant challenge.  

Current research is focused on understanding and overcoming this resistance. Studies suggest that resistance may result from issues like antigen loss, T cell dysfunction, and factors in the immune tumor microenvironment. Despite these hurdles, researchers are exploring strategies to enhance the durability and effectiveness of BCMA-targeted therapies.  

This review highlights the latest findings on resistance mechanisms and offers insights into potential solutions, paving the way for improved outcomes in myeloma treatment.

 

 

"Risk of infections in bispecific antibody therapy for multiple myeloma: a comprehensive review of literature"

Source

Alshammari, F., Alrajhi, A. M., & Howaidi, J. (2025). Risk of infections in bispecific antibody therapy for multiple myeloma: a comprehensive review of literature. Hematology, 30(1). https://doi.org/10.1080/16078454.2024.2448898  January 10, 2025. 

Overview

Bispecific antibodies (BsAbs) have revolutionized multiple myeloma (MM) treatment by targeting antigens like BCMA, CD38, and FcRH5 with high precision. However, these therapies come with a notable risk of infections, a critical concern for MM patients.  

About 56% of patients on BsAbs experience infections, with severe (Grade 3/4) cases making up 24%. BCMA-targeted BsAbs carry the highest infection risk, linked to neutropenia, hypogammaglobulinemia, and factors related to the disease and individual patients. The most common infections are bacterial, affecting the respiratory and gastrointestinal tracts, followed by viral infections like CMV and rhinovirus. Fungal infections, while less frequent, are also reported.  

To reduce these risks, personalized prevention strategies are essential. All patients receiving BsAbs for relapsed/refractory MM should receive prophylaxis for viral infections, while bacterial and fungal prophylaxis depends on individual risk factors. These measures help balance the benefits of BsAb therapy with its potential complications.

 

 

"Identifying potential prognosis markers in relapsed multiple myeloma via integrated bioinformatics analysis and biological experiments"

Source

Yong Xu, Xinya Cao, He Zhou, Han Xu, Bing Chen, Hua Bai, Identifying potential prognosis markers in relapsed multiple myeloma via integrated bioinformatics analysis and biological experiments, Current Research in Translational Medicine, 2025, 103495, ISSN 2452-3186, https://doi.org/10.1016/j.retram.2025.103495. January 12, 2025. 

Overview

Relapsed multiple myeloma (MM) remains a major challenge, as most patients eventually experience disease progression despite current treatments. Traditional clinical parameters have proven unreliable for predicting relapse, prompting a shift toward molecular targets for better prognostic accuracy.  

Using bioinformatics and biological experiments, researchers identified four key genes—CENPE, ASPM, TOP2A, and FANCI—linked to MM relapse. These genes are involved in critical processes like cell division, mitosis, and DNA replication. A relapse gene score (RGS) model based on these genes was developed and successfully validated in two separate patient groups, offering a more precise tool to predict relapse risk and outcomes.  

Additionally, the study highlighted the therapeutic potential of targeting CENPE. The CENPE inhibitor GSK923295 demonstrated promising anti-myeloma effects, including inducing cell death, halting the cell cycle, and increasing DNA damage in MM cells. These findings pave the way for improved relapse prediction and innovative treatments for MM.

 

 

"The prognostic value of the platelet-to-lymphocyte ratio in multiple myeloma patients treated with a bortezomib-based regimen"

Source

Zhang, Q., Wang, Y., Shi, W. et al. The prognostic value of the platelet-to-lymphocyte ratio in multiple myeloma patients treated with a bortezomib-based regimen. Sci Rep 15, 1819 (2025). https://doi.org/10.1038/s41598-024-84343-x  January 13, 2025. 

Overview

A new study explored the role of the platelet-to-lymphocyte ratio (PLR) as a prognostic marker in multiple myeloma (MM) patients undergoing bortezomib-based chemotherapy.  

Researchers analyzed data from 122 newly diagnosed MM patients, dividing them into low-PLR and high-PLR groups based on initial PLR values. The findings revealed that patients with a low PLR had significantly worse overall survival (OS) and progression-free survival (PFS) compared to those with a high PLR. This pattern held true even in higher-risk MM patients, where a low PLR was linked to poor outcomes.  

Using advanced statistical models, the study also confirmed a nonlinear relationship between PLR and OS, highlighting the potential of PLR as a reliable and independent prognostic tool. These results suggest that monitoring PLR could help guide treatment decisions and provide insight into patient survival in MM.

 

 

"Targeting deubiquitinase USP7-mediated stabilization of XPO1 contributes to the anti-myeloma effects of selinexor"

Source

Wang, J., Chen, M., Jiang, J. et al. Targeting deubiquitinase USP7-mediated stabilization of XPO1 contributes to the anti-myeloma effects of selinexor. J Transl Med 23, 62 (2025). https://doi.org/10.1186/s12967-025-06068-3  January 13, 2025. 

Overview

A new study explored the role of the platelet-to-lymphocyte ratio (PLR) as a prognostic marker in multiple myeloma (MM) patients undergoing bortezomib-based chemotherapy.  

Researchers analyzed data from 122 newly diagnosed MM patients, dividing them into low-PLR and high-PLR groups based on initial PLR values. The findings revealed that patients with a low PLR had significantly worse overall survival (OS) and progression-free survival (PFS) compared to those with a high PLR. This pattern held true even in higher-risk MM patients, where a low PLR was linked to poor outcomes.  

Using advanced statistical models, the study also confirmed a nonlinear relationship between PLR and OS, highlighting the potential of PLR as a reliable and independent prognostic tool. These results suggest that monitoring PLR could help guide treatment decisions and provide insight into patient survival in MM.

 

 

"MicroRNA Profiling of Bone Marrow Plasma Extracellular Vesicles in Multiple Myeloma, Extramedullary Disease, and Plasma Cell Leukemia"

Source

Gregorova, J., Vlachova, M., Vychytilova-Faltejskova, P., Dostalova, A., Ruzickova, T., Vecera, M., Radova, L., Pospichalova, V., Sladecek, S., Hyzdalova, M., Kotaskova, J., Jarosova, M., Masek, J., Benesova, K., Jarkovsky, J., Rihova, L., Bezdekova, R., Almasi, M., Boichuk, I., Stork, M., Pour, L. and Sevcikova, S. (2025), MicroRNA Profiling of Bone Marrow Plasma Extracellular Vesicles in Multiple Myeloma, Extramedullary Disease, and Plasma Cell Leukemia. Hematological Oncology, 43: e70036. https://doi.org/10.1002/hon.70036  January 13, 2025. 

Overview

Multiple myeloma (MM) involves the abnormal production of monoclonal immunoglobulins. While treatments have improved, some patients progress to more aggressive forms, such as extramedullary disease or plasma cell leukemia. Though the exact causes of this progression are unclear, recent studies suggest that small extracellular vesicles containing microRNAs play a role.  

In this study, researchers analyzed bone marrow plasma samples from patients with multiple myeloma, extramedullary disease, and plasma cell leukemia to identify microRNAs involved in disease progression. Using small RNA sequencing, they found 42 microRNAs that were significantly altered across these patient groups. Further validation using RT-qPCR confirmed higher levels of miR-140-3p, miR-584-5p, miR-191-5p, and miR-143-3p in multiple myeloma patients compared to those with other forms of the disease.  

The study also revealed significant links between microRNA levels and clinical characteristics, suggesting that the dysregulation of these molecules could contribute to the progression of multiple myeloma.

 

 

"Ligand-based cheminformatics and free energy-inspired molecular simulations for prioritizing and optimizing G-protein coupled receptor kinase-6 (GRK6) inhibitors in multiple myeloma treatment"

Source

Arnab Bhattacharjee, Supratik Kar, Probir Kumar Ojha, Ligand-based cheminformatics and free energy-inspired molecular simulations for prioritizing and optimizing G-protein coupled receptor kinase-6 (GRK6) inhibitors in multiple myeloma treatment, Computational Biology and Chemistry, 2025, 108347, ISSN 1476-9271, https://doi.org/10.1016/j.compbiolchem.2025.108347. January 13, 2025.  

Overview

Recent studies have highlighted the importance of GRK6 in maintaining multiple myeloma (MM) cell survival, making it a target for new therapies. However, no previous studies have explored inhibitors specifically for GRK6.

In this study, researchers used advanced computational methods to identify potential GRK6 inhibitors. They began by analyzing the structure of GRK6 and how certain chemical features could enhance inhibition. For example, hydrogen bonding and polar interactions improved GRK6 inhibitory activity, while certain electron-accessible groups could lead to off-target effects. They then screened 12,557 compounds from DrugBank, using these findings to identify 7 promising drug leads.

After further testing, they generated 350 potential analogs and analyzed the top 4 using various molecular techniques. One particular compound, DB07168-A13, showed strong potential with promising binding energy and docking scores. The researchers believe this compound should be tested further to see if it could lead to new treatments for multiple myeloma.

 

 

"Delayed neutrophil recovery following BCMA CAR-T therapy in Duffy-null myeloma does not impact severe infections or survival"

Source

Zachary M. Avigan, Saoirse Bodnar, Darren Pan, Jerrel Catlett, Joshua Richter, Larysa J. Sanchez, Cesar Rodriguez, Adriana C. Rossi, Shambavi Richard, Sundar Jagannath, Hearn Jay Cho, Samir Parekh, Santiago Thibaud; Delayed neutrophil recovery following BCMA CAR-T therapy in Duffy-null myeloma does not impact severe infections or survival. Blood Adv 2025; 9 (1): 202–206. doi: https://doi.org/10.1182/bloodadvances.2024014255  January 14, 2025. 

Overview

Chimeric Antigen Receptor T-cell (CAR-T) therapy targeting BCMA has shown promise in treating multiple myeloma (MM), but some patients experience delayed recovery of neutrophil counts, which can lead to infections and disease progression. Previous studies have identified several risk factors for delayed neutrophil recovery, including age and inflammation, but little is known about how the Duffy-null genotype, common in people of African descent, might affect recovery.  

This study aimed to examine the role of the Duffy-null genotype in neutrophil recovery after BCMA-directed CAR-T therapy in MM patients. The researchers found that while both Duffy-null and non-null patients had similar baseline characteristics, Duffy-null patients had significantly slower neutrophil recovery, taking an average of 68 days compared to 40 days in non-null patients. However, Duffy-null patients did not experience worse outcomes in terms of progression-free survival or overall survival, and their risk for severe infections was similar to non-null patients when excluding mild viral infections.  

The study suggests that while Duffy-null patients may experience delayed neutrophil recovery, it does not seem to affect their long-term treatment outcomes. This highlights the need for tailored post-treatment care for Duffy-null individuals and calls for further research to establish guidelines for monitoring and supporting these patients during CAR-T therapy.

 

 

"Spot Urine Protein/Creatinine Ratio as an Alternative to 24-Hour Urine Collection for Measuring Proteinuria in Patients With Multiple Myeloma: A Prospective Study, Clinical Lymphoma Myeloma and Leukemia"

Source

Saad Jamshed, Mohammad Ammad-Ud-Din, Kimberly Celotto, Irfan Ul Haq Minhas, Jonathan Bress, Jens Hillengass, Spot Urine Protein/Creatinine Ratio as an Alternative to 24-Hour Urine Collection for Measuring Proteinuria in Patients With Multiple Myeloma: A Prospective Study, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.01.003. January 13, 2025. 

Overview

In diagnosing and monitoring multiple myeloma (MM) and other plasma cell disorders, 24-hour urine protein tests are commonly used to check for kidney problems, like nephrotic syndrome. However, this test is time-consuming and inconvenient, leading many medical centers to explore quicker options. One potential alternative is the spot urine protein-to-creatinine ratio (SUPC), but research on how well SUPC matches the 24-hour test has been limited.  

A new study involving 40 MM patients found that SUPC and 24-hour urine protein measurements are closely correlated, suggesting that SUPC could be a reliable and easier alternative for monitoring kidney health in these patients. The next step will be to confirm these findings with larger groups of patients, including those with early-stage plasma cell disorders and other related conditions like light chain amyloidosis.

 

 

"Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma"

Source

Grace M. Ferri, Cenk Yildirim, Nhan V. Do, Mary Brophy, Joseph S. Park, Nikhil C. Munshi, Nathanael R. Fillmore, Camille V. Edwards; Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma. Blood Adv 2025; 9 (1): 78–88. doi: https://doi.org/10.1182/bloodadvances.2024014125  January 14, 2025.  

