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 March 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 March 2025)

"Exploration of the Prognostic Markers of Multiple Myeloma Based on Cuproptosis-Related Genes"

Source

Gao, X.-H., Yuan, J., Zhang, X.-X., Wang, R.-C., Yang, J., Li, Y. and Li, J. (2025), Exploration of the Prognostic Markers of Multiple Myeloma Based on Cuproptosis-Related Genes. Cancer Reports, 8: e70151. https://doi.org/10.1002/cnr2.70151  March 5, 2025.  

Overview

In multiple myeloma, Velcade® (bortezomib) is a key treatment. Yet, some MM cells become resistant to it, reducing its effectiveness. This study found that a protein called Kruppel-like factor 2 (KLF2) is linked to bortezomib resistance. MM cells that were resistant to BTZ had higher levels of KLF2, and reducing KLF2 made these cells grow more slowly, undergo more cell death, and become more sensitive to bortezomib

Further investigation showed that another protein, USP4, helps stabilize KLF2 by preventing its breakdown. This, in turn, promotes cell survival and drug resistance. KLF2 also regulates the activity of HMGA2, a protein that influences cell growth and survival, creating another layer of resistance. USP4 affects HMGA2 levels through KLF2, forming a chain reaction that contributes to bortezomib resistance.

These findings highlight the importance of the USP4/KLF2/HMGA2 pathway in MM drug resistance. Targeting these proteins could offer new strategies to overcome BTZ resistance and improve treatment outcomes for MM patients.

 

 

"BCMA-targeted therapies for multiple myeloma: latest updates from 2024 ASH annual meeting"

Source

Zheng, H., Xian, H., Zhang, W. et al. BCMA-targeted therapies for multiple myeloma: latest updates from 2024 ASH annual meeting. J Hematol Oncol 18, 23 (2025). https://doi.org/10.1186/s13045-025-01675-5   March 1, 2025

Overview

B-cell maturation antigen (BCMA) is a key target in multiple myeloma (MM) treatment, with antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and CAR-T cell therapies showing promising results. At the 2024 ASH Annual Meeting, researchers shared the latest findings on these therapies, highlighting their impact on both relapsed/refractory MM (R/RMM) and newly diagnosed MM (NDMM).  

Blenrep, or Belantamab mafodotin (belamaf), the first BCMA-targeted ADC, was initially withdrawn from the U.S. market but is showing potential for a comeback. Recent trials, such as DREAMM-7 and DREAMM-8, demonstrated that belamaf-based combinations significantly extended progression-free survival (PFS) and improved response rates. The DREAMM-9 trial also showed high response rates in transplant-ineligible NDMM patients treated with belamaf plus standard therapy. Meanwhile, Tecvyali^™ (teclistamab), an FDA-approved BsAb targeting BCMA and CD3, continues to show strong efficacy and manageable side effects. Data from the MajesTEC-2 and TRIMM-2 studies revealed high response rates in R/RMM patients, with minimal cases of severe side effects like cytokine release syndrome (CRS) or neurotoxicity. Additionally, MajesTEC-4 and MajesTEC-5 trials demonstrated that teclistamab, alone or in combination, is effective as maintenance therapy after stem cell transplant in NDMM patients.  

CAR-T therapy remains a powerful option for MM. The CARTITUDE-4 trial showed that Carvykti^® (ciltacabtagene autoleucel, or cilta-cel) led to significantly higher MRD-negative rates compared to standard treatments. Another promising CAR-T therapy, anitocabtagene autoleucel (anito-cel), demonstrated a 100% overall response rate in early-phase trials, with most patients achieving deep remission. These findings highlight the growing potential of BCMA-targeted therapies in MM. As research continues, these treatments may further improve outcomes for both newly diagnosed and relapsed patients.

 

 

"On behalf of GBRAM, Phase 2 trial of daratumumab, cyclophosphamide, thalidomide and dexamethasone in newly diagnosed multiple myeloma"

Source

Andrade Santos, Herbert Henrique de Melo Santos, Allan de Souza Santos, Larissa Ferreira Lucas, Cristiane Almeida Requião de Pinna, Paula Nogueira Caldas Freire, Adriano Araujo de Jesus, Alessandro de Moura Almeida, Daniela Dourado Dutra, Marcos Fonseca Chaves, Jamile Souza Nicanor, Marco Aurelio Salvino, Maria da Gloria Bomfim Arruda, Vania Hungria; on behalf of GBRAM, Phase 2 trial of daratumumab, cyclophosphamide, thalidomide and dexamethasone in newly diagnosed multiple myeloma. Blood Neoplasia 2025; 100081. doi: https://doi.org/10.1016/j.bneo.2025.100081  March 3, 2025.

Overview

A new study tested a treatment combination for newly diagnosed multiple myeloma (NDMM) in patients eligible for a stem cell transplant. The regimen included daratumumab (Dara), cyclophosphamide, thalidomide, and dexamethasone (Dara-CTD). Patients received four cycles of this combination before a transplant, followed by additional treatment with daratumumab, thalidomide, and dexamethasone, and then daratumumab alone as maintenance therapy.

Among the 24 patients in the study (average age 59.5 years), 75% achieved a very good partial response (VGPR) or better after treatment. At three years, 65% had not experienced disease progression, and the four-year overall survival rate was 70%. The most common side effects included constipation, low white blood cell counts, nerve pain, and mouth sores. There were seven cases of COVID-19, with two resulting in death. Two patients stopped treatment due to side effects.

This PI-free regimen (which does not include proteasome inhibitors) showed promising effectiveness with manageable side effects in transplant-eligible NDMM patients.

 

 

"CKS2 Silencing Affects Proliferation and Apoptosis in Multiple Myeloma through the PTEN/ AKT/mTOR Pathway"

Source

Zi-Zi J, Wei Y, Jia-Lin T, Xiao-Bin Z, Jian-Bin C. CKS2 Silencing Affects Proliferation and Apoptosis in Multiple Myeloma through the PTEN/ AKT/mTOR Pathway. J Cancer. 2025 Mar 3;16(6):1987-2000. doi: 10.7150/jca.106190. PMID: 40092696; PMCID: PMC11905417.  March 3, 2025. .

Overview

Multiple myeloma (MM) affects plasma cells. Researchers are still working to understand the molecular changes that drive the disease. A new study found that a protein called CKS2 is highly active in myeloma cells and may play a key role in tumor growth.  

By studying patient samples and lab-grown myeloma cells, scientists discovered that reducing CKS2 levels slowed cancer cell growth and increased cell death, while higher CKS2 levels had the opposite effect. Further analysis showed that CKS2 influences the PTEN/AKT/mTOR pathway, which helps regulate cell survival. The study also identified a direct interaction between CKS2 and thioredoxin (TXN), a protein that may help stabilize CKS2.  

These findings suggest that targeting CKS2 could be a new strategy for treating multiple myeloma. More research is needed to explore its potential as a therapy.

 

 

"Semi-Automated Interphase FISH (iFISH) Spot Scoring in CD138-Positive Cells: Validation Study for Genetic Abnormalities Detection in Multiple Myeloma"

Source

Borri, D., Lin, C.J., Camillo, V., Kishimoto, R.K., Santos, M.F.M., Safranauskas, R.M., Cordeiro, M.G., Silva, J.d.L., Coimbra, A.A.C., Silva, G.d.S.E., Cervato, M.C. and Velloso, E.D.R.P. (2025), Semi-Automated Interphase FISH (iFISH) Spot Scoring in CD138-Positive Cells: Validation Study for Genetic Abnormalities Detection in Multiple Myeloma. Microsc Res Tech. https://doi.org/10.1002/jemt.24844  March 3, 2025

Overview

Researchers tested an automated method for analyzing FISH (Fluorescent in Situ Hybridization) results in multiple myeloma patients. FISH is used to detect genetic changes in cancer cells. The study compared manual, automated, and semi-automated scoring methods across 180 patient samples, using six genetic probes.

The results showed that fully automated scoring was not reliable, but semi-automated scoring (automated with manual review) was highly accurate and time-efficient, especially for detecting gene deletions and gains. These findings suggest that semi-automated FISH analysis could improve efficiency in cytogenetics labs and may become a standard practice for multiple myeloma testing.

 

 

"Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis"

Source

Fotiou D, Theodorakakou F, Solia E, Spiliopoulou V, Ntanasis-Stathopoulos I, Malandrakis P, Psimenou E, Kanellias N, Roussou M, Migkou M, Eleutherakis-Papaiakovou E, Andrikopoulou A, Giannouli S, Gavriatopoulou M, Terpos E, Kastritis E, Dimopoulos MA. Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis. Clin Lymphoma Myeloma Leuk. 2025 Mar 4:S2152-2650(25)00079-5. doi: 10.1016/j.clml.2025.03.003. Epub ahead of print.  March 4, 2025. 

Overview

Renal impairment (RI) is a common and serious complication in newly diagnosed multiple myeloma (NDMM), with some patients requiring dialysis. A new study looked at 73 NDMM patients who needed dialysis between 2010 and 2023 to understand how treatment affects their kidney function and survival.

All patients were treated with bortezomib-based therapies, and after a median follow-up of about 3 years, 42.5% of patients became independent from dialysis. These patients had better survival (36 months vs. 13.3 months) and lower early mortality. Factors that helped patients become independent from dialysis included younger age, hypercalcemia, and a good early response to treatment.

The study also found that patients with high-risk genetic features had worse outcomes, and those who achieved a deep response to treatment (such as at least a very good partial response) had better chances of kidney recovery. The results suggest that while dialysis independence is possible for some patients, outcomes are still poor for those who remain on dialysis. Further research into more aggressive treatments, like quadruplet regimens with anti-CD38 antibodies, is needed to improve outcomes for these patients.