Overview

The bone marrow environment plays a crucial role in the growth and survival of multiple myeloma (MM) cells, helping to promote cancer cell growth while suppressing the immune system’s ability to fight the disease. While factors like clinical and genetic markers are used to assess risk in MM, the immune status is becoming increasingly recognized as a key factor in disease progression, especially with the rise of immune-based therapies.  

A recent study looked at the absolute lymphocyte count (ALC) in the blood of 11,427 MM patients to evaluate its role as a marker of immune health at the time of diagnosis and during treatment. The study found that more than half of the patients had low lymphocyte counts (lymphopenia) at diagnosis. Those with severely low or low ALC had significantly shorter overall survival compared to those with normal ALC levels. Additionally, lymphopenia that persisted or developed during treatment was linked to poorer survival outcomes.  

These results suggest that ALC could be used as an important biomarker for risk assessment and help guide treatment decisions for MM patients.

 

 

"Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis"

Source

Amneet Bajwa, Qiuhong Zhao, Marcus Geer, Chenyu Lin, James Westholder, Joseph Maakaron, Monalisa Ghosh, David Frame, Ahmed Galal, Justin Tossey, Nausheen Ahmed, Evandro Bezerra, Nathan Denlinger, Marcos de Lima, Narendranath Epperla, Paolo Caimi, Timothy Voorhees; Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis. Blood Adv 2025; 9 (1): 170–175. doi: https://doi.org/10.1182/bloodadvances.2024013688  January 14, 2025. 

Overview

Chimeric antigen receptor T-cell (CAR-T) therapies are effective in treating certain blood cancers, but they can cause serious side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). These conditions can be hard to treat, especially when they don’t respond to standard treatments. Siltuximab, a monoclonal antibody that targets a protein called interleukin-6, has been suggested as a possible treatment for both CRS and ICANS.  

A study looking at 54 patients from six academic centers found that siltuximab helped reduce the severity of CRS in 75% of patients and improved ICANS symptoms in 60% of patients. This is the largest group of patients treated with siltuximab for these conditions after CAR-T therapy. The results suggest that siltuximab is effective in managing CRS and ICANS, even in patients who had already received other treatments. These findings support further research into siltuximab for CRS and ICANS treatment.

 

 

"Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial"

Source

Marc-Andrea Baertsch, Jana Schlenzka, Thomas Hielscher, Marc S. Raab, Sandra Sauer, Maximilian Merz, Elias K Mai, Carsten Müller-Tidow, Steffen Luntz, Anna Jauch, Peter Brossart, Martin Goerner, Stefan Klein, Bertram Glass, Peter Reimer, Ullrich Graeven, Roland Fenk, Mathias Haenel, Ivana von Metzler, Hans-Walter Lindemann, Christof Scheid, Igor-Wolfgang W. Blau, Hans J Salwender, Richard Noppeney, Britta Besemer, Katja C. Weisel, Hartmut Goldschmidt; Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial. Blood 2025; blood.2024027342. doi: https://doi.org/10.1182/blood.2024027342  January 14, 2025. 

Overview

The GMMG ReLApsE trial tested whether adding salvage high-dose chemotherapy (sHDCT) and autologous stem cell transplant (ASCT) could help patients with relapsed or refractory multiple myeloma (RRMM) after initial stem cell transplants. In this study, 277 patients were randomly assigned to two groups: one received lenalidomide/dexamethasone (LEN/DEX) and the other received the salvage stem cell transplant along with LEN/DEX maintenance after the transplant. The trial found no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, suggesting that the additional transplant treatment did not offer any clear benefit after frontline stem cell transplant. This means that salvage stem cell transplant is not recommended for patients with RRMM who have already undergone a prior stem cell transplant.

 

 

"Pomalidomide improved immune profiles in myeloma"

Source

Seah H., Bade V., Potluri L., Talluri S., Prabhala R. Pomalidomide improved immune profiles in myeloma. Oncoscience. 2025; 12:1-2. https://doi.org/10.18632/oncoscience.612  January 14, 2025.  

Overview

In patients with relapsed or refractory multiple myeloma (RRMM), the immune system often becomes weakened, making treatment harder. This study investigated the immune system changes in RRMM patients treated with pomalidomide (POM), a drug that helps boost immune function, combined with Velcade and dexamethasone (PVd), compared to treatment with Velcade and dexamethasone alone (Vd). 

Researchers found that POM improved certain immune cells, helping counteract the immune suppression seen in patients treated with Vd. Specifically, POM restored immune cells that were less active in Vd-treated patients, and this immune boost was linked to longer progression-free survival (PFS), meaning patients lived longer without their disease worsening. These findings show that POM helps stimulate the immune system, which may explain its effectiveness in treating RRMM, especially after patients have already been treated with other immunomodulatory drugs like lenalidomide.

 

 

"MRD-negative duration following latest line of therapy predicts long-term PFS in real-world patients with multiple myeloma"

Source

Lucia Y. Chen, Santiago Thibaud, Saoirse Bodnar, Ajai Chari, Joshua Richter, Hearn Jay Cho, Larysa J. Sanchez, Cesar Rodriguez, Adriana C. Rossi, Shambavi Richard, Samir Parekh, Sundar Jagannath; MRD-negative duration following latest line of therapy predicts long-term PFS in real-world patients with multiple myeloma. Blood Adv 2025; 9 (1): 176–179. doi: https://doi.org/10.1182/bloodadvances.2024014097  January 14, 2025.  

Overview

Minimal residual disease (MRD) negativity is a strong indicator of how well multiple myeloma (MM) patients are responding to treatment, and it helps predict their chances of staying in remission. Recent research from the Icahn School of Medicine at Mount Sinai focused on MM patients who were MRD-negative for at least 5 years after their latest treatment. This study aimed to understand the long-term effects of MRD negativity and how long it might take before patients can safely stop maintenance therapy.

The study followed 120 patients who were in complete remission (CR) and MRD-negative for at least 3 consecutive years. Results showed that those who stayed MRD-negative for 5 years had a very low relapse rate—just 11% at 9 years, with most of these patients off therapy. Additionally, patients who had 4 or 5 years of MRD-negativity experienced even better progression-free survival (PFS). The data suggest that patients who achieve MRD negativity for longer periods may have a much lower risk of relapse, and that stopping therapy might be safe after 3 years of sustained MRD negativity.

The study also highlighted that the duration of MRD negativity is an important factor. While current guidelines define sustained MRD negativity as 2 results at least a year apart, the findings suggest that 3 years of MRD negativity might be needed to predict long-term relapse-free survival.

This research underscores the importance of long-term MRD negativity as a sign of durable remission, and suggests that longer durations of MRD negativity could be crucial in determining when to stop maintenance therapy. However, more studies with larger patient groups and longer follow-up are needed to confirm these findings.

 

 

"Socioeconomic, Race-Ethnicity, Household, and Infrastructure Disparities of Hematologic Cancer Outcomes in the US"

Source

David Jun Fei-Zhang, Erik Wu, Alexander Stanisic, Lifang Hou, Leonidas C Platanias, Stephen M. Ansell, Marquita W Lewis, Sherif M. Badawy, Jonas Paludo; Socioeconomic, Race-Ethnicity, Household, and Infrastructure Disparities of Hematologic Cancer Outcomes in the US. Blood Adv 2025; bloodadvances.2024013956. doi: https://doi.org/10.1182/bloodadvances.2024013956 January 14, 2025.   

Overview

Recent research explored how social factors like socioeconomic status, race, and housing affect the outcomes of patients with blood cancers (hematologic malignancies). Using the Social Vulnerability Index (SVI), which measures factors like income, education, and housing in different regions, the study looked at the connection between these social factors and survival rates in 796,005 adults diagnosed with hematologic cancers between 1975 and 2017.

The study found that higher levels of social vulnerability were linked to shorter survival times and less frequent follow-up care for patients with many types of blood cancers. For example, patients with acute lymphocytic leukemia (ALL) had a 33.4% shorter surveillance period, and those with Hodgkin’s lymphoma had a 47.2% shorter survival period when facing higher levels of vulnerability. 

The research showed that factors such as socioeconomic status and housing conditions had the biggest negative impact on survival, followed by language barriers and family structure. These findings suggest that addressing specific social vulnerabilities could improve outcomes for patients with hematologic cancers, pointing to areas for further research and policy changes aimed at reducing health disparities.

 

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"Decreased STING predicts adverse efficacy in bortezomib regimens and poor survival in multiple myeloma"

Source

Liu, Y., Zhao, Y., Li, B. et al. Decreased STING predicts adverse efficacy in bortezomib regimens and poor survival in multiple myeloma. Clin Exp Med 25, 37 (2025). https://doi.org/10.1007/s10238-025-01561-x  January 14, 2025.   

Overview

STING (stimulator of interferon genes) plays a key role in the immune system's defense against infections. Because patients with multiple myeloma (MM) are more vulnerable to infections, this study aimed to understand how STING affects MM and its potential as a treatment target.

Researchers measured STING levels in the bone marrow of MM patients using immunohistochemistry, PCR tests, and flow cytometry. They found that STING levels were much lower in MM tissues compared to normal tissues, and its levels did not depend on the disease stage. Importantly, low STING expression was linked to poorer outcomes for patients treated with bortezomib, a common chemotherapy drug used in MM. Patients with low STING expression were less likely to achieve remission, and their overall survival predictions improved when STING was included in a risk model.

Additionally, patients with low STING expression were more likely to suffer from bacterial infections and had longer treatments with antibiotics. Their immune systems were less active, showing lower levels of neutrophils and other immune cells.

This study suggests that STING plays a crucial role in the immune response of MM patients and could be a promising target for future immunotherapies.

 

 

"Pathophysiologie des multiplen Myeloms"

Source

Jung, J., Nickel, K., Högner, M. et al. Pathophysiologie des multiplen Myeloms. (Pathophysiology of multiple myeloma) Onkologie (2025). https://doi.org/10.1007/s00761-024-01664-2  January 14, 2025.   

Overview

Multiple myeloma (MM) often starts as a stage with no symptoms, where plasma cell numbers are low, and a protein appears in the blood, but no organ damage has occurred yet.

While the exact cause of MM is still not fully understood, early changes in the cell cycle, like problems with certain genes in B-cells, play an important role in the development of the disease. Some common genetic changes in MM include abnormalities in chromosomes and gene translocations, which can also appear in individuals with a condition called monoclonal gammopathy of undetermined significance (MGUS).

MM is genetically diverse, with mutations in key signaling pathways like NFKB and MAPK being frequent. Epigenetic changes (alterations in gene expression) and changes in protein regulation also contribute to the disease. The tumor microenvironment—the surrounding cells and tissues—supports MM cell survival and can make treatment less effective.

Understanding the causes of MM can lead to the development of new treatments, especially for high-risk patients.

 

 

"Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach"

Source

Rujirachaivej, P., Siriboonpiputtana, T., Choomee, K. et al. Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach. J Transl Med 23, 54 (2025). https://doi.org/10.1186/s12967-024-05923-z January 13, 2025.    

Overview

While treatments like CAR T-cell therapy targeting BCMA have shown promise in multiple myeloma (MM), challenges such as resistance and the tumor environment remain. Bispecific T-cell engaging (BITE) antibodies also face issues like short half-lives and possible side effects.

To address these challenges, researchers developed a new therapy using engineered T cells that secrete bispecific molecules (αB7-H3-αCD3 ENG-T cells). These cells were tested against MM cells with different levels of B7-H3 expression, a protein found on some MM cells.

The engineered T cells showed strong anti-tumor effects on MM cells expressing B7-H3, especially at higher concentrations of the cells. They were effective at killing B7-H3-positive MM cells like NCI-H929, L-363, and KMS-12-PE, with higher cytotoxicity observed at increased ratios of T cells to target cells. Cells with no B7-H3 expression (SupT-1) were not affected by the T-cell therapy.

These findings suggest that αB7-H3-αCD3 ENG-T cells could become a promising treatment for B7-H3-positive MM, potentially improving current therapies and patient outcomes. Further studies are needed to explore their full potential.

 

 

"Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma"

Source

Johannes M. Waldschmidt, Noori Sotudeh, Sankalp Arora, Tushara Vijaykumar, Praveen Anand, Hannah Stuart, Julia Frede, Timothy B. Campbell, Shari Kaiser, Xirong Zheng, Nikhil C. Munshi, Kenneth C. Anderson, Hermann Einsele, Andrew J. Yee, Birgit Knoechel, Jens G. Lohr, Noopur S. Raje; Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma. Blood Adv 2025; bloodadvances.2024015285. doi: https://doi.org/10.1182/bloodadvances.2024015285  January 15, 2025.    