 

 

"Survival, years of life lost and attrition rates in multiple myeloma patients in France"

Source

A. Perrot, F. Raguideau, H. Denis, M. Prodel, M. Javelot, M. Pierres, C. Touzeau, Survival, years of life lost and attrition rates in multiple myeloma patients in France, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.03.004. March 4, 2025. 

Overview

A new study analyzed real-world data from 33,032 multiple myeloma (MM) patients in France to better understand their characteristics, survival rates, and treatment outcomes. The patients started their treatment between 2014 and 2021 and were followed until 2021.

The study found that the 5-year overall survival (OS) rate for MM patients was 51.9%. For patients who had a stem cell transplant (L1T), the survival rate was much higher at 78.3%, compared to 43.6% for those who did not have the transplant (L1NT).

The study also showed that MM patients lost an average of 12.3 years of life compared to the general population, with those who had a transplant losing 17 years and those without a transplant losing 11 years.

Attrition rates (patients not receiving at least 2 lines of treatment) were high, with 38% of patients missing this treatment. Patients who did not receive a transplant had a higher attrition rate (41%) compared to those who did (29%).

The study highlights the importance of providing personalized and effective treatments for all MM patients, whether or not they receive a stem cell transplant. Further research will be needed to evaluate the impact of newer treatments on MM patients in real-life settings

 

 

"Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives"

Source

Oxana Lungu, Denise Toscani, Nicola Giuliani, Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives, Journal of Bone Oncology, 2025, 100668, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2025.100668. March 4, 2025. 

Overview

Multiple myeloma (MM) may cause severe bone damage, leading to pain and other bone-related issues. This review explains the complex interactions between cancer cells and the bone marrow that drive bone destruction in MM.

The study focuses on osteoclasts (OC), cells that break down bone, and osteoblasts (OB), cells that build bone, along with other bone cells. It also discusses how immune cells and the bone marrow environment work together to influence the disease.

Additionally, the review highlights the molecular signaling pathways and inflammatory cytokines that contribute to bone damage. Changes in the metabolism of the bone marrow also play a role.

Finally, the review looks at new treatment strategies that target these pathways to protect bones and improve outcomes for MM patients. Understanding these mechanisms is key to developing better treatments to prevent bone damage in MM.

 

 

"Dexamethasone for the management of CRS Related to teclistamab in patients with relapsed/refractory multiple myeloma"

Source

Davis, J.A., Snyder, J., Rice, M. et al. Dexamethasone for the management of CRS Related to teclistamab in patients with relapsed/refractory multiple myeloma. Blood Cancer J. 15, 32 (2025). https://doi.org/10.1038/s41408-025-01222-y  March 4, 2025.  

Overview

Cytokine Release Syndrome (CRS) is a common side effect in patients receiving immune therapies like teclistamab, which is used to treat relapsed/refractory multiple myeloma (RRMM). CRS occurs when T-cells are activated, causing symptoms like fever, low blood pressure, and difficulty breathing. If not treated, CRS can be life-threatening.

This study looked at how dexamethasone (a corticosteroid) and tocilizumab (an anti-inflammatory medication) are used to manage CRS in patients treated with teclistamab. The study involved 243 patients from six US academic centers. It found that 55% of patients experienced CRS, but most cases were mild (grade 1). Severe CRS (grade 3 or higher) was rare and could be managed with medication.

The study showed that dexamethasone alone was effective for treating grade 1 CRS, and some patients with recurring CRS were treated with additional doses of dexamethasone. This suggests that dexamethasone could be a safe and cost-effective alternative to tocilizumab, especially for patients with mild CRS. By using dexamethasone, healthcare providers may be able to manage CRS in an outpatient setting, which can reduce hospital visits and healthcare costs.

The findings suggest that dexamethasone could be used effectively in managing mild CRS in teclistamab-treated patients, potentially improving the outpatient management of this therapy and reducing treatment costs. However, more research is needed to confirm these results and understand how different disease characteristics might affect treatment outcomes.

 

 

"PMEPA1 Binds NEDD4L to Inhibit the Malignant Progression of Multiple Myeloma by Inactivating Wnt/β-Catenin Signaling"

Source

Hu, S., Gao, X., Zhu, Y. et al. PMEPA1 Binds NEDD4L to Inhibit the Malignant Progression of Multiple Myeloma by Inactivating Wnt/β-Catenin Signaling. Cell Biochem Biophys (2025). https://doi.org/10.1007/s12013-025-01674-w  March 4, 2025.   

Overview

MEPA1 is a protein that has been linked to better survival in multiple myeloma (MM) patients, but its exact role in MM is not fully understood. Researchers studied the relationship between PMEPA1 and NEDD4L, another protein, in MM cells.

The study found that PMEPA1 and NEDD4L were present at low levels in MM cells. When PMEPA1 was increased in MM cells, it slowed down cell growth, caused cell cycle arrest, and promoted cell death (apoptosis). Additionally, PMEPA1 was shown to bind to NEDD4L, which then increased NEDD4L levels in the cells. When NEDD4L was removed, it reduced the effects of PMEPA1 on cell growth, cycle distribution, and apoptosis.

The study also found that PMEPA1 lowered the expression of key proteins involved in cell growth and survival, such as β-catenin, c-Myc, and cyclin D1. However, this effect was blocked when NEDD4L was silenced. When the Wnt/β-catenin pathway was activated using LiCl, the MM cells became more aggressive, suggesting that PMEPA1 works by inhibiting this pathway.

PMEPA1 may help slow down the progression of MM by binding to NEDD4L and deactivating the Wnt/β-catenin signaling pathway. This could provide a new target for future treatments of MM.

 

 

"Implications of lymphocyte kinetics after chimeric antigen receptor T cell therapy for multiple myeloma"

Source

Dingli, S., Rothweiler, P., Binder, M. et al. Implications of lymphocyte kinetics after chimeric antigen receptor T cell therapy for multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02547-0  March 5, 2025.    

Overview

Chimeric antigen receptor T-cell therapy (CAR-T) has significantly improved treatment outcomes for patients with relapsed and refractory multiple myeloma (RRMM). Two CAR-T therapies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel), are FDA-approved and have shown rapid, deep responses, improving survival rates. These therapies require chemotherapy to lower lymphocyte levels before infusion, which is followed by a temporary increase in lymphocyte counts.

In this study, researchers analyzed 134 patients (61 treated with Ide-cel and 73 with Cilta-cel) to examine how lymphocyte recovery after CAR-T infusion affected short- and long-term outcomes. The study found that higher lymphocyte counts in the first few weeks after CAR-T infusion were associated with better outcomes, including progression-free survival (PFS) and overall survival (OS).

Key findings include:

• Lymphocyte counts peaked around day 14 after CAR-T therapy, with Cilta-cel showing faster lymphocyte recovery than Ide-cel.
• A higher peak lymphocyte count (Lmax) in the first two weeks was linked to better PFS and OS.
• Patients with a lymphocyte count greater than 1×10^9/L within the first two weeks had significantly better survival outcomes.
• The study showed that Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) both led to deep responses, with more patients achieving minimal residual disease (MRD) negativity after treatment with Cilta-cel.

Lymphocyte recovery within the first two weeks after CAR-T therapy is crucial for improving patient outcomes. Monitoring lymphocyte counts during this time may help predict the success of treatment, offering a potential strategy for optimizing therapy in RRMM patients.

 

 

"Role of Chimeric Antigen Receptor T-Cells in the Evolving Therapeutic Landscape of Multiple Myeloma: A Literature Review"

Source

Radhi M, Yusuf D A, AlSaffar G M, et al. (March 05, 2025) Role of Chimeric Antigen Receptor T-Cells in the Evolving Therapeutic Landscape of Multiple Myeloma: A Literature Review. Cureus 17(3): e80068. doi:10.7759/cureus.80068  March 5, 2025.     

Overview

For multiple myeloma (MM) patients, chimeric antigen receptor T-cell (CAR-T) therapy is a newer treatment that shows promise. This is especially the case in patients who have already tried multiple other therapies. This review explores how CAR-T therapy works, its effectiveness, and its safety profile. Researchers analyzed studies from multiple medical databases, selecting high-quality clinical trials and observational studies.

MM is the most common primary bone cancer and is more prevalent in African Americans, with diagnosis typically occurring between ages 40 and 70. Although MM is still considered incurable, CAR-T therapy has shown encouraging results in patients who have exhausted other treatment options. However, more research is needed to understand its long-term effects and cost-effectiveness.

Future studies should focus on identifying possible risk factors for MM, such as radiation exposure and infections. Additionally, researchers need to compare CAR-T therapy directly to existing treatments to determine its true benefits, safety, and long-term impact. The effectiveness of CAR-T may also vary based on specific tumor markers, like BCMA expression, which could lead to more personalized treatment strategies.

While CAR-T therapy is currently used for patients who have undergone multiple prior treatments, early evidence suggests it might be more effective if used earlier in the treatment process. More clinical trials are needed to explore this possibility, as well as to develop combination therapies that could reduce side effects.

CAR-T therapy is an exciting new option for MM patients with limited treatment choices. However, challenges like high costs, complex manufacturing, and potential side effects need to be addressed through further research to maximize its benefits for more patients.

 

 

"Impact of Genetic Polymorphisms on Treatment Outcomes of Proteasome Inhibitors and Immunomodulatory Drugs in Multiple Myeloma"

Source

Karimi, F., Aghaei, M. & Saki, N. Impact of Genetic Polymorphisms on Treatment Outcomes of Proteasome Inhibitors and Immunomodulatory Drugs in Multiple Myeloma. Curr. Treat. Options in Oncol. (2025). https://doi.org/10.1007/s11864-025-01295-8  March 5, 2025.     

Overview

One reason treatment outcomes vary in multiple myeloma (MM) is due to genetic differences, known as polymorphisms, which can affect how a patient responds to medication.