Overview

In multiple myeloma (MM), one challenge with T-cell therapies like CAR-T is their effectiveness and long-term success. Researchers are exploring how combining nivolumab, a type of drug that blocks PD-1, with other treatments could help patients whose CAR-T therapy stopped working.

The study found that the response to PD-1 inhibition after CAR-T therapy depends on the health or "fitness" of non-CAR T cells in the patient’s body. By analyzing blood samples from patients, they discovered that T-cell fitness could be a key factor in predicting which patients might respond better to the treatment.

This research suggests that nivolumab-based therapy could be a good option for patients who have become resistant to CAR-T therapy. However, more research is needed to understand how to improve and maintain the effectiveness of these treatments.

 

 

"Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study"

Source

Moreau, P., Facon, T., Usmani, S.Z. et al. Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study. Leukemia (2025). https://doi.org/10.1038/s41375-024-02506-1  January 15, 2025. 

Overview

In the MAIA study, patients with newly diagnosed multiple myeloma (NDMM) who were not eligible for a stem cell transplant showed better results when treated with daratumumab, lenalidomide, and dexamethasone (D-Rd) compared to lenalidomide and dexamethasone alone (Rd). This post hoc analysis, with a follow-up of over five years, focused on specific groups of patients. 

The results showed that D-Rd significantly improved progression-free survival (PFS) in most patient groups, including those aged 75 and older, frail patients, and those with high-risk genetic features. Additionally, patients treated with D-Rd had better overall response rates (ORR) and higher rates of measurable residual disease (MRD)-negativity, which means fewer cancer cells remained detectable. In patients aged 75 or older, the side effects were similar between D-Rd and Rd, but fewer patients stopped treatment due to side effects with D-Rd.

These findings support the use of D-Rd as a standard treatment for transplant-ineligible patients with NDMM, particularly for those with higher-risk features.

 

 

"Exosomal tRF-1003 induces angiogenesis via regulating the HIF1α/VEGF signaling in multiple myeloma"

Source

Yunfeng Fu, Jianyao Sang, Fangrong Zhang, Siyi Jiang, Fangfang Li, Ting Liang, Cong Xu, Exosomal tRF-1003 induces angiogenesis via regulating the HIF1α/VEGF signaling in multiple myeloma, International Immunopharmacology, Volume 146, 2025, 113862,ISSN 1567-5769, https://doi.org/10.1016/j.intimp.2024.113862. January 27, 2025. 

Overview

This study investigates the role of exosomal tRF-1003 in the progression of multiple myeloma (MM), focusing on its impact on angiogenesis, which is the formation of new blood vessels. Angiogenesis is critical for tumor growth and spread, and it is driven by various non-coding RNAs, including tRFs like tRF-1003. The research found that tRF-1003 levels were elevated in the serum exosomes of patients with relapsed and refractory multiple myeloma (R/RMM), indicating that it plays a key role in disease progression.

The study demonstrated that exosomal tRF-1003 can be absorbed by endothelial cells, which line blood vessels, and promote angiogenesis both in laboratory tests and animal models. tRF-1003 enhances blood vessel formation by activating the HIF-1α/VEGF signaling pathway, a known driver of angiogenesis, through the downregulation of MAPK1 expression. Interestingly, overexpressing MAPK1 in endothelial cells partially reversed the angiogenic effects of tRF-1003, confirming the important role of MAPK1 in this process. These findings suggest that exosomal tRF-1003 is a significant contributor to angiogenesis in MM, providing new insights into the molecular mechanisms behind the disease. Targeting tRF-1003 could offer a potential therapeutic approach for managing multiple myeloma.

 

 

"Level of Clonal Plasma Cells in Hematopoietic Cell Autografts Reflects the Pre-Transplant Bone Marrow Minimal Residual Disease in Multiple Myeloma Patients"

Source

Venglar, O., Radova, E., Zihala, D., Tvrda, I., Kubala, V., Kutejova, K., Muronova, L., Kapustova, V., Broskevicova, L., Vrana, J., Popkova, T., Mihalyova, J., Plonkova, H., Sevcikova, T., Kascak, M., Navratil, M., Koristek, Z., Hajek, R. and Jelinek, T. (2025), Level of Clonal Plasma Cells in Hematopoietic Cell Autografts Reflects the Pre-Transplant Bone Marrow Minimal Residual Disease in Multiple Myeloma Patients. Am J Hematol. https://doi.org/10.1002/ajh.27590  January 15, 2025. 

Overview

In this study, researchers examined the role of graft minimal residual disease (gMRD) in predicting outcomes for patients with multiple myeloma (MM) who are undergoing autologous stem cell transplantation (ASCT). The goal was to explore whether gMRD, which measures the presence of cancer cells in stem cell grafts, could serve as a reliable alternative to more invasive bone marrow tests (BM MRD) before the transplant. The study involved 99 transplant-eligible MM patients and found that gMRD positivity was strongly linked to worse progression-free survival (PFS) and overall survival (OS). Patients with gMRD+ were more likely to have higher levels of MRD in their bone marrow both before and after the transplant.

The study also revealed that gMRD could predict pre-ASCT bone marrow MRD status, offering a less invasive method for assessing disease levels. Researchers found that all gMRD+ patients had detectable MRD in their bone marrow before the transplant, and gMRD levels were consistently higher than those in the grafts. These results suggest that gMRD assessment could potentially replace bone marrow aspiration in many patients, reducing procedural burden. The findings also support using gMRD as a tool to better understand disease progression and tailor treatments for patients with multiple myeloma.

 

 

"Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies"

Source

Zhang, Chenyun, Liu, Haizhou, Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies, Journal of Immunology Research, 2025, 5845167, 11 pages, 2025. https://doi.org/10.1155/jimr/5845167  January 15, 2025. 

Overview

In recent years, CAR-T therapy has become a major breakthrough in cancer treatment, especially for blood cancers. One exciting development is dual-target CAR-T therapy, which is designed to recognize two different antigens on tumor cells. This approach offers several benefits over single-target CAR-T therapies, such as better anti-cancer effects, preventing tumors from escaping treatment, reducing harmful side effects, and leading to longer-lasting responses. Dual-target CAR-T has shown promise in both lab and clinical studies across various types of cancers. This review looks at these studies, focusing on the combination of targets used, the effectiveness and safety in preclinical and clinical trials, as well as the challenges and future potential of this innovative treatment strategy.

 

 

"Aurore Perrot; Daratumumab for maintenance in myeloma"

Source

Cyrille Touzeau, Aurore Perrot; Daratumumab for maintenance in myeloma. Blood 2025; 145 (3): 251–252. doi: https://doi.org/10.1182/blood.2024026888  January 16, 2025. 

Overview

The AURIGA study compared two treatments for patients with newly diagnosed multiple myeloma (NDMM) after a stem cell transplant. The study looked at adding daratumumab (a drug that targets CD38) to lenalidomide (DR) versus using lenalidomide alone (R) as maintenance therapy. It showed that adding daratumumab significantly increased the rate of minimal residual disease (MRD) negativity, meaning the patients had less cancer left after treatment. The DR group also showed better progression-free survival, meaning they had less disease progression or death over time. The DR regimen was well tolerated without new safety concerns.

However, the study has some limitations. It focused on patients with detectable MRD before maintenance, and it didn't answer whether adding daratumumab benefits patients who were already in remission before starting maintenance. More research is needed to confirm whether the addition of daratumumab is useful in other groups of patients, especially those who received other treatments before maintenance. Despite these unanswered questions, the study results suggest that combining daratumumab with lenalidomide during maintenance could help improve outcomes for certain multiple myeloma patients.

 

 

"Is it time to screen for multiple myeloma?"

Source

Irene M. Ghobrial, Floris Chabrun; Is it time to screen for multiple myeloma?. Blood 2025; 145 (3): 253–255. doi: https://doi.org/10.1182/blood.2024027065  January 16, 2025. 

Overview

In this study, Visram and colleagues explore whether monoclonal gammopathy (MGUS) detected through screening is the same as MGUS found incidentally during testing for other conditions. The study found that the risk of progression to multiple myeloma (MM) is similar for both screened and incidentally detected MGUS. Factors that affect progression, like the size of the M spike and the ratio of free light chains, were consistent regardless of how MGUS was detected.

MGUS and smoldering myeloma (SMM) are early stages of MM, and screening for these conditions could help identify individuals at higher risk, enabling early intervention and better outcomes. However, MGUS is often discovered when testing for other health problems, and it doesn’t always lead to MM. The study shows that progression risks in screened patients are similar to those found incidentally, but further research in more diverse populations is needed.

While there is no current treatment to prevent MGUS from progressing to MM, research is underway to explore early treatments for SMM. Screening could help identify those who would benefit most from these treatments. However, there are concerns about the cost of screening and whether it could cause unnecessary anxiety for patients without treatment options. Ongoing studies like iStopMM and PROMISE will help answer whether early screening and treatment can improve survival. 

In the future, if treatments for asymptomatic MM are proven effective, routine screening could become more widely accepted, leading to earlier diagnosis and better outcomes for patients, especially in high-risk groups like African Americans.

 

 

"Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study"

Source

Ashraf Badros, Laahn Foster, Larry D. Anderson, Chakra P. Chaulagain, Erin Pettijohn, Andrew J. Cowan, Caitlin Costello, Sarah Larson, Douglas W. Sborov, Kenneth H. Shain, Rebecca Silbermann, Nina Shah, Alfred Chung, Maria Krevvata, Huiling Pei, Sharmila Patel, Vipin Khare, Annelore Cortoos, Robin Carson, Thomas S. Lin, Peter Voorhees; Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study. Blood 2025; 145 (3): 300–310. doi: https://doi.org/10.1182/blood.2024025746  January 16, 2025. 

Overview

The AURIGA study compared two treatment options for patients with newly diagnosed multiple myeloma (NDMM) after a stem cell transplant. It looked at the combination of daratumumab and lenalidomide (D-R) versus lenalidomide alone (R) as maintenance therapy. The study found that patients who received D-R had significantly better results in terms of minimal residual disease (MRD) negativity and progression-free survival (PFS) compared to those who received R alone.

After 12 months, 50.5% of patients on D-R achieved MRD negativity at a level of 10–5, compared to only 18.8% for those on R. When looking at a more sensitive level of MRD negativity (10–6), 23.2% of patients on D-R achieved this, compared to just 5.0% on R. The study also showed that D-R therapy led to a higher rate of complete response and better overall progression-free survival.

While there were slightly higher rates of certain side effects, like low blood cell counts and infections, D-R was well-tolerated without any new safety concerns. In conclusion, D-R maintenance therapy provided better outcomes in terms of MRD negativity and PFS after transplant compared to R alone.

 

 

"Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection"

Source

Alissa Visram, Dirk Larson, Aaron Norman, Angela Dispenzieri, David Murray, Robert Kyle, S. Vincent Rajkumar, Susan Slager, Shaji Kumar, Celine Vachon; Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection. Blood 2025; 145 (3): 325–333. doi: https://doi.org/10.1182/blood.2024025415  January 16, 2025. 

Overview

Monoclonal gammopathy of undetermined significance (MGUS) is a condition that doesn't cause symptoms but can sometimes develop into more serious health problems. It is often found by chance during routine tests, as there is no standard screening for it. In this study, researchers compared the progression risk of MGUS between patients who were screened for it and those who had it diagnosed during regular medical visits.

The study included 379 people diagnosed with MGUS through screening and 1,384 who were diagnosed during routine clinical care. After following the patients for many years, the study found that the risk of MGUS turning into a more serious condition was similar for both groups. The progression rate was about the same whether MGUS was detected through screening or during a clinic visit.

The method of detecting MGUS did not change the relationship between known risk factors and disease progression. Overall, the findings suggest that the way MGUS is detected—whether by screening or during regular checkups—does not affect how likely it is to progress to a more serious disease. More research is needed to see if different follow-up approaches for patients diagnosed through screening might improve outcomes.

 

 

"Clarithromycin, Ixazomib, Pomalidomide, Dexamethasone for Relapsed/Refractory Myeloma: Survival and Correlative Analysis"

Source

Aaron S Rosenberg, Emanual Maverakis, Caitlin Costello, Elizabeth A. Brem, Matthew Joseph Wieduwilt, Guillaume Luxardi, Paul Kaesberg, Keon Abedi, Samantha Herbert, Joseph Tuscano, Clarithromycin, Ixazomib, Pomalidomide, Dexamethasone for Relapsed/Refractory Myeloma: Survival and Correlative Analysis, Blood Neoplasia, 2025, 100067, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100067. January 16, 2025. 

Overview

A Phase I/II study investigated the combination of clarithromycin, ixazomib, pomalidomide, and dexamethasone (ClIPd) in patients with relapsed or refractory multiple myeloma (RRMM). The main goal was to assess the treatment's safety, tolerability, and effectiveness. The results showed that 75% of patients responded to the treatment, with 56% achieving a very good partial response (≥VGPR) and 14% reaching complete or stringent complete response. Additionally, the disease control rate was 100%, indicating that all patients had some level of disease stability.

The treatment also demonstrated prolonged disease control, with a median progression-free survival (PFS) of 22.2 months. Importantly, high-risk genetic features, such as del(17p) or +1q, did not significantly affect PFS. ClIPd was well-tolerated with manageable side effects, offering a convenient oral treatment option for patients. Overall, the study suggests that ClIPd may provide long-lasting disease control with a favorable safety profile for patients with RRMM. 

Clinical Trial: NCT02542657

 

 

"Respiratory syncytial virus and other vaccine-preventable infections in multiple myeloma. A population-based study on 8,672 myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry"

Source

Einarsdottir S, Sverrisdottir I, Villegas-Scivetti M, Day C, Turesson I, Juliusson G, Hansson M, Larfors G, Blimark CH. Respiratory syncytial virus and other vaccine-preventable infections in multiple myeloma. A population-based study on 8,672 myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry. Haematologica 2025;110(1):179-182; https://doi.org/10.3324/haematol.2024.285161.  January 2025. 

Overview

Infections are a significant issue for patients with multiple myeloma (MM), due to both the disease and its treatments. This study aimed to understand the risk of vaccine-preventable infections in MM patients compared to healthy individuals. Using real-world data from Sweden, the study included over 8,600 MM patients and compared them to more than 34,500 healthy controls. The results showed that MM patients had a much higher risk of vaccine-preventable infections, especially respiratory syncytial virus (RSV) and pneumococcal infections, which were 16 and 17 times more common, respectively, than in the general population. The risk of infections remained high, especially in the first year after diagnosis and continued to increase over time for certain infections, such as herpes zoster and influenza.

Vaccination is crucial for MM patients to help reduce the severity of these infections. The study highlighted that while vaccinations are underused in MM patients, especially in those receiving modern treatments like immunomodulatory drugs, vaccines such as the pneumococcal, influenza, and RSV vaccines have been shown to reduce disease severity and hospitalization. The study suggests that vaccinations should be more strongly encouraged for MM patients, including those undergoing treatments like CAR T cells or bispecific antibodies, though more data is needed on vaccine responses in these groups. Despite some limitations, such as the lack of vaccination data and potential underreporting of infections, the study emphasizes the need for MM patients to receive vaccines to help prevent severe infections and improve overall health outcomes.

 

 

"Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study"

Source

Merz, M., Albici, A.-M., von Tresckow, B., Rathje, K., Fenk, R., Holderried, T., Müller, F., Tovar, N., Oliver-Cáldes, A., Vucinic, V., Kharboutli, S., Bärmann, B.-N., Ayuk, F., Platzbecker, U., Stölzel, F., Schub, N., Schmitz, F., Fandrei, D., Born, P., Khandanpour, C., Hanoun, C., Hörster, K., Teichert, M., Jeker, B., Hoffmann, M., Kröger, N., de Larrea, C.F., Pabst, T. and Gagelmann, N. (2025), Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study. HemaSphere, 9: e70070. https://doi.org/10.1002/hem3.70070  January 16, 2025 

Overview

This study compared two CAR T-cell therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), for treating relapsed or refractory multiple myeloma (RRMM). Researchers found that cilta-cel had significantly better outcomes than ide-cel. Cilta-cel showed a higher overall response rate (93% vs. 79%) and a higher complete response rate (48% vs. 26%) at 30 days. Additionally, cilta-cel had better progression-free survival (82% vs. 47%) at 10 months, although the overall survival rates were similar (90% for cilta-cel vs. 77% for ide-cel).

Both treatments had similar rates of cytokine release syndrome (CRS) and neurotoxicity (ICANS), but cilta-cel's CRS occurred later and was less severe. The median time between cell collection and infusion was shorter for ide-cel (47 days vs. 68 days). Despite cilta-cel’s superior efficacy, both therapies had manageable safety profiles, with similar rates of severe CRS and ICANS. This real-world evidence suggests that cilta-cel offers better outcomes and has distinct cellular behavior compared to ide-cel in patients with triple-class exposed RRMM.

 

 

"Predictive Role of Soluble B-Cell Maturation Antigen in Short-Term Monitoring of Differently Treated Multiple Myeloma Patients: A Prospective Study"

Source

Caponi, L., Del Giudice, M.L., Botti, A., Ursino, S., Gennari, A., Paolicchi, A., Galimberti, S. and Buda, G. (2025), Predictive Role of Soluble B-Cell Maturation Antigen in Short-Term Monitoring of Differently Treated Multiple Myeloma Patients: A Prospective Study. J Clin Lab Anal e25151. https://doi.org/10.1002/jcla.25151  January 16, 2025.  

Overview

This study explored the use of soluble B-Cell Maturation Antigen (sBCMA) as a biomarker to monitor multiple myeloma, a disease that is difficult to manage due to its relapsing nature. Traditional methods for monitoring myeloma often involve costly or invasive tests, but sBCMA can be detected in blood with a simple, affordable test. The study followed 57 myeloma patients over 6 months and found that sBCMA levels were measurable in all patients, including those with non-secretory disease or on BCMA-targeted therapies. The changes in sBCMA levels over time were linked to the patients' response to treatment. These findings suggest that sBCMA could be a valuable, non-invasive tool for assessing treatment effectiveness and guiding personalized treatment plans for myeloma patients.

 

 

"A systematic epidemiological trends analysis study in global burden of multiple myeloma and 29 years forecast"

Source

Hou, Q., Li, X., Ma, H. et al. A systematic epidemiological trends analysis study in global burden of multiple myeloma and 29 years forecast. Sci Rep 15, 2204 (2025). https://doi.org/10.1038/s41598-024-83630-x  January 16, 2025. 

Overview

New data from the Global Burden of Diseases Study 2021 sheds light on the global impact of multiple myeloma (MM). In 2021, there were around 148,755 new cases of multiple myeloma worldwide, with 116,360 deaths linked to the disease. Over the past three decades, the number of cases, deaths, and years of life lost due to the disease has steadily increased, particularly in high-income countries, though its presence is rising in low-income countries as well. Projections for 2022 to 2050 suggest that the number of cases, deaths, and related health burdens will continue to grow globally. This highlights the ongoing challenge posed by multiple myeloma and the need for continued focus on its prevention and treatment.

 

 

"Evaluation of plasma cell sorting methods in multiple myeloma patients: flow cytometry versus magnetic beads"

Source

Choi, Y.J., Choi, J., Kang, Y. et al. Evaluation of plasma cell sorting methods in multiple myeloma patients: flow cytometry versus magnetic beads. Cancer Cell Int 25, 16 (2025). https://doi.org/10.1186/s12935-025-03647-8  January 17, 2025

Overview

This study compares two techniques for sorting plasma cells from bone marrow samples: fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS). FACS is the current gold standard but requires expensive equipment and long processing times. MACS, on the other hand, is quicker and doesn't need specialized equipment. The study found that MACS sorted bone marrow samples with a higher percentage of plasma cells compared to FACS. Both methods showed similar results in genetic tests, but MACS detected more genetic abnormalities in some cases. The findings suggest that MACS could be a practical and effective alternative to FACS for sorting plasma cells in clinical settings.

 

 

"Are They Ready Yet?”: release criteria for autologous CAR T cells"

Source

Jallouk, A.P., Oluwole, O. & Dholaria, B. “Are They Ready Yet?”: release criteria for autologous CAR T cells. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-024-02482-1  January 17, 2025. 

Overview

This article discusses recommendations from the UNITC consortium about how to handle the release of fresh, locally made autologous CAR T-cell products. These cells are used to treat certain cancers like multiple myeloma, but the process of preparing and releasing them can take weeks. The goal of these recommendations is to streamline the release process while ensuring the quality and safety of the CAR T cells. 

One key recommendation is to allow interim test results—such as sterility and endotoxin detection—to be used for initial certification and clinical use, even before the final test results are available. This could help speed up the process and allow patients to receive treatments more quickly. -The article also highlights the challenges of using fresh CAR-T products, especially since the time in culture can affect their effectiveness. 

New technologies and methods are being developed to speed up CAR Tcell manufacturing, including faster ways to grow the cells. However, the current release testing process still takes time and can slow down treatment. The article suggests improving release testing procedures to keep up with faster manufacturing methods, so patients can get their treatments as soon as possible while maintaining high safety standards.

 

 

"Enhancing staging in multiple myeloma using an m6A regulatory gene-pairing model"

Source

Deng, Y., Zhu, H. & Peng, H. Enhancing staging in multiple myeloma using an m6A regulatory gene-pairing model. Clin Exp Med 25, 40 (2025). https://doi.org/10.1007/s10238-024-01526-6  January 17, 2025. 

Overview

This study developed a new way to predict the prognosis of multiple myeloma (MM) by using a model based on specific genes that regulate a process called m6A. The model successfully divided MM patients into high-risk and low-risk groups, based on their gene patterns. It showed strong performance in predicting how patients would respond to combination therapies, especially for those who relapsed after using bortezomib-based treatments.

The model also helped differentiate between smoldering MM, active MM, and plasma cell leukemia. Through a detailed single-cell analysis, the study found that patients with higher risk scores were more likely to relapse. By combining MM cell lines and patient samples, the researchers identified potential drugs and targets (ADAT2 and NUP153) that might be effective for high-risk MM patients. Integrating this new risk model with the current staging system improved the accuracy of patient predictions, which could help doctors tailor treatments more precisely.

 

 

"Use of disease-modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis"

Source

Tokareva, K., Peterson, A.C., Baraff, A. et al. Use of disease-modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis. BMC Rheumatol 9, 7 (2025). https://doi.org/10.1186/s41927-025-00457-3  January 17, 2025.  

Overview

This study explored whether using biologic (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) affects the risk of developing multiple myeloma (MM). The study used data from the Veterans Health Administration and included veterans diagnosed with RA between 2002 and 2018. The researchers compared veterans who took b/tsDMARDs with those who did not.

The results showed that there was no significant difference in the rate of MM between patients who used b/tsDMARDs and those who used conventional synthetic DMARDs. The study found 77 new cases of MM over nearly 200,000 person-years of follow-up. The risk of MM was slightly higher in those using b/tsDMARDs, but the difference was not large enough to be conclusive. The study's limited follow-up time and small number of MM cases made it difficult to draw firm conclusions about the connection between b/tsDMARDs and MM risk.

 

 

"PD-L1 expression in multiple myeloma myeloid derived suppressor cells, Methods in Cell Biology"

Source

Laura G. Rico, Roser Salvia, Jolene A. Bradford, Michael D. Ward, Jordi Petriz, PD-L1 expression in multiple myeloma myeloid derived suppressor cells, Methods in Cell Biology, Academic Press, 2025, ISSN 0091-679X, https://doi.org/10.1016/bs.mcb.2024.11.006. January 17, 2025.   

Overview

This study focuses on the PD-1/PD-L1 pathway, a key target in cancer immunotherapy, and its role in multiple myeloma (MM). PD-L1, a protein linked to immune evasion and drug resistance, is overexpressed in abnormal plasma cells and myeloid-derived suppressor cells (MDSCs) in MM. However, in MDSCs, PD-L1 often has a conformation that standard monoclonal antibodies cannot detect. When stimulated with PMA, PD-L1 undergoes a structural change that makes it recognizable.

Researchers developed a flow cytometry assay to detect these conformational changes in PD-L1 with minimal sample manipulation, preserving its natural structure and function. Using this method, MM patients can be classified based on how their PD-L1 levels change after stimulation compared to unstimulated samples. The study also outlines protocols for tracking PD-L1 expression over time, comparing its presence on the cell surface versus inside the cell, and testing how durvalumab (a PD-L1 inhibitor) interacts with PD-L1. This technique could be applied to study conformational changes in other proteins as well.