Studies show that certain genetic variations related to drug metabolism, DNA repair, inflammation, and cell death may help predict how well a treatment will work. This research suggests that genetic profiling could be used to personalize treatment, making it more effective while reducing side effects.

Although MM treatments have improved, more research is needed to fully understand the biological factors that influence treatment success. By studying genetic differences, scientists may find better ways to predict drug effectiveness and resistance, leading to more tailored and efficient therapies for MM patients

 

 

"Third-line multiple myeloma treatment of inpatients in a German cancer center: analysis of potential cost savings due to decreased renal insufficiency"

Source

Jakobs, F., Ahmadi, P., Osterkamp, V. et al. Third-line multiple myeloma treatment of inpatients in a German cancer center: analysis of potential cost savings due to decreased renal insufficiency. Cost Eff Resour Alloc 23, 6 (2025). https://doi.org/10.1186/s12962-024-00600-w  March 5, 2025    

Overview

Kidney problems are a common complication for people with multiple myeloma (MM), and research suggests that the drug isatuximab may help protect kidney function in these patients. This study examined whether preventing kidney damage with isatuximab could also reduce healthcare costs.

Researchers analyzed hospital records from University Hospital Cologne, Germany, focusing on MM patients treated between 2016 and 2020. They evaluated the financial impact of improved kidney function on hospital costs using Germany’s Diagnosis-Related Group (G-DRG) payment system.

Among the 74 hospital cases reviewed, most (86.5%) fell under a payment category for lymphoma and leukemia. The study found that improving kidney function—specifically reducing severe kidney failure (stage 3) to a milder form (stage 2)—could lead to cost savings of €3,101 to €4,642 per patient.

This study is the first to quantify the economic benefits of isatuximab’s kidney-protective effects in Germany’s healthcare system. By reducing the severity of kidney disease in MM patients, isatuximab could help lower hospital costs while improving patient outcomes.

 

 

"The mitochondrial protease ClpP is a promising target for multiple myeloma treatment"

Source

Xiang Liu, Jinlong Gu, Song Liu, Jingcao Huang, Linfeng Li, Fangfang Wang, Siyao He, Ziyue Mi, Yue Zhang, Jingjing Wen, Qianwen Gao, Haonan Yang, Yu Feng, Hongmei Luo, Xinyu Zhai, Li Zhang, Yuhuan Zheng, Youfu Luo, Ting Niu, The mitochondrial protease ClpP is a promising target for multiple myeloma treatment, Biochemical Pharmacology, 2025, 116855, ISSN 0006-2952, https://doi.org/10.1016/j.bcp.2025.116855.  March 5, 2025.   

Overview

Drug resistance and relapse are major challenges in treating multiple myeloma (MM), making it essential to find new treatment options. A recent study explored a potential new drug, called 7b, which targets a mitochondrial enzyme known as caseinolytic protease P (ClpP).

Researchers found that ClpP levels were higher in MM patients, especially in those with relapsed disease. After testing different ClpP-targeting compounds, they identified 7b as the most effective at killing MM cells in the lab. The drug works by overactivating ClpP, causing mitochondria—the cell’s energy factories—to break down. This leads to a loss of energy production and an increase in toxic molecules, ultimately triggering MM cell death.

Importantly, 7b was effective against MM cells that were resistant to common treatments like bortezomib and lenalidomide. In animal models, the drug also reduced MM tumor growth while causing minimal side effects.

These findings suggest that targeting ClpP with drugs like 7b could be a promising approach for treating relapsed and drug-resistant MM. Further studies are needed to confirm its safety and effectiveness in humans.

 

 

"De novo abnormalities identified by fluorescence in situ hybridization during follow-up confer poor prognosis in Chinese multiple myeloma"

Source

Chen S, Gao L, Feng L, Wang Z, Li Y, Liu Q, Song W, Kong S, Liu Y, Lu J, Chang Y, Huang X, Lai Y. De novo abnormalities identified by fluorescence in situ hybridization during follow-up confer poor prognosis in Chinese multiple myeloma. Front Med (Lausanne). 2025 Mar 5;12:1536825. doi: 10.3389/fmed.2025.1536825.  March 5, 2025.   

Overview

Researchers are emphasizing the importance of regular genetic testing in multiple myeloma (MM) patients to track changes in their disease. A recent study in Chinese MM patients found that new genetic abnormalities (de novo FISH abnormalities) appear over time and are linked to worse outcomes.

In a group of 100 patients, nearly half (49 patients) developed new genetic changes during follow-up. These changes were associated with faster disease progression and shorter survival. Patients who acquired two or more new abnormalities had an even higher risk of relapse. Those who developed these abnormalities within 31 months of diagnosis had significantly worse survival outcomes than those who developed them later.

Additionally, patients with two or more high-risk genetic abnormalities, such as gain of 1q21, deletion of 17p, or specific chromosomal translocations (t(4;14) and t(14;16)), had shorter survival times compared to those without these changes.

This study highlights the need for ongoing genetic testing in MM patients to identify new risk factors early. Detecting these changes could help doctors adjust treatment plans before the disease worsens, potentially improving patient outcomes.

 

 

"Exploration of the Prognostic Markers of Multiple Myeloma Based on Cuproptosis-Related Genes"

Source

Gao, X.-H., Yuan, J., Zhang, X.-X., Wang, R.-C., Yang, J., Li, Y. and Li, J. (2025), Exploration of the Prognostic Markers of Multiple Myeloma Based on Cuproptosis-Related Genes. Cancer Reports, 8: e70151. https://doi.org/10.1002/cnr2.70151  March 5, 2025. .   

Overview

Researchers are exploring a new biological process called cuproptosis and its role in multiple myeloma (MM). This study aimed to identify specific cuproptosis-related genes (CRGs) that could help predict patient outcomes.

By analyzing genetic data, researchers identified 59 key genes linked to cuproptosis in MM. Among them, six biomarkers (PARP1, EDEM3, SEC23A, RSL24D1, TTC37, and SRP72) were strongly associated with disease progression and patient survival. Using these biomarkers, the team developed a prognostic model to help predict outcomes more accurately.

This model was tested and validated using multiple patient datasets. Researchers found that risk score, age, albumin levels, disease stage (ISS score), and β2-microglobulin (B2M) were independent predictors of MM prognosis.

These findings suggest that cuproptosis-related biomarkers could be useful for personalizing MM treatment, helping doctors identify high-risk patients and tailor therapies accordingly.

 

 

"Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions"

Source

Wang H, Zhang J, Ren H, Chen L, Ren J, Liu C, Wu H, Zhou L. Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions. Front Oncol. 2025 Mar 5;15:1531928. doi: 10.3389/fonc.2025.1531928.  March 5, 2025.    

Overview

Multiple myeloma (MM) relies on changes in lipid metabolism—how cells process fats—to grow, survive, and resist treatment. In the low-oxygen environment of the bone marrow, MM cells reprogram their metabolism, altering fat production, storage, and breakdown to meet their energy demands. These changes not only fuel tumor growth but also affect the tumor microenvironment (TME), weakening the immune response and making the cancer harder to treat. Researchers have identified key metabolic shifts, including disruptions in fat uptake, lipid trafficking, and energy production, all of which contribute to disease progression.

Targeting lipid metabolism is emerging as a promising approach to treating MM. Experimental therapies aim to block fat production, enhance fat breakdown, or disrupt fat-related signaling pathways. In addition, combining anti-angiogenic therapy (which limits the cancer’s blood supply) with immunotherapy may help reshape the immune environment, making treatments like anti-PD-1 or anti-BCMA more effective. Blocking VEGF (a factor that promotes blood vessel growth) and the HGF/MET pathway (which supports tumor survival) has shown potential in slowing MM progression and improving treatment response.

While these approaches offer hope, challenges remain. The complexity of lipid metabolism and its interactions with the TME make it difficult to develop highly selective treatments. Future research will focus on combining lipid-targeted therapies with immunotherapy and personalized medicine to improve outcomes. By better understanding how MM cells use fats to survive, scientists may uncover new ways to overcome drug resistance and create long-term, effective treatment strategies for patients.

 

 

"Chimeric antigen receptor T cell therapy based on stem cell-like memory T cells enhances anti-tumour effects in multiple myeloma"

Source

Liu, Z., Xu, X., Wang, Y., Cao, P., Song, J., Ding, K., Liu, H. and Fu, R. (2025), Chimeric antigen receptor T cell therapy based on stem cell-like memory T cells enhances anti-tumour effects in multiple myeloma. Clin. Transl. Med., 15: e70264. https://doi.org/10.1002/ctm2.70264  March 5, 2025. 

Overview

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of multiple myeloma (MM), helping patients live longer. However, many still face relapse and drug resistance. Researchers are now exploring a promising solution: stem cell-like memory T cells (TSCM), a rare type of long-lived immune cell with strong anti-tumor abilities. While TSCM cells are scarce, scientists have found a way to increase their numbers and enhance their function using specific treatments.

In this study, researchers analyzed bone marrow samples from MM patients and found that TSCM cells were significantly lower in newly diagnosed patients compared to healthy individuals or those in remission. By using interleukin-2 (IL-2) and a MEK1/2 inhibitor (MEKi), they successfully expanded TSCM cells in the lab. These enhanced cells showed increased tumor-killing potential, producing higher levels of Perforin and Granzyme B, proteins that help destroy cancer cells. When tested in lab models, the improved TSCM cells demonstrated stronger and longer-lasting anti-myeloma effects than standard CAR-T therapy.

Animal studies further confirmed the benefits of CAR-TSCM therapy, showing a more significant and durable reduction in tumor growth compared to conventional CAR-T. The findings suggest that CAR-TSCM could be a powerful new treatment strategy, potentially leading to deeper and longer-lasting remissions for MM patients. While further research is needed, this approach may offer new hope in overcoming CAR-T resistance and improving long-term outcomes.

 

 

"Accelerating Myeloma Drug Development: Will Minimal Residual Disease Replace Progression-Free Survival as an Intermediate Surrogate End Point?"