 

 

"A Markov model for estimating the cost-effectiveness of immunotherapy for newly diagnosed multiple myeloma patients"

Source

Massimo Bilancia, Antonio Giovanni Solimando, Fabio Manca, Angelo Vacca, Roberto Ria, A Markov model for estimating the cost-effectiveness of immunotherapy for newly diagnosed multiple myeloma patients, Computational Statistics & Data Analysis, 2025, 108130, ISSN 0167-9473, https://doi.org/10.1016/j.csda.2025.108130. January 17, 2025. 

Overview

Multiple myeloma (MM) is a cancer of plasma cells that begins in B lymphocytes and builds up in the bone marrow. It accounts for 1-1.8% of all cancers and 15% of blood-related cancers, with its prevalence rising in industrialized countries. Immunotherapy has expanded treatment options for MM, offering better results and fewer side effects compared to traditional treatments. Daratumumab, a recently approved monoclonal antibody, has shown significant benefits for patients but comes with high treatment costs, raising concerns about its economic impact.

To evaluate the cost-effectiveness of immunotherapy like daratumumab, researchers developed a six-state Markov model. This tool analyzes the financial and clinical value of these treatments in newly diagnosed MM patients and other blood cancer patients. The model aims to help healthcare providers and policymakers make informed decisions about treatment strategies while considering both patient outcomes and economic sustainability.

 

 

"Clinical Validation of Optical Genome Mapping in Multiple Myeloma Without Plasma Cell Enrichment"

Source

Yoon, J., Kwon, J.A. and Yoon, S.-Y. (2025), Clinical Validation of Optical Genome Mapping in Multiple Myeloma Without Plasma Cell Enrichment. Am J Hematol. https://doi.org/10.1002/ajh.27589  January 17, 2025.  

Overview

Detecting genetic changes is crucial for managing multiple myeloma (MM), especially high-risk markers like translocations, for example, t(4;14), t(14;16), and deletions such as 17p-. Traditional testing methods like fluorescence in situ hybridization (FISH) face challenges, including the need for plasma cell enrichment, larger bone marrow samples, and additional processing steps. Optical genome mapping (OGM) is an emerging technology that addresses these limitations, offering genome-wide analysis without the need for plasma cell enrichment.  

In a recent study, OGM demonstrated a 98.2% concordance with FISH in detecting high-risk genetic changes. It successfully identified translocations at variant allele frequencies (VAFs) as low as 10% and copy number variations (CNVs) above 13.8%. The technology performed best in samples with plasma cell percentages of 21% or higher, emphasizing the importance of sample quality. OGM also provides broader insights by detecting genome-wide abnormalities like hyperdiploidy, which FISH might miss.  

OGM offers a cost-effective and efficient alternative to whole-genome sequencing, simplifying sample processing while improving detection of genetic variations. While additional validation studies are needed, OGM shows promise as a complementary or initial screening tool for MM, providing more comprehensive insights to guide treatment decisions.

 

 

"Invasive Fungal Diseases in Patients with Multiple Myeloma: Experience at a Large, Urban Referral Center"

Source

Baneman, E., Weinberg, A., Sullivan, T., Fuller, R., Dunn, D., Taimur, S., Rana, M. and Jacobs, S.E. (2025), Invasive Fungal Diseases in Patients with Multiple Myeloma: Experience at a Large, Urban Referral Center. Transpl Infect Dis e14439. https://doi.org/10.1111/tid.14439  January 18, 2025.   

Overview

Infections are a major concern for patients with multiple myeloma (MM), but the occurrence and risk factors of invasive fungal disease (IFD) in this group are not well understood. A recent study reviewed 2,960 MM patients treated between 2011 and 2019, identifying 32 cases of IFD. Most patients developed IFD approximately 3.6 years after their MM diagnosis and had undergone multiple treatments, including chemotherapy (median of four lines) and autologous stem cell transplants (53%). At the time of IFD, 72% of patients had progressive disease, and many experienced immune system issues like neutropenia (47%), lymphopenia (41%), and hypogammaglobulinemia (56%).  

The study identified Aspergillus as the most common fungal cause, followed by Candida, Cryptococcus, Mucorales, and Histoplasma. Key risk factors for IFD included progressive MM (odds ratio [OR] 1.35) and neutropenia (OR 17.5). Patients with three or more prior chemotherapy regimens showed a trend toward increased risk (OR 5.6).  

While the overall risk of IFD in MM patients remains low, the findings emphasize the need for heightened awareness and monitoring in patients with advanced disease or significant immune suppression. This study offers valuable insights to guide infection prevention strategies in MM care. 

 

 

"Updates on mechanisms of disease progression in precursor myeloma: Monoclonal gammopathy of undermined significance and smoldering myeloma"

Source

Cynthia Saade, Irene Ghobrial, Updates on mechanisms of disease progression in precursor myeloma: Monoclonal gammopathy of undermined significance and smoldering myeloma, La Presse Médicale, 2025, 104268, ISSN 0755-4982, https://doi.org/10.1016/j.lpm.2025.104268. January 18, 2025  

Overview

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are early, premalignant stages of multiple myeloma (MM). Advances in detection methods, like mass spectrometry, have uncovered even smaller abnormalities, such as monoclonal gammopathy of indeterminate potential (MGIP), which may develop before MGUS.  

Risk models, including Mayo Clinic, PETHEMA, 2/20/20, IMWG, and PANGEA, use tumor markers and genetic abnormalities to predict the likelihood of progression. Genomic studies have revealed mutations and changes in the immune microenvironment that contribute to disease evolution. Epigenetics is also emerging as a factor influencing tumor behavior and progression.  

For high-risk SMM, therapies like lenalidomide, daratumumab, and newer immunotherapies show promise in delaying progression to MM. However, their use in asymptomatic patients raises safety concerns. Future research aims to refine risk models, integrate genetic and immune data, and define the best strategies for early treatment. These advancements highlight the importance of early risk assessment and targeted interventions to improve outcomes for patients at risk of developing MM.

 

 

"Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis"

Source

Gao, X., Feng, Q., Zhang, Q. et al. Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis. J Biomed Sci 32, 9 (2025). https://doi.org/10.1186/s12929-024-01101-x  January 20, 2025. 

Overview

Enolase 1 (ENO1), a key enzyme in glycolysis, plays a larger role in multiple myeloma (MM) than previously understood. This study found that ENO1 is highly expressed in MM patients and is linked to worse outcomes. Beyond its metabolic function, ENO1 supports tumor growth by promoting mitophagy (the removal of damaged mitochondria), which helps MM cells evade apoptosis (programmed cell death), especially during treatment with bortezomib, a common MM drug.  

ENO1 stabilizes the YWHAZ protein, preventing its breakdown and enhancing mitophagy. Blocking ENO1 or using drugs targeting HDAC6 (a regulator of YWHAZ) disrupts this process, making MM cells more sensitive to bortezomib. Combining bortezomib with ENO1 inhibitors showed strong anti-cancer effects in lab and animal studies.  

These findings suggest that targeting ENO1 could be a promising strategy to overcome drug resistance and improve treatment outcomes for MM patients.

 

 

"Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects"

Source

Dona, A.A., Tandoh, T., Nigam, L. et al. Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects. J Hematol Oncol 18, 1 (2025). https://doi.org/10.1186/s13045-024-01645-3  January 20, 2025. 

Overview

Reovirus (RV), a virus that naturally targets cancer cells, has shown promise in treating multiple myeloma (MM). While RV was safe in early studies, it didn’t achieve strong disease control on its own. Researchers discovered that combining RV with proteasome inhibitors (PIs), such as carfilzomib, significantly improves its effectiveness.  

Proteasome inhibitors help RV replicate better in monocytes, immune cells that deliver the virus to myeloma cells. This combination also boosts immune responses, activating T-cells and enhancing the immune system’s ability to kill myeloma cells, even in patients whose cancer no longer responds to PIs alone.  

A phase 1b trial tested this approach in 13 heavily pretreated MM patients. About 70% of patients responded, showing viral replication, T-cell activation, and improved immune responses. These findings suggest PIs can enhance oncolytic virus therapies beyond their traditional cancer-killing roles, offering a new way to improve outcomes for patients with MM and other cancers.

 

 

"Targeting Transcription-Replication Conflicts using G-quadruplexes stabilizers in Multiple Myeloma"

Source

Laure DUTRIEUX, Sara OVEJERO, Antoine GUILLEMIN, Leriem ZELLAGUI, Elke De BRUYNE, Catharina MUYLAERT, Lien VAN HEMELRIJCK, Yea-Lih LIN, Elle LOUGHRAN, Armelle CHOQUET, Talha MAGAT, Soumya BOUCHOUIKA, Caroline BRET, Guilhem REQUIRAND, Nicolas ROBERT, Laure VINCENT, Guillaume CARTRON, Charles HERBAUX, Raphaël RODRIGUEZ, Michel COGNE, Eric RIVALS, Jean-Christophe ANDRAU, Alexandre DAVID, Philippe PASERO, Jérôme MOREAUX, Targeting Transcription-Replication Conflicts using G-quadruplexes stabilizers in Multiple Myeloma, Blood Neoplasia, 2025, 100072, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100072.  January 20, 2025. 

Overview

Multiple myeloma (MM) cells experience high levels of replication stress due to their excessive production of immunoglobulins. This stress creates transcription-replication conflicts (TRCs), where DNA replication and transcription processes collide. These TRCs contribute to genomic instability and drug resistance but also present a unique vulnerability in MM cells.  

Researchers identified a gene signature, the "TRC score," that is higher in MM cells compared to normal plasma cells. Patients with high TRC scores tend to have worse outcomes but may benefit from therapies that increase TRCs. One such approach uses a compound called pyridostatin (PDS), which stabilizes specific DNA structures called G-quadruplexes (G4).  

In laboratory studies, PDS caused significant damage to MM cells, leading to cell cycle arrest and cell death, while sparing healthy bone marrow cells. Additionally, combining PDS with standard MM treatments, like melphalan, HDAC inhibitors, or BRD inhibitors, enhanced their effectiveness.  

This research highlights the potential of G4 stabilizers like PDS as a targeted therapy to exploit MM cells' replication stress, offering a new strategy to improve treatment outcomes.

 

 

"Rare cancer survivorship research funding at the National Institutes of Health (NIH)"

Source

Gallicchio, L., Mollica, M., Tesauro, G. et al. Rare cancer survivorship research funding at the National Institutes of Health (NIH), 2017 to 2023. Cancer Causes Control (2025). https://doi.org/10.1007/s10552-025-01959-8  January 21, 2025.  

Overview

This study aimed to evaluate the National Institutes of Health (NIH) cancer survivorship research portfolio, specifically for rare cancers, and identify areas needing more focus.

The study reviewed NIH grants for rare cancer survivorship research from 2017 to 2023. It found 93 grants awarded in total, with about 85% of them focusing on just four cancer types: leukemia, head and neck cancers, ovarian cancer, and brain cancer. Fewer grants were awarded for other rare cancers like multiple myeloma, testicular cancer, and others. Half of the grants were observational studies, and 34% specifically addressed the needs of pediatric cancer survivors.

The study highlights a significant gap in survivorship research for many rare cancer types. This lack of research limits our understanding of the unique challenges survivors face and the development of effective interventions to help them

 

 

"Blood pressure variability as predictor of cancer therapy-related cardiovascular toxicity in patients with Multiple Myeloma"

Source

Fanelli, E., Picca, G., Airale, L. et al. Blood pressure variability as predictor of cancer therapy-related cardiovascular toxicity in patients with Multiple Myeloma. Hypertens Res (2025). https://doi.org/10.1038/s41440-024-02084-w  January 22, 2025. 

Overview

Blood pressure variability (BPV) has been identified as a predictor of cardiovascular events. This study explored how BPV might also predict cardiovascular toxicity related to cancer treatment (CTR-CVT) in patients with multiple myeloma undergoing proteasome inhibitor therapy.

The study involved 124 patients who underwent various tests, including blood pressure monitoring, echocardiography, and pulse wave velocity measurements. It found that patients who developed CTR-CVT had higher BPV at baseline. Notably, higher BPV during the night was linked to an increased risk of CTR-CVT, even after accounting for other factors like age, smoking, and kidney function. Specific BPV thresholds during the night were identified as predictors for CTR-CVT.