Source

María-Victoria Mateos et al., Accelerating Myeloma Drug Development: Will Minimal Residual Disease Replace Progression-Free Survival as an Intermediate Surrogate End Point?. JCO 0, JCO-25-00048 DOI:10.1200/JCO-25-00048  March 6, 2025. 

Overview

A recent study by Shi et al. supports using minimal residual disease (MRD) testing to speed up drug approvals for multiple myeloma (MM). MRD testing detects tiny amounts of cancer left after treatment, and patients who achieve MRD negativity—meaning no cancer is found—tend to have longer remission and survival times. Traditionally, drug effectiveness is measured by tracking how long patients live without disease progression (progression-free survival, PFS) and overall survival (OS), but these measures take years to evaluate. This study suggests that MRD negativity in patients who have achieved a complete response (CR) could serve as a faster way to assess treatment success.  

The researchers found that MRD negativity is a strong predictor of survival in both newly diagnosed and relapsed MM patients. They recommend testing for MRD 9 to 12 months after starting treatment and using highly sensitive methods like next-generation sequencing (NGS) or next-generation flow (NGF). While both methods are effective, only NGS is currently FDA-approved. The findings were significant enough that, in April 2024, the FDA accepted MRD as a new measure for accelerated drug approvals. This decision could help bring new MM treatments to patients faster, and other regulatory agencies may follow suit.  

For patients, the adoption of MRD testing could lead to more personalized care. Those who achieve sustained MRD negativity may be able to reduce or stop certain treatments without increasing their risk of relapse. However, MRD testing currently relies on bone marrow biopsies, which are invasive and painful. Researchers are exploring less invasive blood-based tests that could make MRD monitoring easier and more accessible.  

With MRD now recognized as an important marker of treatment success, clinical trials will continue to refine how it is used. This shift could transform MM treatment by allowing doctors to make faster, more precise decisions, ultimately improving outcomes and quality of life for patients.

 

 

"Associations of ANGPT2 expression and its variants (rs1868554 and rs7825407) with multiple myeloma risk and outcome"

Source

Popek-Marciniec S, Styk W, Chocholska S, Szudy-Szczyrek A, Sidor K, Swiderska-Kolacz G, Hus M, Czerwik-Marcinkowska J, Zmorzynski S. Associations of ANGPT2 expression and its variants (rs1868554 and rs7825407) with multiple myeloma risk and outcome. Front Oncol. 2025 Mar 6;15:1468373. doi: 10.3389/fonc.2025.1468373. March 6, 2025. 

Overview

A new study highlights the role of the ANGPT2 gene in multiple myeloma (MM) and how its genetic variations may influence disease risk and treatment response. ANGPT2 produces angiopoietin-2, a protein that promotes the growth of new blood vessels, a process called angiogenesis, which helps MM tumors grow. Researchers examined two specific genetic variants (rs1868554 and rs7825407) in the ANGPT2 gene to understand their impact on MM development and response to treatment with bortezomib or thalidomide-based therapies.  

The study analyzed DNA from 103 newly diagnosed MM patients and 120 healthy individuals. The results showed that people with the AA genotype of rs1868554 or the CC genotype of rs7825407 had a significantly higher risk of developing MM. However, these genetic variants did not seem to impact ANGPT2 gene activity at the mRNA level. Interestingly, higher ANGPT2 levels in MM patients were linked to higher C-reactive protein (CRP), a marker of inflammation and poor prognosis, and lower lactate dehydrogenase (LDH), which is often associated with disease activity.  

The findings suggest that angiopoietin-2, along with VEGF and HB-EGF, may serve as important markers of angiogenesis in MM. Since blood vessel growth plays a key role in MM progression, targeting angiogenesis-related proteins like ANGPT2 could be a potential strategy for future treatments. Further research is needed to explore how these genetic variations and protein levels might influence MM outcomes and guide more personalized treatment approaches.

 

 

"Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma"

Source

PJia Liu, Zilu Zhang, Wenbin Xu, Mingyuan Jia, Xinyi Zeng, Chengyu Wu, Ze Fu, Xiaoguang Xu, Chenjing Ye, Chao Wu, Hanzhang Xu, Hu Lei, Ying-Li Wu, Yan Hua; Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma. Blood Adv 2025; bloodadvances.2025015815. doi: https://doi.org/10.1182/bloodadvances.2025015815  March 6, 2025. 

Overview

This study reveals that the splicing factor RBM39 plays a crucial role in multiple myeloma (MM) growth and survival. Alternative splicing, a process that affects how genes are read and converted into proteins, is often disrupted in cancer. Researchers found that RBM39 is highly active in MM and is linked to poor patient outcomes. Knocking down RBM39 slowed MM cell growth, highlighting its potential as a therapeutic target.  

The study also tested indisulam, a drug that breaks down RBM39. In both lab tests and animal models, indisulam significantly suppressed MM growth. The loss of RBM39 led to widespread changes in gene splicing, particularly affecting MEK5, a protein important for MM cell survival. When MEK5 was altered due to RBM39 loss, MM cells lost their ability to grow and survive.  

Researchers discovered that targeting RBM39 or MEK5 enhanced the effectiveness of bortezomib, a common MM treatment, by blocking p65, a protein involved in cancer cell survival. These findings suggest that RBM39 could be a promising treatment target, paving the way for new, more effective strategies to combat MM.

 

 

"Ga-68 Pentixafor PET/CT in multiple myeloma and its correlation with clinical parameters: institutional pilot study"

Source

Gauthaman, D.K., Muthukrishnan, I., Acharya , K.A. et al. Ga-68 Pentixafor PET/CT in multiple myeloma and its correlation with clinical parameters: institutional pilot study. Ann Nucl Med (2025). https://doi.org/10.1007/s12149-025-02036-5  March 7, 2025. 

Overview

A new study highlights the potential of Ga-68 Pentixafor PET/CT as a powerful tool for staging and monitoring multiple myeloma (MM). This imaging method detects CXCR4 receptors, which are highly active in MM cells. Researchers evaluated 13 MM patients, using Ga-68 Pentixafor PET/CT to assess disease burden and compare it with standard clinical markers.

The results showed that Ga-68 Pentixafor PET/CT successfully identified MM in 12 out of 13 patients, with a sensitivity of 100%. The scan results also correlated with key clinical measures of MM severity, such as M-protein levels, beta-2 microglobulin, and bone marrow plasma cell infiltration. Importantly, the study found a significant link between PET/CT staging (Durie-Salmon Plus System) and the International Staging System (ISS), reinforcing its value in assessing disease progression.

This study suggests that Ga-68 Pentixafor PET/CT could be a reliable, non-invasive way to measure whole-body disease burden in MM. Researchers also propose combining this scan with F-18 FDG PET/CT to better understand tumor differences and improve prognostic insights. Additionally, Ga-68 Pentixafor PET/CT may play a key role in developing CXCR4-targeted treatments, offering new possibilities for personalized MM care.

 

 

"Treatment of Multiple Myeloma in Patients Refractory to Daratumumab/Anti-CD38 Monoclonal Antibodies: A Systematic Review"

Source

Tan, C.J., Kacerek, D., Kampirapawong, N., Godara, A. and Chaiyakunapruk, N. (2025), Treatment of Multiple Myeloma in Patients Refractory to Daratumumab/Anti-CD38 Monoclonal Antibodies: A Systematic Review. Cancer Med, 14: e70585. https://doi.org/10.1002/cam4.70585  March 7, 2025. 

Overview

For patients with multiple myeloma who no longer respond to Darzalex® (daratumumab), an anti-CD38 antibody, choosing the next treatment can be challenging. A recent review analyzed clinical trial data to compare treatment options for this group of patients.  

Researchers reviewed 23 clinical trials from 2015 to 2023, evaluating various therapies, including CAR T-cell therapy, BCMA-targeted antibodies, monoclonal antibodies, and other targeted drugs. The findings showed that CAR T-cell therapy had the highest response rates and longest survival times. Other BCMA-targeted treatments, such as elranatamab and teclistamab, also showed strong results, improving response rates and long-term outcomes.  

The study suggests that BCMA-directed therapies, particularly CAR T-cell therapy and bispecific antibodies, offer promising options for patients who are resistant to daratumumab. However, more research from randomized clinical trials is needed to establish clear treatment guidelines.

 

 

"Profilin 1 induces drug resistance by downregulating CD138 expression via autophagy in multiple myeloma"

Source

Wang, Y., Dai, Z., Xiao, S. et al. Profilin 1 induces drug resistance by downregulating CD138 expression via autophagy in multiple myeloma. Discov Onc 16, 284 (2025). https://doi.org/10.1007/s12672-025-02036-x  March 8, 2025. 

Overview

Velcade® (bortezomib) is a key drug for treating multiple myeloma (MM), but some patients develop resistance to it. This study explored how a protein called Profilin 1 (PFN1) contributes to bortezomib resistance and its connection to CD138, a marker found on MM cells.  

Researchers analyzed MM patient bone marrow samples and genetic data, finding a link between PFN1, CD138, and autophagy—a process that helps cells survive under stress. Lab experiments showed that when PFN1 levels increased, CD138 levels dropped due to autophagy. Since MM cells without CD138 are more resistant to treatment, this loss made the cells less responsive to bortezomib. However, blocking autophagy or restoring CD138 levels helped reverse drug resistance.  

These findings suggest that targeting PFN1, CD138, or the autophagy process could help overcome bortezomib resistance in MM, offering new potential treatment strategies.