The study also identified certain subgroups of patients with the highest BPV who experienced more cardiovascular events. These findings suggest that BPV can help better predict cardiovascular risks in cancer patients, offering a more precise way to identify individuals at higher risk, beyond what traditional methods can detect.

 

 

"Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma"

Source

Yakinthi Chrisochoidou, Andrea Scarpino, Salomon Morales, Shannon Martin, Sarah Anne Bird, Yigen Li, Brian A Walker, John Caldwell, Yann-Vai Le Bihan, Charlotte Pawlyn; Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma. Blood 2025; blood.2024025861. doi: https://doi.org/10.1182/blood.2024025861  January 22, 2025. 

Overview

Resistance to immunomodulatory drugs (IMiDs) is a major challenge in treating multiple myeloma. Some patients develop mutations in a protein called cereblon (CRBN), which affects how IMiDs work. While certain mutations, like stop codons or frameshifts, clearly impact CRBN function, the effect of missense mutations (a change in one amino acid) on CRBN had not been fully studied.

This research focused on understanding the effects of missense mutations on CRBN and whether newer drugs, called cereblon binding agents (CELMoDs), could overcome these mutations. The study found three main patterns of mutation response: some mutations completely blocked CRBN function, others had no effect, and some only affected CRBN’s function with certain drugs. Further tests showed that the more potent CELMoDs could still cause cancer cell death, even when IMiDs were ineffective.

These findings are important for myeloma treatment. They suggest that patients with certain CRBN mutations, even if they are resistant to IMiDs, might still benefit from CELMoD agents. This research helps guide future treatment decisions for patients with CRBN mutations.

 

 

"Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial"

Source

Aurore Perrot, Cyrille Touzeau, Jerome Lambert, Cyrille Hulin, Denis Caillot, Lionel Karlin, Bertrand Arnulf, Philippe Rey, Laurent Garderet, Margaret Macro, Martine Escoffre-Barbe, Julie Gay, Thomas Chalopin, Romain Gounot, Jean Marc Schiano de Colella, Mourad Tiab, Mohamad Mohty, Frédérique Kuhnowski, Jean Fontan, Salomon Manier, Frederique Orsini Piocelle, Laure Vincent, Sophie Rigaudeau, Xavier Leleu, Benjamin Hébraud, Laurent Flet, Jean-Valère Malfuson, Caroline Jacquet, Driss Chaoui, Nathalie Meuleman, Wajed Abarah, Lydia Montes, Riad Benramdane, Cécile Sonntag, Hacene Zerazhi, Alina Danu, Olivier Allangba, Mamoun Dib, Murielle Roussel, Sophie Cereja, Julien Depaus, Nicolas Branche, Hélène Demarquette, Valentine Richez, Cherel Bruiec, Laurent Frenzel, Marie-Christiane MB Vekemans, Noemie Bigot, Hervé Avet-Loiseau, Jill Corre, Philippe Moreau; Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial. Blood 2025; blood.2024026230. doi: https://doi.org/10.1182/blood.2024026230  January 22, 2025.  

Overview

A phase III study (IFM2020-02-MIDAS) assessed the use of a treatment regimen called IsaKRD, which combines isatuximab, carfilzomib, lenalidomide, and dexamethasone, before an autologous stem cell transplant for newly diagnosed multiple myeloma patients. The study focused on whether this treatment strategy, driven by minimal residual disease (MRD), could improve outcomes.

The study involved 791 patients, with a median age of 59, and included various stages of the disease and risk factors. The treatment regimen showed strong results, with 96% of patients completing the induction phase, and 95% of patients achieving a positive overall response. MRD-negativity, which suggests the absence of detectable cancer, was seen in 63% of patients at a high sensitivity level. 

While IsaKRD showed good safety, with only 13% of patients reporting peripheral neuropathy and common side effects including neutropenia (low white blood cells) and infections, the treatment did not lead to any new safety concerns. 

The study demonstrated that IsaKRD provided deep responses and successfully collected stem cells for transplant. However, more follow-up is needed to confirm these findings long-term.

 

 

"T cell redirection as a new standard of care for relapsed multiple myeloma: impact on inpatient capacity, financial burden and infrastructural requirements in German"

Source

Ahmadi, P., Alsdorf, W., Leypoldt, L. et al. T cell redirection as a new standard of care for relapsed multiple myeloma: impact on inpatient capacity, financial burden and infrastructural requirements in Germany. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-024-02505-x  January 22, 2025. 

Overview

New immunotherapy options, like CAR-T cell therapy and bispecific antibodies (bsAbs), are improving outcomes and extending survival for multiple myeloma patients whose disease has become resistant to therapy. However, these treatments often require hospitalization for careful monitoring of potential side effects, such as cytokine release syndrome (CRS) and neurotoxicity.  

CAR-T therapies, such as cilta-cel and ide-cel, involve a lengthy inpatient process that includes preparation with chemotherapy, the infusion itself, and post-treatment observation. Similarly, bsAbs require step-up dosing, which also necessitates hospital stays.  

With these therapies being introduced earlier in treatment plans, hospitals face growing demands for bed space. For example, a single treatment center in Germany projects a need for over 600 inpatient days annually for cilta-cel alone, with costs exceeding €14 million. Nationwide, the financial and logistical burden is even higher, potentially requiring hundreds of additional hospital beds and billions in treatment costs.  

Efforts to reduce inpatient stays include outpatient programs, home monitoring devices, and medications to prevent side effects. While these strategies can help, the increasing use of these advanced therapies underscores the need for expanded hospital resources to ensure safe and effective care for patients with multiple myeloma.

 

 

"Study of Risk Factors for the Occurrence of Infection in Multiple Myeloma: Case-Control Study in Myeloma Patients"

Source

Niang, E.D., Sarr, K., Thiam, A. et al. Study of Risk Factors for the Occurrence of Infection in Multiple Myeloma: Case-Control Study in Myeloma Patients. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-024-01953-1  January 22, 2025. 

Overview

 

Infections are a major concern for patients with multiple myeloma, often leading to severe illness or death. A study at Dalal Jamm Hospital analyzed infection risk factors in myeloma patients treated between 2005 and 2024.  

The study included 108 patients with infections and 80 without, matched by age and sex. The average age was around 61 years, and pulmonary infections (50%) and urinary infections (30%) were the most common. Median survival was 1.2 years for infected patients, compared to 2.6 years for those without infections.  

Key risk factors for infection included:  

• Charlson comorbidity score ≥ 1 (more preexisting conditions increased risk).  
• Positive C-reactive protein (CRP), indicating inflammation.  
• Renal failure, which weakened patients' ability to fight infections.  
• Type of treatment, with some therapies linked to higher infection risks.  

This study highlights the importance of closely monitoring myeloma patients with these risk factors to prevent and manage infections effectively.

 

 

"CM313 Monotherapy in Patients With Relapsed/Refractory Multiple Myeloma or Marginal Zone Lymphoma: A Multicenter, Phase 1 Dose-Escalation and Dose-Expansion Trial"

Source

Zhou, H., Huang, Z., Fang, B., Jing, H., Xia, Z., Song, Y., Cai, Z., An, G., Qin, L., Bao, L., Li, X., Liu, Y., Wang, Y., Li, L. and Chen, W. (2025), CM313 Monotherapy in Patients With Relapsed/Refractory Multiple Myeloma or Marginal Zone Lymphoma: A Multicenter, Phase 1 Dose-Escalation and Dose-Expansion Trial. Am J Hematol. https://doi.org/10.1002/ajh.27573  January 22, 2025. 

Overview

A new treatment option for patients with relapsed and refractory multiple myeloma (RRMM) is showing promise. CM313, an anti-CD38 monoclonal antibody, was recently tested in a first-in-human clinical trial. CD38 is a protein highly expressed on myeloma cells, making it an effective therapeutic target. Unlike existing anti-CD38 treatments, such as daratumumab and isatuximab, CM313 features a unique molecular structure that may offer comparable efficacy with a manageable safety profile.  

The study enrolled 44 patients, including 41 with RRMM who had already undergone a median of three prior treatments. Participants received escalating doses of CM313 to determine safety, followed by further testing of the most effective doses. Side effects were generally mild, with infusion-related reactions reported in about 59% of patients. Other common side effects included low white blood cell and lymphocyte counts. Serious side effects were rare, and no patients discontinued treatment due to toxicity.  

CM313 demonstrated encouraging clinical activity. The overall response rate (ORR) was 36.6%, with 44.4% of patients in the 16 mg/kg group achieving a response. Responses were rapid, occurring in just under a month on average, and durable, lasting a median of 16.4 months. Median progression-free survival (PFS) was 4.3 months, while the 12-month overall survival rate was 80.5%, further supporting its potential as a viable option for heavily pretreated RRMM patients.  

These results suggest that CM313 is both effective and well-tolerated in RRMM. With further research, including an ongoing study to evaluate subcutaneous delivery, CM313 could become an important addition to the treatment landscape for patients with limited options.

 

 

"Anxiety and Depression Among Patients Newly Diagnosed with Lymphoma and Myeloma"

Source

Oreofe O. Odejide, Angel M Cronin, Tamryn F Gray, Tsotso Ablorh, Anna Ying, Amelia Yang, Cheyenne Annette Ashley, Anna Juanjuan Tidswell, Eleanor Shi, Miryam Yusufov, Gregory A. Abel, Lizabeth Roemer; Anxiety and Depression Among Patients Newly Diagnosed with Lymphoma and Myeloma. Blood Adv 2025; bloodadvances.2024014821. doi: https://doi.org/10.1182/bloodadvances.2024014821 January 22, 2025. 

Overview  

A recent survey highlights the significant emotional toll faced by patients diagnosed with lymphoma or myeloma. Conducted between July 2021 and September 2022, the study examined anxiety and depression symptoms in 200 adults within six months of their diagnosis. Over half (56.2%) of participants reported clinically significant anxiety and/or depression, with 52% experiencing anxiety and 27.5% experiencing depression.  

Key factors linked to anxiety included low financial satisfaction and higher levels of medical mistrust. Depression was more likely among those with low financial satisfaction and limited social support. Both conditions had a notable impact on quality of life (QOL), with depression being associated with significantly reduced QOL scores.  

These findings emphasize the need for routine mental health screening and access to psychological support for patients with lymphoma and myeloma. Addressing these issues early could improve emotional well-being and overall quality of life for this vulnerable group.  

 

 

"Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: Results from the prospective, observational CHAGAL study"

Source

Morè, S., Federici, I., Bossi, A., Rupoli, S., Morsia, E., Manieri, V.M., Olivieri, A., Petrucci, M.T., Fazio, F., Lisi, C., Sorella, S., Paoli, A.D., Farina, F., Mele, A., De Francesco, R., Greco, A., Fioritoni, F., Liberatore, C., De Toritto, T.C., Tordi, A., Siniscalchi, A., Brunori, M., Sgherza, N., Musto, P., Amendola, A., Vacca, A., Solimando, A.G., Melaccio, A., Palma, A., Melillo, L.M.A., Ciuffreda, L., Gentili, S., Buda, G., Del Giudice, M.L., Falcone, A.P., Tosi, P., Tomassetti, S., Rotondo, F., Gozzetti, A., Galieni, P., Ruggieri, M., Frigeri, F., Bianco, R., Lombardo, A., Trastulli, F., Corvatta, L., Zizzo, C., Duro, G. and Offidani, M. (2025), Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: Results from the prospective, observational CHAGAL study. HemaSphere, 9: e70079. https://doi.org/10.1002/hem3.70079  January 22, 2025. 

Overview    

Gaucher disease (GD) is a rare genetic disorder caused by a deficiency in the enzyme β-glucocerebrosidase, which leads to the buildup of glucosylceramide in cells, forming "Gaucher cells." Evidence suggests that patients with Type 1 Gaucher disease (GD1) have a significantly higher risk of developing multiple myeloma (MM). However, studies on the overlap between GD1 and MM remain limited.  

A recent multicenter study in Italy aimed to assess the prevalence of undiagnosed GD1 among 1,004 patients with smoldering MM (SMM), newly diagnosed MM (NDMM), or relapsed/refractory MM (RRMM). Blood samples were analyzed for glucocerebrosidase enzyme activity, and genetic testing was performed when abnormalities were detected. The study found that 1.3% of patients had mutations in the GBA1 gene associated with GD1, with one patient diagnosed with GD1, giving a prevalence of 0.09%. This rate was higher than GD1 prevalence in the general population, indicating a strong link between GD1 and MM.  