 

 

"The Monoclonal Gammopathy of Undetermined Significance-Like (MGUS-like) Classifier Stratifies Prognosis in Multiple Myeloma: Results from Real-World Data in Chinese Population"

Source

Wenqiang Yan, Jieqiong Zhou, Yuntong Liu, Jingyu Xu, Jian Cui, Chenxing Du, Shuaishuai Zhang, Rui Lv, Weiwei Sui, Shuhui Deng, Yan Xu, Shuhua Yi, Dehui Zou, Mu Hao, Lugui Qiu, Gang An, The Monoclonal Gammopathy of Undetermined Significance-Like (MGUS-like) Classifier Stratifies Prognosis in Multiple Myeloma: Results from Real-World Data in Chinese Population, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.03.002. March 8, 2025.  

Overview

While genetic abnormalities are key in predicting prognosis in multiple myeloma (MM), new research suggests that the composition of plasma cells in the bone marrow also plays an important role.

Scientists have identified a subgroup of MM patients with a plasma cell profile similar to monoclonal gammopathy of undetermined significance (MGUS), a precursor condition to MM. This "MGUS-like" phenotype is linked to better long-term disease control and survival, even if patients don’t achieve complete remission.

To help classify patients, the PETHEMA/GEM Cooperative Group developed an open-access tool that categorizes MM cases into three risk groups: MGUS-like, intermediate, and MM-like, based on bone marrow plasma cell composition. Since treatment approaches differ worldwide, researchers now aim to validate this classification system in real-world Asian populations before recommending its broader use.

 

 

"Fuling decoction protects against bone destruction via suppressing exosomal ERK1 in multiple myeloma"

Source

Manya Yu, Jie Zhang, Jiaqi Fu, Suzhen Li, Xing Cui, Guizhi Fuling decoction protects against bone destruction via suppressing exosomal ERK1 in multiple myeloma., Phytomedicine, 2025,156627, ISSN 0944-7113, https://doi.org/10.1016/j.phymed.2025.156627. March 8, 2025. 

Overview

Bone damage is a common and serious complication of multiple myeloma (MM), reducing both quality of life and survival. Researchers are exploring new treatments that target how myeloma cells interact with bone tissue. One promising option is Guizhi Fuling Decoction (GZFL), a traditional herbal medicine. A recent study found that GZFL can help prevent bone loss by blocking the effects of harmful exosomes—tiny messengers released by myeloma cells that activate ERK1, a protein linked to bone destruction. By reducing ERK1 levels, GZFL helped slow bone damage in lab and animal studies.  

A clinical trial tested GZFL capsules in combination with standard MM treatment (bortezomib and dexamethasone). Patients who received this combination experienced less bone pain, lower ERK1 and RANKL levels (both associated with bone loss), and slower disease progression. These findings suggest that GZFL could be a useful addition to multiple myeloma treatment, offering better bone protection alongside existing therapies. Further research will help confirm its long-term benefits.

 

 

"Prodigiosin inhibits prolifiration and induces apoptosis through influencing amino acid metabolism in multiple myeloma"

Source

Bingjie Wang, Rui Shi, Wanqing Du, Jiaojiao Guo, Nihan He, Yinghong Zhu,  HanYu, Hongyu Lu, Liyuan Zhong, Xingli Li, Wen Zhou, Fei Yang, Xiangling Feng, Prodigiosin inhibits prolifiration and induces apoptosis through influencing amino acid metabolism in multiple myeloma, Bioorganic Chemistry, 2025, 108349, ISSN 0045-2068, https://doi.org/10.1016/j.bioorg.2025.108349. March 9, 2025

Overview

Multiple myeloma (MM) can be difficult to treat due to drug resistance and the high cost of treatments. A promising new approach to fighting MM involves prodigiosin, a natural compound with anti-cancer properties. Researchers found that prodigiosin can slow the growth of MM cells and even trigger cell death, without harming normal B cells. It also showed effectiveness in mice with MM. Prodigiosin works by interfering with how MM cells use amino acids, which are essential for cancer cell growth. This disrupts the cell’s ability to grow and multiply.

Through detailed testing, scientists discovered that prodigiosin affects the expression of key proteins involved in amino acid metabolism. By decreasing the use of amino acids, prodigiosin slows down MM cell growth. This research points to prodigiosin as a potential new, low-cost treatment option for MM. It could offer an alternative to expensive drugs, helping to reduce the burden on patients while providing an effective therapy.

 

 

"Myeloma cell intrinsic ANXA1 elevation and T cell dysfunction contribute to BCMA-negative relapse after CAR-T therapy"

Source

Shuangshuang Yang, Guixiang Wang, Jiahuan Chen, Wu Zhang, Jing Wu, Weiqing Liu, Ling Bai, Peide Huang, Jianqing Mi, Jie Xu, Myeloma cell intrinsic ANXA1 elevation and T cell dysfunction contribute to BCMA-negative relapse after CAR-T therapy, Molecular Therapy, 2025, ISSN 1525-0016, https://doi.org/10.1016/j.ymthe.2025.03.001. March 8, 2025. 

Overview

Relapse of multiple myeloma (MM) can happen even after patients experience long-term remission with anti-BCMA chimeric antigen receptor T (CAR-T) cell therapy. In this study, researchers examined a patient who relapsed 12 months after CAR-T treatment. They found that the CAR-T cells in the patient's bone marrow showed signs of exhaustion and decreased ability to grow. The myeloma cells that returned had low or no expression of BCMA, a key target for CAR-T therapy, but they still shared the same genetic markers as the original tumor. 

Further analysis revealed that these BCMA-negative myeloma cells had high levels of ANXA1, a protein linked to poor prognosis in MM. When the researchers tested these cells in the lab, they found that ANXA1 helped these BCMA-negative cells grow and weakened the CAR-T cells' ability to target them. In animal models, blocking ANXA1 reduced the growth of BCMA-negative myeloma cells. This suggests that targeting ANXA1 could be a promising strategy to improve CAR-T therapy and help eliminate these resistant cancer cells.

 

 

"The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells"

Source

Hong Phuong Nguyen, Enze Liu, Anh Quynh Le, Mahesh Lamsal, Jagannath Misra, Sankalp Srivastava, Harikrishnan Hemavathy, Reuben Kapur, Mohammad Abu Zaid, Rafat Abonour, Ji Zhang, Ronald C. Wek, Brian A. Walker, Ngoc Tung Tran, The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells, Molecular Therapy Oncology, 2025, 200964, ISSN 2950-3299, https://doi.org/10.1016/j.omton.2025.200964. March 8, 2025. 

Overview

Multiple myeloma (MM) can be difficult to treat and often leads to severe symptoms. Finding new treatment targets is essential for improving outcomes. In this study, researchers identified a protein complex called oligosaccharyltransferase (OST) as a new target for MM cells. High levels of the OST complex are linked to relapsed, high-risk MM and poor patient outcomes. When the OST complex was disrupted, it slowed MM cell growth, caused the cells to stop dividing, and triggered cell death. 

In laboratory tests, combining OST inhibition with Velcade® (bortezomib), a common treatment for MM, worked better to kill MM cells compared to using bortezomib alone. The combination therapy also helped fight off bortezomib-resistant cancer cell traits. The OST complex disruption worked by affecting several key pathways involved in MM growth, such as mTORC1, glycolysis, and MYC, and also promoted a specific type of cell death (apoptosis). This research suggests that targeting the OST complex, especially in combination with bortezomib, could offer a new, effective approach for treating relapsed MM.

 

 

"Retrospective analysis of treatment discontinuation in minimal residual disease negative multiple myeloma"

Source

Sato, S., Sawazaki, E., Tsunoda, S. et al. Retrospective analysis of treatment discontinuation in minimal residual disease negative multiple myeloma. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-03966-6  March 9, 2025. 

Overview

In multiple myeloma (MM), minimal residual disease (MRD) negativity is an important indicator of treatment success. However, in real-world clinical practice, stopping treatment after achieving MRD negativity may reduce healthcare costs and minimize side effects. This study looked at MM patients who reached MRD negativity and then stopped treatment to see what happened.

The study included 39 MM patients, with 17 eligible for autologous stem cell transplantation and 22 ineligible. On average, patients went 42.4 months before needing more treatment. After 12 months, only 11.7% of patients relapsed, and by 48 months, 26.4% had relapsed. The study found that higher levels of lactate dehydrogenase (LDH) and a specific genetic abnormality (t(4;14)) were linked to worse outcomes. Interestingly, 20% of patients with a lower risk of disease (based on staging and no other risk factors) had no recurrence even after stopping treatment.

The findings suggest that for low-risk MM patients, stopping treatment after achieving MRD negativity could be safe and may lead to long-term remission, but stopping treatment in high-risk cases may not be as safe.

 

 

"A real-world experience of efficacy and safety of belantamab mafodotin in relapsed refractory multiple myeloma"

Source

Dileo, R., Mewawalla, P., Babu, K. et al. A real-world experience of efficacy and safety of belantamab mafodotin in relapsed refractory multiple myeloma. Blood Cancer J. 15, 34 (2025). https://doi.org/10.1038/s41408-025-01226-8  March 10, 2025. 

Overview

This study looked at the real-world use of Blenrep (belantamab mafodotin), a treatment for relapsed/refractory multiple myeloma (RRMM), in 81 patients who had already undergone multiple lines of therapy. Most of these patients had high-risk disease, with over half having extramedullary disease (EMD), a feature linked to worse outcomes. Despite this, the treatment showed promising results: 40% of patients had a good response, with 15% achieving complete remission. However, patients with EMD or advanced disease had lower response rates.

The treatment was generally well-tolerated, though nearly 70% of patients experienced eye problems (ocular toxicity), and about half of the patients stopped treatment due to these side effects. Blood-related issues, like low platelet and red blood cell counts, were also common. The study found that patients with EMD had worse outcomes, but overall, belantamab mafodotin showed similar efficacy and safety to earlier trials, even for those who were considered ineligible for clinical trials due to severe disease or side effects.

The results suggest that belantamab mafodotin is a viable option for patients with heavily pretreated RRMM, though its eye-related side effects remain a significant concern. Further research on optimizing dosing and combining treatments to reduce these side effects is needed.