Interestingly, common GD1 signs, such as thrombocytopenia, splenomegaly, and high ferritin levels, were not consistently observed, making it challenging to create a clear diagnostic algorithm. The study suggests that screening for GD1 using dried blood spot testing should be considered in MM or SMM patients showing signs of GD1, as early detection allows for enzyme replacement therapy (ERT), which could improve outcomes.  

The findings add to growing evidence that GD1 increases the risk of plasma cell disorders like MM and highlight the need for awareness among clinicians to prevent diagnostic delays and optimize care for affected patients.  

 

 

"Minimal Residual Disease Testing Infrastructure in Multiple Myeloma: Guidance for Clinical Trial and Routine Practice Use in Canada"

Source

Hira S Mian, Alissa Visram, Steven Chun-Min Shih, Suzanne Trudel, Annette E Hay, Richard LeBlanc, Michael Sebag, Rayan Kaedbey, Julie Stakiw, Irwindeep Sandhu, Chai W Phua, Philip G Kuruvilla, Ibraheem Othman, Graeme Quest, David McMullen, Gabriele Colasurdo, Rami Kotb, Christopher P Venner, Minimal Residual Disease Testing Infrastructure in Multiple Myeloma: Guidance for Clinical Trial and Routine Practice Use in Canada, Clinical Lymphoma Myeloma and Leukemia, 2025,ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.01.010. January 23, 2025. 

Overview    

Minimal residual disease (MRD) is one of the strongest predictors of progression-free and overall survival in multiple myeloma (MM). Recent recommendations from a working group of Canadian hematologists emphasize the need for MRD testing to become a routine part of MM care across the country. MRD testing provides valuable information about how many cancer cells remain after treatment, helping doctors make informed decisions about future therapies. Achieving MRD negativity, where no cancer cells are detectable, is strongly linked to better patient outcomes.

The working group has outlined several key recommendations to ensure that MRD testing becomes widely accessible and standardized. First, MRD testing should be available to all MM patients, both those eligible for a stem cell transplant and those who are not. The testing should be done using highly sensitive assays that can detect as few as one cancer cell in one million, with a target sensitivity of 10⁻⁶. They recommend that bone marrow samples be collected carefully, with a focus on using the first aspirate to reduce the effects of contamination. Training for healthcare providers on proper sample collection is essential for ensuring high-quality results.

To address capacity issues, the group stresses the need for provincial and regional resources to make MRD testing more accessible across Canada. Currently available assays, such as those based on next-generation flow (NGF), are suitable for routine practice, but there is a call for developing more advanced assays that will be easier to implement nationwide. The working group also recommends saving baseline bone marrow samples for future testing, particularly if next-generation sequencing (NGS) assays are expected to be used in the near future. This requires systems to store and share samples across laboratories, ensuring they are available when needed.

Timing of MRD testing is another important consideration. For patients on maintenance therapy after stem cell transplant, MRD testing could be considered at 24 months, with additional samples taken to confirm sustained MRD negativity. Clinical trials are also encouraged to incorporate standardized MRD testing to ensure consistent results across multiple sites. Given Canada’s vast geography, MRD testing for clinical trials should be regionalized, with at least two centers (one in Western Canada and one in Eastern Canada) using the same standardized assays.

The working group’s recommendations are a significant step toward integrating MRD testing into routine clinical practice for MM in Canada. As new therapies continue to emerge, MRD testing will provide crucial insights into a patient’s disease trajectory, allowing for more tailored treatment plans. With the widespread use of MRD testing, Canada can ensure that more patients benefit from the advancements in MM care, ultimately improving long-term outcomes and quality of life.

 

 

"Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets"

Source

Luz Yurany Moreno Rueda, Hua Wang, Keiko Akagi, Minghao Dang, Amishi Vora, Li Qin, Hans C. Lee, Krina K. Patel, Pei Lin, David E. Mery, Fenghuang Zhan, John D. Shaughnessy, Qing Yi, Yang Song, Bo Jiang, Maura L. Gillison, Sheeba K. Thomas, Donna M. Weber, Lixia Diao, Jing Wang, Isere Kuiatse, Elisabet E. Manasanch, David E. Symer, Robert Z. Orlowski, Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets, Cell Reports Medicine, 2025, 101925, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2024.101925. January 23, 2025. 

Overview    

Researchers have used new techniques like single-cell RNA sequencing (scRNA-seq) combined with single-cell B-cell receptor sequencing (scBCR-seq) to study multiple myeloma (MM) more closely. This approach allows scientists to identify abnormal plasma cells (neoplastic cells) and compare them to normal plasma cells. By using this method, they discovered more genes that are out of balance, especially in patients with early forms of the disease.

The research focused on finding key genes that could drive the disease. They identified two genes—MAD2L1 and MAT2A—that play a role in myeloma and could be targeted by drug-like molecules to stop the growth of myeloma cells in lab tests. Another important finding was the role of a protein called LAMP5, which is found in high amounts on cancerous plasma cells. This protein helps tumors grow and become more aggressive, especially when it interacts with a gene called c-MYC. 

Excitingly, scientists developed a monoclonal antibody that targets LAMP5 on the surface of myeloma cells. This antibody was shown to work well when combined with a drug or used in a special type of immune therapy called CAR T-cell therapy. These discoveries open the door to new treatment options for multiple myeloma, aiming to target the disease more precisely and potentially stop its progression.

 

 

"Combining SKY92 gene expression profiling and FISH (according to R2-ISS) defines ultra-high-risk Multiple Myeloma"

Source

Zhou, X., Hofmann, A., Engel, B., Vogt, C., Nerreter, S., Tamamushi, Y., Schmitt, F., leberzammer, M., Stanojkovska, E., Truger, M., Xiao, X., Riedhammer, C., Steinhardt, M.J., John, M., Mersi, J., Han, S., Munawar, U., Waldschmidt, J.M., Haferlach, C., Einsele, H., Rasche, L. and Kortüm, K.M. (2025), Combining SKY92 gene expression profiling and FISH (according to R2-ISS) defines ultra-high-risk Multiple Myeloma. HemaSphere, 9: e70078. https://doi.org/10.1002/hem3.70078  January 23, 2025. 

Overview    

The definition of high-risk (HR) multiple myeloma (MM) is still being debated, but recent research has made progress in identifying patients with the most aggressive forms of the disease. A study involving 258 MM patients used two key methods—FISH (fluorescence in situ hybridization) and SKY92 gene expression profiling—to better understand and detect HR MM. They found that HR SKY92 was more common in patients with relapsed/refractory (RR) MM (47.1%) compared to those newly diagnosed (ND) (17.9%). Patients with HR SKY92 had shorter progression-free survival (PFS) and overall survival (OS), meaning their disease progressed more quickly and they lived for a shorter period after diagnosis.

When combining SKY92 with FISH, which looks for specific genetic changes, researchers found that only 27.1% of patients were considered HR by both methods—this group, called "double HR," had the worst survival outcomes. This was true for both newly diagnosed and relapsed patients, with "double HR" patients experiencing significantly shorter PFS and OS, especially in relapsed cases.

Finally, whole genome sequencing (WGS) helped uncover specific gene mutations in some patients, including mutations in CRBN, TP53, and TNFRSF17, which may help explain why some patients have a more aggressive form of the disease. This research shows that combining SKY92, FISH, and WGS can better identify patients with ultra-high-risk MM, offering important insights for future treatment and risk assessment.

 

 

"Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction"

Source

Murphy, C.S., Fairfield, H., DeMambro, V.E., Fadel, S., Gartner, C.A., Karam, M., Potts, C., Rodriguez, P., Qiang, Y.-W., Hamidi, H., Guan, X., Vary, C.P.H. and Reagan, M.R. (2025), Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction. Mol Oncol. https://doi.org/10.1002/1878-0261.13794  January 23, 2025. 

Overview    

 One factor linked to the development and progression of mulitple myeloma (MM) is the disruption of fatty acid (FA) metabolism, but how exactly this happens is not well understood. In this study, researchers looked at a group of enzymes called long-chain fatty acid coenzyme A ligases (ACSLs), which are involved in converting fatty acids into a form the body can use for energy. They found that higher levels of ACSL1 and ACSL4 in myeloma cells were linked to worse outcomes for patients.

Further analysis revealed that ACSL3 and ACSL4 were essential for myeloma cells to survive, suggesting they play a key role in the disease. When researchers tested a drug called Triacsin C (TriC) to block ACSLs in myeloma cell lines, it caused the cells to die, slow down their growth, and lose their ability to survive. The treatment also triggered processes like apoptosis (cell death) and stress in the cells. It affected the mitochondria, the powerhouses of the cells, reducing their ability to produce energy and making the cells less able to function.

These findings suggest that targeting ACSLs could be a promising new approach to treat multiple myeloma by disrupting the cancer cells' metabolism and reducing their survival.

 

 

"Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone"

Source

Slørdahl, T.S., Askeland, F.B., Hanssen, M.S.S., Hov, H., Sundt-Hansen, S.M., Lindahl, S., Vethe, N.T., Hjorth-Hansen, H., Fenstad, M.H., Waage, A., Hjertner, Ø., Schjesvold, F. and Sundan, A. (2025), Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone. eJHaem, 6: e1091. https://doi.org/10.1002/jha2.1091 January 23, 2025.  

Overview    

With multiple myeloma, cells produce too much of a protein called monoclonal immunoglobulin. To survive, myeloma cells rely on breaking down proteins efficiently, and current treatments focus on blocking one of the main protein breakdown systems, called the proteasome. However, another protein breakdown system, called autophagy, isn't targeted in myeloma treatment yet. 

In this Phase I trial, researchers tested a combination of two drugs: carfilzomib, a proteasome inhibitor, and hydroxychloroquine, an autophagy inhibitor. The treatment was well tolerated by patients with relapsed or refractory multiple myeloma, meaning it caused mostly mild side effects. The overall response rate was 44%, showing that this combination has potential to effectively treat multiple myeloma. 

This trial is registered on clinicaltrials.gov (# NCT04163107).

 

 

"Total marrow irradiation as part of autologous stem cell transplantation for patients with multiple myeloma"

Source

Zhong, QX., Meng, FY., Chen, HY. et al. Total marrow irradiation as part of autologous stem cell transplantation for patients with multiple myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06219-y  January 24, 2025. 

Overview    

A study evaluated the combination of total marrow irradiation (TMI) and a reduced dose of melphalan as preconditioning for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). The study included 11 patients, aged 46–75 years, with varying risk levels. Before ASCT, patients had responses ranging from stringent complete response (sCR) to progressive disease. Most received melphalan doses of 120–140 mg/m² and TMI at 12 Gy.

After transplantation, 10 out of 11 patients had no minimal residual disease (MRD) in their grafts, and one patient had MRD due to disease progression. The treatment was well tolerated, with mild side effects such as oral and gastrointestinal mucositis. There were no transplant-related deaths or serious complications. After the transplant, most patients who hadn't achieved sCR before treatment progressed to sCR or very good partial response (VGPR). 

After a median follow-up of nearly two years, the progression-free survival (PFS) rate was 90.9%, and overall survival (OS) was 100%. These results suggest that this treatment regimen of melphalan and TMI is both safe and effective for treating MM.

 

 

"Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: an exploratory biomarker study of JCOG1105 (JCOG1105A1)"

Source

Ri, M., Iida, S., Saito, K. et al. Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: an exploratory biomarker study of JCOG1105 (JCOG1105A1). Cancer Chemother Pharmacol 95, 29 (2025). https://doi.org/10.1007/s00280-025-04752-1  January 24, 2025. 

Overview    

A study aimed to identify metabolites in plasma that could predict toxic side effects and treatment responses in multiple myeloma (MM) patients receiving bortezomib (Btz) as part of a treatment regimen. The researchers analyzed plasma samples from 54 transplant-ineligible MM patients enrolled in a clinical trial comparing two less-intensive treatment regimens. They focused on lipid metabolites before starting Btz therapy.

The results showed that high levels of certain phospholipids were linked to more severe peripheral neuropathy (BiPN), a common side effect of Btz. On the other hand, lower levels of specific fatty acids were found in patients who developed severe skin disorders. However, no metabolites were strongly connected to treatment response.