 

 

"Significant attenuation of fully automated thrombin generation in newly diagnosed multiple myeloma patients after induction therapy"

Source

Velasco-Rodríguez, D., Martínez-Alfonzo, I., Velasco-Valdazo, A.E. et al. Significant attenuation of fully automated thrombin generation in newly diagnosed multiple myeloma patients after induction therapy. J Thromb Thrombolysis (2025). https://doi.org/10.1007/s11239-025-03079-1  March 10, 2025. 

Overview

This study looked at changes in blood clotting (thrombosis) in patients with newly diagnosed multiple myeloma (NDMM) after receiving treatment. Around 10% of these patients develop a blood clot during their disease course, despite taking preventive measures. The study used a fully automated test to measure thrombin generation (TG), which helps assess blood clotting risk.

The study included 100 NDMM patients and measured TG at the start of treatment, after 1 cycle, and after 4 cycles. The results showed that after treatment, there was a significant decrease in blood clotting activity, especially after 4 cycles. Patients on proteasome inhibitors (PI) had the most notable reduction in clotting measures, while those on daratumumab-containing treatments had a temporary increase after the first cycle.

Interestingly, the study found no connection between the depth of the response to treatment and changes in clotting activity. Additionally, while blood clotting can increase the risk of death, there was no link between baseline clotting levels and the development of blood clots (VTE). Overall, treatment for myeloma seems to reduce hypercoagulability, particularly with PI-based therapies.

 

 

"Effect of metachronous primary and secondary solid cancers in patients with multiple myeloma: a retrospective study from a single-center"

Source

Ji Y, Li H, Zhang H, Cheng H, Wang Y, Xu K, Li Z. Effect of metachronous primary and secondary solid cancers in patients with multiple myeloma: a retrospective study from a single-center. Front Immunol. 2025 Mar 10;16:1516471. doi: 10.3389/fimmu.2025.1516471. March 10, 2025. 

Overview

This study explored how having another solid cancer (metachronous primary malignant solid tumor or MPMST) affects the survival and prognosis of patients with multiple myeloma (MM). The research found that older patients (ages 65 and up) with MM have a higher risk of developing MPMST. The study also showed that male patients, those over 65, and patients with advanced MM (ISS stage III) had a worse prognosis when they also had MPMST. 

The most common cancers found before or after MM were lung, thyroid, and breast cancer. Patients with MM who had CAR-T cell therapy did not have a higher risk of developing these second cancers or live longer than others. 

Overall, the study highlighted that patients with MM and MPMST, especially older men and those with advanced disease, face greater challenges and worse outcomes, providing useful information for treating these patients more effectively.

 

 

"Impact of myosteatosis on prognosis in multiple myeloma patients: A subgroup analysis of 182 cases and development of a nomogram"

Source

Jun-Peng Liu, Xing-Chen Yao, Ming Shi, Zi-Yu Xua, Yue Wu, Xiang-Jun Shi, Meng Li, Xin-Ru Du, Impact of myosteatosis on prognosis in multiple myeloma patients: A subgroup analysis of 182 cases and development of a nomogram, Journal of Bone Oncology, 2025, 100670, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2025.100670. March 11, 2025. 

Overview

This study looked at the role of myosteatosis (fatty infiltration in muscles) in predicting outcomes for multiple myeloma (MM) patients. The research analyzed data from 182 MM patients who had MRI scans to measure the fatty infiltration rate (FIR) in specific muscles. The study found that myosteatosis didn't affect survival rates in MM patients, but it was linked to an increased risk of fractures. Factors like age, sex, body mass index (BMI), and red blood cell count influenced the degree of myosteatosis.

While myosteatosis did not predict survival, it was a helpful indicator for fractures, especially in patients with higher BMI or red blood cell counts. A model using FIR was created to predict fracture risk and was found to be effective in clinical practice. The study concluded that myosteatosis is important for predicting fractures and is related to back pain and functional impairment but is not a reliable indicator for survival in MM patients.

 

 

"Discovery of a novel class NSD2 inhibitor for t(4;14)-positive multiple myeloma"

Source

Sae Matsuoka, Naoki Osada, Hirokazu Kubota, Ko Kikuzato, Hiroo Koyama, Takeshi Sonoda, Akiko Idei, Minoru Yoshida, Masaki Kikuchi, Takashi Umehara, Chiduru Watanabe, Teruki Honma, Hiroshi Yasui, Sho Ikeda, Naoto Takahashi, Hideki Nakasone, Jiro Kikuchi, Yusuke Furukawa, Discovery of a novel class NSD2 inhibitor for t(4;14)-positive multiple myeloma, Blood Neoplasia, 2025, 100091, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100091. March 11, 2025. 

Overview

This study focuses on a specific genetic abnormality, t(4;14), which is found in about 15% of multiple myeloma (MM) patients and makes the cancer harder to treat. The abnormality causes the MM cells to produce a protein called NSD2, which makes them resistant to standard treatments. The researchers identified a new drug, RK-0080552 (RK-552), which targets NSD2. In tests, RK-552 was found to be effective at killing MM cells with the t(4;14) abnormality, both in lab studies and in mice. The drug worked by reducing a key gene’s activity and affecting the cells’ DNA. RK-552 also worked well alongside another drug, pomalidomide, and increased survival in mice without causing harmful side effects. This study suggests that RK-552 could become an important part of treatment for MM patients with t(4;14), offering a promising new option for improving their outcomes.

 

 

"Tissue factor-bearing extracellular vesicles, procoagulant phospholipids and D-dimer as potential biomarkers for venous thromboembolism in patients with newly diagnosed multiple myeloma: A comprehensive analysis"

Source

S. Charles, T. Fatrara, T. Bouriche, A. Bonifay, T. Lecompte, F. Dignat-George, B. Tardy, C. Frere, R. Lacroix, E. Chalayer, Tissue factor-bearing extracellular vesicles, procoagulant phospholipids and D-dimer as potential biomarkers for venous thromboembolism in patients with newly diagnosed multiple myeloma: A comprehensive analysis,Thrombosis Research, Volume 247, 2025, 109256, ISSN 0049-3848, https://doi.org/10.1016/j.thromres.2025.109256. March 2025. 

Overview

This study looks at biomarkers that could help predict the risk of blood clots (venous thromboembolism or VTE) in patients with newly diagnosed multiple myeloma (MM) who are starting anti-myeloma treatment. The researchers focused on three biomarkers: tissue factor-bearing microvesicles (MV-TF), procoagulant phospholipids (procoag-PPL), and D-dimer. They found that MV-TF levels were higher in patients who developed VTE, both before and during treatment. D-dimer levels were also higher during treatment in patients who had VTE. However, there were no significant differences in procoag-PPL clotting times between the groups. The study suggests that measuring MV-TF and D-dimer levels could help improve the prediction of VTE risk in MM patients, but more research is needed to confirm these findings, especially with newer MM treatments.

 

 

 

"A comparison of Cryopreserved and non-Cryopreserved Peripheral Blood Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma: A study from the Chronic Malignancies Working Party of the EBMT"

Source

Mohammed Amine Bekadja, Luuk Gras, Laurien Baaij, Linda Koster, Nada Hamad, Ben Carpenter, Emma Nicholson, Victoria Potter, Annoek E.C. Broers, Didier Blaise, Jenny Louise Byrne, Anne Huynh, Francesca Kinsella, Péter Reményi, Matthew P. Collin, John G. Gribben, Simon Bulley, Alessandra Tucci, Natalia De Las Heras, Joanna Drozd-Sokolowska, Kavita Raj, Meral Beksac, Stefan Schönland, Patrick J Hayden, John Snowden, Mahmoud Deeb Aljurf, Donal P McLornan, Damiano Rondelli, A. Sureda, Laurent Garderet, Dietger Niederwieser, A comparison of Cryopreserved and non-Cryopreserved Peripheral Blood Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma: A study from the Chronic Malignancies Working Party of the EBMT, Cytotherapy, 2025, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2025.02.008.  March 7, 2025. 

Overview

This study compared the outcomes of autologous hematopoietic cell transplants (AHCT) using non-cryopreserved (NCP) peripheral blood stem cells (PBSC) versus cryopreserved (CP) PBSC in multiple myeloma (MM) patients. The researchers matched 407 patients from Algeria who received NCP PBSC with 1,412 patients from European centers who received CP PBSC. Both groups had similar times to neutrophil and platelet engraftment, with no significant differences in non-relapse mortality. However, the relapse rate was lower and progression-free survival (PFS) was longer in the NCP group. Overall survival rates were similar for both groups. The study concluded that using fresh stem cells is an acceptable alternative to frozen stem cells for MM patients, especially in areas with limited resources.

 

 

"Enhancing T cell cytotoxicity in multiple myeloma with bispecific αPD-L1 × αCD3 T cell engager-armed T cells and low-dose bortezomib therapy"

Source

Nunghathai Sawasdee, Chutamas Thepmalee, Mutita Junking, Seiji Okada, Aussara Panya, Pa-thai Yenchitsomanus, Enhancing T cell cytotoxicity in multiple myeloma with bispecific αPD-L1 × αCD3 T cell engager-armed T cells and low-dose bortezomib therapy, Biomedicine & Pharmacotherapy, Volume 184,2025, 117878, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2025.117878.  March 2025. 

Overview

This study looked at how low-dose Velcade® (bortezomib) affects a protein called PD-L1 in multiple myeloma (MM) cells and how it could improve the effectiveness of T cell-based therapies. The researchers used a special type of T cell that targets both PD-L1 on cancer cells and CD3 on T cells (called BATs). They found that BATs helped activate T cells to fight cancer, but they didn't kill the cancer cells directly. When combined with bortezomib, BATs were more effective at killing MM cells, especially in certain cell lines. This suggests that combining BATs with bortezomib could be a promising treatment for MM, even in cases resistant to bortezomib.

 

 

"Disparities and diagnostic delays: multiple myeloma, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology"

Source

Dr. Almas Binnal, Dr. Ghaidaa Badabaan, Dr. Anita Gohel, Disparities and diagnostic delays: multiple myeloma, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 139, Issue 3, 2025, Page e77, ISSN 2212-4403, https://doi.org/10.1016/j.oooo.2024.11.026. March 2025. 

Overview

This case report highlights two older female patients who experienced a delay in diagnosing multiple myeloma, a rare blood cancer. One patient had pain in her jaw, which was initially misdiagnosed and worsened with physical therapy. The other experienced numbness in her jaw but could not pinpoint the cause. Both had distinct areas of bone damage seen in scans, leading to the diagnosis of multiple myeloma with plasmacytoma, a related condition. Histopathology confirmed the diagnosis, and further tests revealed specific abnormal plasma cells. The report emphasizes the importance of early diagnosis and treatment, as multiple myeloma can be hard to identify and often leads to delayed diagnoses. Early treatment helps reduce complications and improves survival and quality of life.

 

 

"Abstract No. 54 Efficacy of Radiofrequency Ablation and Kyphoplasty for the Palliation of Pain Related to Multiple Myeloma, Journal of Vascular and Interventional Radiology"

Source

R. Pigg, B. Mainali, J. Newsome, J. Gichoya, P. Park, Abstract No. 54 Efficacy of Radiofrequency Ablation and Kyphoplasty for the Palliation of Pain Related to Multiple Myeloma, Journal of Vascular and Interventional Radiology, Volume 36, Issue 3, Supplement, 2025, Page S25, ISSN 1051-0443, https://doi.org/10.1016/j.jvir.2024.12.086. March 2025. 

Overview

This study evaluated the effectiveness of radiofrequency (RF) ablation and kyphoplasty in relieving pain from bone lesions caused by multiple myeloma. The study involved 102 patients with 163 spinal or pelvic lesions. All procedures were successful, and patients experienced significant pain relief and reduced opioid use after the treatments. Pain scores improved from an average of 7.4 out of 10 before the procedure to 2.4 just a few days after, with long-term relief lasting up to 400 days. Opioid usage also decreased significantly. No major procedure-related side effects were observed. Overall, the study found that RF ablation followed by kyphoplasty is an effective way to manage pain from multiple myeloma-related bone lesions.

 

 

"Belantamab mafodotin monotherapy for relapsed or refractory multiple myeloma: a real-world observational study in the United States"

Source

Hultcrantz M, Kleinman D, Vij R, Escalante F, Delforge M, Kotowsky N, Bitetti J, Boytsov N, Camadoo-O’Byrne L, Happ LP, Germain G, Urosevic A, Mahendran M, Duh MS, Laliberte F, Cavo M, Lee HC. Belantamab mafodotin monotherapy for relapsed or refractory multiple myeloma: a real-world observational study in the United States. Haematologica 2025;110(3):753-757; https://doi.org/10.3324/haematol.2024.285893.  March 2025. 

Overview

Blenrep (belantamab mafodotin) is a treatment for relapsed or refractory multiple myeloma (MM) that targets cancer cells by binding to B-cell maturation antigen (BCMA). It was approved in the U.S. in 2020 but had its approval withdrawn in 2023 after a study showed it wasn't better than other treatments for progression-free survival. New studies are testing its use in combination with other therapies. This real-world study focused on how ocular (eye-related) side effects are managed in patients using belantamab mafodotin. It found that nearly 50% of patients experienced eye problems, with the most common being keratopathy (damage to the cornea), blurred vision, and dry eyes. The severity of eye issues varied, but most cases were mild. 

 

 

"Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with highrisk cytogenetics: the IFM 2014-01 study"

Source

Bobin A, Manier S, de Keizer J, Srimani JK, Hulin C, Karlin L, Caillot D, Lafon I, Mariette C, Araujo C, Arnulf B, Bareau B, Belhadj K, Benboubker L, Braun T, Calmettes C, Decaux O, Dib M, Demarquette H, Jacquet C, Sonntag C, Godet S, Jaccard A, Lenain P, Macro M, Richez-Olivier V, Tiab M, Vincent L, Zerazhi H, Pétillon M-O, Rollet S, Gardeney H, Durand G, Levy A, Touzeau C, Perrot A, Moreau P, Facon T, Corre J, Ragot S, Avet-Loiseau H, Leleu X. Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with highrisk cytogenetics: the IFM 2014-01 study. Haematologica 2025;110(3):758-763; https://doi.org/10.3324/haematol.2024.285916.  March 2025.  

Overview

A recent study tested a new treatment for high-risk multiple myeloma (MM) patients who have certain genetic changes (del[17p] or t[4;14]). These patients often have shorter survival times and quickly develop resistance to treatments. The study combined ixazomib (a proteasome inhibitor) with pomalidomide and dexamethasone (IxPd) to see if it could improve survival while being easier to take than other treatments. The study included 26 patients who had previously been treated with lenalidomide but were still eligible for other treatments. The main goal was to see how long it took for the disease to progress (time to progression or TTP).

After a median follow-up of 27 months, the results showed that the median TTP improved to 10.2 months, which is more than three times longer than what was seen in previous studies with pomalidomide and dexamethasone alone. The treatment was generally safe, though most patients experienced side effects, and some needed to stop treatment due to disease progression. The study confirmed that adding ixazomib to the treatment regimen could be beneficial, especially for patients with the t(4;14) genetic change. However, the benefit was limited for some patients, and more research is needed to fully confirm the treatment's effectiveness.

 

 

"Comparison of EasyM, a clonotypic mass spectrometry assay, and EuroFlow minimal residual disease assessment in multiple myeloma"

Source

Zhao J, Khong T, Gorniak M, Khaled A, McDonald Z, Reynolds J, Mithraprabhu S, Bingham N, Lim S, Wong D, Johnston A, Motorna O, Murphy N, Quach H, Yang L, Spencer A. Comparison of EasyM, a clonotypic mass spectrometry assay, and EuroFlow minimal residual disease assessment in multiple myeloma. Haematologica 2025;110(3):764-767; https://doi.org/10.3324/haematol.2024.285933.  March 2025.  

Overview

A new approach for measuring minimal residual disease (MRD) in multiple myeloma (MM) is using a blood test called EasyM, which analyzes M-proteins in peripheral blood using mass spectrometry (MS). This test may be more sensitive and less invasive than traditional bone marrow (BM) testing methods like next-generation flow cytometry (NGF), which requires a bone marrow biopsy.

In a study, researchers compared EasyM with BM-based NGF testing in MM patients who were receiving different treatments in clinical trials. The results showed that EasyM was able to detect M-protein levels in the blood even when NGF testing was negative, suggesting it could be a better tool for monitoring residual disease. In fact, EasyM detected rising M-protein levels that predicted relapse months earlier than traditional methods.

Of the 62 patients analyzed, the majority had successful MS testing, with a small group of patients (5%) showing no detectable M-protein. The study found that EasyM could detect disease even in patients who were clinically in remission, highlighting its potential for early relapse detection and for complementing bone marrow-based MRD testing.

This study suggests that EasyM could be a valuable, more sensitive alternative to bone marrow testing for MRD monitoring in MM, potentially leading to more accurate and timely treatment adjustments. However, further research and validation are needed to confirm these findings and determine the best use of this method in clinical practice.

 

 

"Impact of daratumumab/bortezomib/thalidomide and dexamethasone induction therapy on chemo-free stem cell mobilization in transplant-eligible newly diagnosed multiple myeloma: a multicenter real-world experience"

Source

Porrazzo M, Moscato T, Sapienza G, Accardi F, Patti C, Cangialosi C, Costanza C, Bono R, Tringali S, Rotolo C, Gigliotta E, Rizzuto A, Ingrascè MG, Butera G, Di Noto L, Santoro A, Marfia A, Botta C, Siragusa S, Martino M, Castagna L. Impact of daratumumab/bortezomib/thalidomide and dexamethasone induction therapy on chemo-free stem cell mobilization in transplant-eligible newly diagnosed multiple myeloma: a multicenter real-world experience. Haematologica 2025;110(3):791-794; https://doi.org/10.3324/haematol.2024.286332.  March 2025. 

Overview

In the treatment of transplant-eligible newly diagnosed multiple myeloma (TE-NDMM), patients typically receive quadruplet induction therapy, which includes the anti-CD38 monoclonal antibody daratumumab. This is followed by high-dose melphalan and autologous stem cell transplantation (ASCT). A key step in the transplant process is the mobilization of peripheral blood stem cells, which can be done using chemotherapy, such as cyclophosphamide, combined with granulocyte colony-stimulating factor (G-CSF), or a chemo-free method using G-CSF alone, sometimes with plerixafor.

Recent studies have raised concerns about how anti-CD38 monoclonal antibodies like daratumumab might affect stem cell mobilization. These concerns are based on the idea that daratumumab may cause certain cells to overproduce molecules that interfere with stem cell mobilization. In clinical trials, patients receiving daratumumab-based therapies often required more use of plerixafor and experienced lower stem cell yields compared to those receiving other treatments.

In a large observational study, 100 TE-NDMM patients who received quadruplet therapy including daratumumab and were mobilized with G-CSF and plerixafor were analyzed. The study aimed to evaluate the success of stem cell mobilization, the need for plerixafor, and the number of CD34+ cells harvested. The results showed that 90% of patients successfully mobilized enough stem cells using the chemo-free method, with many achieving optimal yields without needing plerixafor. However, a small group (10%) required a second, chemotherapy-based strategy due to failed mobilization.

The study also found that factors like a longer gap between the last daratumumab dose and stem cell collection, as well as better overall health scores, were linked to higher stem cell yields. While chemo-free mobilization was effective for most patients, chemo-based mobilization remains the preferred choice for those undergoing tandem high-dose chemotherapy.