This research suggests that plasma lipid metabolites could potentially be used as biomarkers to predict Btz-related toxicities, such as nerve damage or skin problems, in MM patients before starting Btz treatment.

 

 

"The association between the dietary inflammatory index and multiple myeloma: a case–control study"

Source

Zahedi, H., Jowshan, MR., Rasekhi, H. et al. The association between the dietary inflammatory index and multiple myeloma: a case–control study. Sci Rep 15, 3123 (2025). https://doi.org/10.1038/s41598-025-87494-7  January 24, 2025. 

Overview    

A study explored the connection between the Dietary Inflammatory Index (DII) and multiple myeloma (MM), a type of cancer affecting plasma cells. The DII measures how inflammatory a person's diet is, based on the types of foods they eat. This case-control study involved 149 adults with newly diagnosed MM and 359 healthy individuals. Researchers used a detailed food frequency questionnaire to assess the diets of participants and calculate their DII scores.

The findings showed that people with higher DII scores, which indicate more pro-inflammatory diets, were significantly less likely to have MM compared to those with lower scores. Even after adjusting for factors like age, sex, and body mass index (BMI), the association remained strong. 

This suggests that a diet with more inflammatory foods might increase the risk of developing MM. If these findings are confirmed by future studies, they could help guide personalized diet recommendations for MM patients, especially for healthcare providers and cancer dietitians.

 

 

"Income and education affect prognosis and treatment in symptomatic myeloma"

Source

Larfors, G., Carlson, K., Day, C. et al. Income and education affect prognosis and treatment in symptomatic myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06214-3  January 24, 2025. 

Overview    

A study in Sweden examined how income and education levels affect treatment and survival in multiple myeloma (MM) patients. Even with a publicly funded healthcare system, socioeconomic factors played a significant role in the outcomes. The study analyzed data from over 8,600 MM patients between 2008 and 2021.

The results showed that patients with higher income and education levels had longer survival. Low-income patients had a 40% higher risk of death, and those with lower education had a 30% higher risk. Additionally, patients with higher income were more likely to receive newer and more advanced treatments like lenalidomide and pomalidomide, while low-income patients were less likely to get treatments like stem cell transplants or melphalan tablets.

The findings suggest that even in countries with universal healthcare, socioeconomic status influences treatment access and outcomes. These disparities highlight the need for efforts to provide better treatment to lower-income patients, as improving access could help close the gap in survival rates.

 

 

"Effects of Exercise Training on the Bone Marrow Immune Microenvironment and Minimal Residual Disease in Multiple Myeloma Patients Following First-Line Treatment"

Source

Spiliopoulou, P., Rousakis, P., Panteli, C., Eleutherakis-Papaiakovou, E., Migkou, M., Kanellias, N., Ntanasis-Stathopoulos, I., Malandrakis, P., Theodorakakou, F., Fotiou, D., Terpos, E., Gavriatopoulou, M., Tsitsilonis, O.E., Kastritis, E., Dimopoulos, M.A. and Terzis, G. (2025), Effects of Exercise Training on the Bone Marrow Immune Microenvironment and Minimal Residual Disease in Multiple Myeloma Patients Following First-Line Treatment. Scand J Med Sci Sports, 35: e70020. https://doi.org/10.1111/sms.70020  January 24, 2025. 

Overview    

A study looked at how exercise training affects the bone marrow and immune system in multiple myeloma (MM) patients who completed their initial treatment. Eight patients who did exercise along with standard treatment were compared to eight patients who only received medical treatment. 

The results showed that after 5 months of exercise, the patients who exercised had increased levels of monocytes (a type of white blood cell) in their blood, while the control group did not show any changes. In the bone marrow, the exercise group had an increase in a specific subset of T cells, which are important for immune responses. They also showed a reduction in the ratio of certain T cells that may help control disease spread. 

These findings suggest that exercise can have a positive effect on the bone marrow and immune system in MM patients, possibly helping to control the growth of abnormal cells. This could be a useful addition to standard treatments for improving overall disease control.

 

 

"Is t(11;14) always a standard-risk cytogenetic abnormality? Results from GEM05MENOS65 and GEM2012 PETHEMA/GEM transplantation trials"

Source

David F. Moreno, Albert Oriol, Javier de la Rubia, Miguel T. Hernández, María Belén Iñigo, Luis Palomera, Felipe de Arriba, Yolanda González, Ana Isabel Teruel, Jordi López Pardo, Ana López de la Guía, Antonia Sampol, Rafael Ríos-Tamayo, Anna Sureda, Norma C. Gutiérrez, M. Jose Calasanz, María Luisa Martín Ramos, María Victoria Mateos, Jesús San Miguel, Juan José Lahuerta, Joan Bladé, Laura Rosiñol, Is t(11;14) always a standard-risk cytogenetic abnormality? Results from GEM05MENOS65 and GEM2012 PETHEMA/GEM transplantation trials, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.01.014. January 25, 2025. 

Overview    

The study explored whether the genetic abnormality t(11;14) in multiple myeloma (MM) patients always indicates a "standard-risk" condition, as previously thought. The researchers looked at data from two clinical trials: GEM05MENOS65 and GEM2012 PETHEMA/GEM, which involved patients who received stem cell transplants.

Results showed that while t(11;14) has often been categorized as a standard-risk abnormality, its impact on patient outcomes varies. This suggests that other factors, such as treatment options and disease characteristics, should be considered when evaluating risk for patients with this genetic change. The study challenges the idea that t(11;14) should always be treated as standard-risk and highlights the need for more personalized treatment approaches in multiple myeloma.

 

 

"Elevated LIF and JAK-STAT activation drive severe COVID-19 in myeloma patients receiving the BCMA-CD3 bispecific antibody Elranatamab"

Source

Li, Z., Zhang, F., Jin, X. et al. Elevated LIF and JAK-STAT activation drive severe COVID-19 in myeloma patients receiving the BCMA-CD3 bispecific antibody Elranatamab. J Transl Med 23, 117 (2025). https://doi.org/10.1186/s12967-025-06140-y  January 26, 2025. 

Overview    

Immunotherapy can increase the risk of severe COVID-19 in multiple myeloma (MM) patients. To better understand this, a study examined protein levels in MM patients treated with different therapies: bispecific T-cell engagers (BiTe), anti-CD38 monoclonal antibodies (mAbs), and proteasome inhibitor (PI)-based regimens. 

The results showed that BiTe therapy was linked to a higher incidence of severe COVID-19. Researchers identified several proteins that were more or less expressed in patients treated with BiTe compared to those receiving anti-CD38 mAbs or PI regimens. The analysis revealed that BiTe therapy was associated with changes in immune system activity, particularly involving cytokines and leukocyte movement. A protein called Leukemia inhibitory factor (LIF) was found to play a key role in these changes. 

BiTe therapy increases the risk of severe COVID-19 through an inflammatory response, with LIF and the JAK-STAT pathway being significant contributors. Targeting these pathways may help reduce the severity of COVID-19 in MM patients receiving BiTe therapy.

 

 

"A Bayesian Joint Model of Multiple Nonlinear Longitudinal and Competing Risks Outcomes for Dynamic Prediction in Multiple Myeloma: Joint Estimation and Corrected Two-Stage Approaches"

Source

Alvares, D., Barrett, J.K., Mercier, F., Roumpanis, S., Yiu, S., Castro, F., Schulze, J. and Zhu, Y. (2025), A Bayesian Joint Model of Multiple Nonlinear Longitudinal and Competing Risks Outcomes for Dynamic Prediction in Multiple Myeloma: Joint Estimation and Corrected Two-Stage Approaches. Statistics in Medicine, 44: e10322. https://doi.org/10.1002/sim.10322  January 26, 2025. 

Overview    

Predicting cancer-related outcomes, like disease progression, is challenging in oncology. In multiple myeloma (MM), a cancer of plasma cells, disease progression is linked to changes in biomarkers, such as the amount of M-protein in the blood. This M-protein is secreted by the cancerous plasma cells. To better predict important clinical events, it’s crucial to consider how M-protein levels change over time and how they relate to transitions between treatment lines, which could signal disease progression.

Researchers have developed a new model that combines data from multiple biomarkers, including M-protein, to predict clinical outcomes such as time to death or time to the next treatment line. This model uses two different approaches to make predictions: one that estimates all parameters at once and another that does so in stages to save time. 

The model was tested using data from real-world MM patients in the US and was validated using both approaches. This new method can help doctors predict when significant clinical events may happen, based on a patient’s biomarkers and other health information.

 

 

"Knowledge, attitude and practice towards multiple myeloma among medical staff in Enshi Region"

Source

Zou, L., Li, J., Xiang, H. et al. Knowledge, attitude and practice towards multiple myeloma among medical staff in Enshi Region. Sci Rep 15, 3406 (2025). https://doi.org/10.1038/s41598-025-88079-0  January 27, 2025. 

Overview    

A study conducted in the Enshi Region between September and November 2023 evaluated the knowledge, attitudes, and practices (KAP) of medical staff regarding multiple myeloma (MM). This cancer impacts patients' physical, mental, and emotional well-being, making medical professionals key players in its treatment and prevention.

The study gathered responses from 229 medical staff, mostly female (68.6%) and aged 31–40 years (42.4%). The results showed that while knowledge and attitudes were moderate, practices toward MM were proactive. A positive relationship was found between knowledge and attitude, meaning that better understanding of the disease tended to lead to more positive attitudes. Other factors, like education level, age, and occupation, also influenced KAP scores.

The study’s findings suggest that improving medical staff’s knowledge and attitudes about multiple myeloma could enhance treatment practices. This research points to the need for better training and educational programs for healthcare workers to improve their ability to manage and treat MM.

 

 

"International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma"

Costa, L.J., Banerjee, R., Mian, H. et al. International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-024-02482-6 January 27, 2025. 

Overview    

T-cell redirecting therapies (TCRT), including chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs), have made significant progress in treating multiple myeloma (MM). Several treatments targeting B-cell maturation antigen (BCMA) and GRPC5D are already available, with more in development. As these immunotherapies become more widely available, it is important to understand how one treatment may impact the safety and effectiveness of the next. This helps doctors and patients choose the best combination of therapies. An expert panel from the International Myeloma Working Group reviewed factors affecting the success of immunotherapies and provided recommendations for sequencing treatments to maximize patient outcomes.

 

 

*Visit also the IMF's repository of IMWG Publications.

 

"GDF15-mediated enhancement of the Warburg effect sustains multiple myeloma growth via TGFβ signaling pathway"

Xue, W., Li, Y., Ma, Y. et al. GDF15-mediated enhancement of the Warburg effect sustains multiple myeloma growth via TGFβ signaling pathway. Cancer Metab 13, 3 (2025). https://doi.org/10.1186/s40170-025-00373-7  January 27, 2025. 

Overview    

The Warburg effect, where cells shift to a type of metabolism called aerobic glycolysis, is linked to the growth of tumors like multiple myeloma (MM). However, the exact mechanisms behind this process in MM were not fully understood. This study found that growth differentiation factor 15 (GDF15) is a key regulator of glycolysis in MM. GDF15 is highly expressed in MM cells and patient samples, and it helps MM cells grow by promoting cell division and preventing cell death. GDF15 also boosts the Warburg effect in MM cells, increasing glucose use, lactate production, and decreasing normal energy production. It does this by activating the TGFβ signaling pathway, which leads to the expression of a gene that transports glucose into cells. When the TGFβ pathway was blocked, the cancer-promoting effects of GDF15 were reduced. Experiments in mice showed that lowering GDF15 reduced tumor growth, while increasing GDF15 made tumors grow faster. This study suggests that targeting the GDF15-TGFβ pathway could offer a new way to treat MM in the future.

 

 

"Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study)"

Glöckner, A., Schönland, S., Einsele, H. et al. Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study). BMC Cancer 25, 147 (2025). https://doi.org/10.1186/s12885-025-13503-7  January 27, 2025.  

Overview    

While treatments for multiple myeloma have improved, many patients still experience relapse or disease progression. After high-dose chemotherapy with autologous stem cell transplant, patients with relapsed myeloma can live for 2–3 more years, depending on factors like how long they stayed in remission. Recently, allogeneic stem cell transplant (using stem cells from a donor) has shown promise as a treatment for patients whose myeloma has relapsed or progressed. However, there are no large, randomized trials yet to confirm its effectiveness as a second-line therapy for multiple myeloma, and such studies are needed to fully understand its potential benefits.