Chemo-free mobilization is a feasible and effective option for patients treated with daratumumab-based therapy, though chemo-based strategies may still be necessary in some cases, especially for those needing multiple rounds of high-dose chemotherapy.

 

 

"Efficacy of Radiofrequency Ablation in Pain Relief and Tumor Reduction in Multiple Myeloma Patients with Osteolytic Lesions, Journal of Vascular and Interventional Radiology"

Source

P. Torkian, A. Peterson, S. Wallace, S. Flanagan, P. Shrestha, R. Talaie, Abstract No. 55 Efficacy of Radiofrequency Ablation in Pain Relief and Tumor Reduction in Multiple Myeloma Patients with Osteolytic Lesions, Journal of Vascular and Interventional Radiology, Volume 36, Issue 3, Supplement, 2025, Pages S25-S26, ISSN 1051-0443, https://doi.org/10.1016/j.jvir.2024.12.087. March 2025. 

Overview

Managing pain in multiple myeloma (MM) patients with bone lesions is often challenging. This study looked at how well radiofrequency ablation (RFA), a treatment typically used for other conditions, worked for pain relief and reducing tumor size in MM patients.

The study reviewed 20 patients with painful vertebral lesions who had RFA. Pain was measured using the Visual Analog Scale (VAS), and the patients' functional abilities were assessed using the Oswestry Disability Index (ODI) and Karnofsky Performance Status (KPS). Tumor size was checked using MRI and PET-CT.

Results showed that RFA significantly reduced pain, with VAS scores dropping from 8.2 (severe pain) to 4.1 at one month and staying around 4.7 after 12 months. Functional abilities also improved, with ODI scores decreasing by 46% and KPS scores improving by 32% within six months. Imaging revealed a 51% decrease in tumor size and a 63% reduction in the tumor's activity level.

In conclusion, RFA is an effective treatment for reducing pain and tumor size in MM patients with bone lesions, offering significant improvements in both pain relief and overall function. This suggests that RFA could be a helpful option for managing these types of bone problems in MM patients.

 

 

"NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma"

Source

Debora Soncini, Pamela Becherini, Francesco Ladisa, Silvia Ravera, Adithya Chedere, Elisa Gelli, Giulia Giorgetti, Claudia Martinuzzi, Francesco Piacente, Luca Mastracci, Claudia Veneziano, Gianluca Santamaria, Fiammetta Monacelli, Moustafa S. Ghanem, Antonia Cagnetta, Fabio Guolo, Matteo Garibotto, Sara Aquino, Mario Passalaqua, Santina Bruzzone, Axel Bellotti, Michel A. Duchosal, Aimable Nahimana, Emanuele Angelucci, Chandra Nagasuma, Alessio Nencioni, Roberto Massimo Lemoli, Michele Cea; NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma. Blood Adv 2025; 9 (5): 1024–1039. doi: https://doi.org/10.1182/bloodadvances.2024013425  March 11, 2025. 

Overview

In multiple myeloma (MM), high levels of an enzyme called NAMPT, which helps produce a molecule called NAD+, are common. However, treatments that block NAMPT have not worked well in clinical trials because MM cells can still produce NAD+ using other pathways. This study looked more closely at how MM cells make NAD+ and discovered that another enzyme, NAPRT, helps MM cells produce NAD+ using a different route. 

By removing NAPRT from MM cells, researchers found that the cells became more vulnerable to stress and damage. When they also inhibited NAMPT, the MM cells became more sensitive to the chemotherapy drug melphalan. These findings suggest that targeting both NAMPT and NAPRT could be a new way to treat MM, particularly for patients with more aggressive forms of the disease. This combined approach is worth testing in future clinical trials.

 

 

"Cumulative deficits frailty index and relationship status predict survival in multiple myeloma"

Source

Nadine Abdallah, Paul Dizona, Amanika Kumar, Betsy LaPlant, Terri Menser, Gavin Schaeferle, Sarah Aug, Megan Weivoda, Angela Dispenzieri, Francis K. Buadi, Rahma Warsame, Joselle Cook, Martha Q. Lacy, Suzanne Hayman, Morie A. Gertz, S. Vincent Rajkumar, Shaji K. Kumar; Cumulative deficits frailty index and relationship status predict survival in multiple myeloma. Blood Adv 2025; 9 (5): 1137–1146. doi: https://doi.org/10.1182/bloodadvances.2024014624  March 11, 2025. 

Overview

This study looked at the impact of frailty, relationship status, and socioeconomic factors on patients with newly diagnosed multiple myeloma (MM). Researchers examined 515 MM patients who were diagnosed between 2005 and 2018. They used a frailty index (FI) to measure frailty, based on patients' daily activities and health problems. Patients with a FI of 0.15 or higher were considered frail. The study found that frail patients had worse health outcomes, including a higher disease stage, less chance of receiving early transplant, and lower survival rates. Frailty was also linked to worse reported symptoms like fatigue, pain, and quality of life. Social support, such as being married or in a relationship, was linked to better outcomes, but socioeconomic status (SES) didn't directly affect survival. The study concluded that frailty is an important factor in predicting patient outcomes and should be monitored during treatment.

 

 

"BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement"

Source

Mahmoud R. Gaballa, Omar Castaneda Puglianini, Adam Cohen, Dan Vogl, Alfred Chung, Christopher J. Ferreri, Peter Voorhees, Doris K. Hansen, Krina K. Patel; BCMA-directed CAR T-cell therapy in patients with multiple myeloma and CNS involvement. Blood Adv 2025; 9 (5): 1171–1180. doi: https://doi.org/10.1182/bloodadvances.2024014345  March 11, 2025. 

Overview

This study looked at the impact of frailty, relationship status, and socioeconomic factors on patients with newly diagnosed multiple myeloma (MM). Researchers examined 515 MM patients who were diagnosed between 2005 and 2018. They used a frailty index (FI) to measure frailty, based on patients' daily activities and health problems. Patients with a FI of 0.15 or higher were considered frail. The study found that frail patients had worse health outcomes, including a higher disease stage, less chance of receiving early transplant, and lower survival rates. Frailty was also linked to worse reported symptoms like fatigue, pain, and quality of life. Social support, such as being married or in a relationship, was linked to better outcomes, but socioeconomic status (SES) didn't directly affect survival. The study concluded that frailty is an important factor in predicting patient outcomes and should be monitored during treatment.

 

 

"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, Tim Campbell, Shari M. 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; 9 (5): 1132–1136. doi: https://doi.org/10.1182/bloodadvances.2024015285  March 11, 2025. 

Overview

This letter discusses the potential of combining anti–PD-1 therapy (nivolumab) with anti-BCMA chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) who relapse after CAR-T treatment. The study looked at four patients who received nivolumab after their CAR-T therapy stopped working. Results showed that while nivolumab worked for some, it didn’t help everyone. Two patients had a clinical response to nivolumab, and their T-cell profiles were different from those who did not benefit. The study suggests that the effectiveness of PD-1 inhibitors in combination with CAR-T therapy depends on the state of the patient’s T-cells at the time of relapse. It also proposes that monitoring the T-cell environment before treatment could help identify which patients would benefit from this combination therapy. More research is needed to explore the timing and best use of checkpoint inhibitors like nivolumab to improve outcomes for MM patients.

 

 

"Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma"

Source

Andrew J. Yee, Jacob P. Laubach, Erica L. Campagnaro, Brea C. Lipe, Omar Nadeem, Robb S. Friedman, Craig E. Cole, Elizabeth K. O’Donnell, Giada Bianchi, Andrew R. Branagan, Robert L. Schlossman, Samantha J. Shapiro, Cynthia C. Harrington, Jill N. Burke, Marilyn T. Gammon, Kathleen J. Lively, Cassandra A. Reimonn, Danielle X. Andrade, Robert Redd, Jens G. Lohr, Kenneth C. Anderson, Paul G. Richardson, Noopur S. Raje; Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma. Blood Adv 2025; 9 (5): 1163–1170. doi: https://doi.org/10.1182/bloodadvances.2024014717  March 11, 2025. 

Overview

The OPTIMISMM study showed that adding Empliciti® (elotuzumab), a monoclonal antibody, to the treatment combination of Pomalyst® (pomalidomide), Velcade® (bortezomib), and dexamethasone (PVd) could improve outcomes for patients with relapsed or refractory multiple myeloma (MM). A phase 2 trial tested this combination (elo-PVd) in 48 patients who had previously received at least one treatment line, including lenalidomide and a proteasome inhibitor. The results showed a 56.3% overall response rate (ORR) and a median progression-free survival (PFS) of 10 months. Patients who had only one prior treatment line had even better results, with a 73.7% ORR and a median PFS of 23.4 months. Common side effects included neutropenia, infections, and lung infections. This study is one of the first to test a quadruple combination therapy in relapsed/refractory MM and shows positive results, even in patients who had previously been treated with multiple therapies.

 

 

"Downregulated expression of dual-specificity phosphatase-1 in multiple myeloma as a predictor of poor survival outcomes"

Source

Guo, D., Lu, J., Hong, L., Liu, H., & Huang, H. (2025). Downregulated expression of dual-specificity phosphatase-1 in multiple myeloma as a predictor of poor survival outcomes. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2474271  March 12, 2025.  

Overview

This study investigates the role of Dual-specificity phosphatase-1 (DUSP1) in multiple myeloma (MM), a type of blood cancer. Researchers found that low levels of DUSP1 were linked to worse outcomes for MM patients. Specifically, lower DUSP1 levels were associated with higher levels of certain blood markers and worse survival rates. Patients with higher DUSP1 expression had better clinical outcomes. The study also found that DUSP1 interacts with various proteins and pathways that could help explain its role in MM. Overall, low DUSP1 expression may serve as a sign of poorer prognosis in MM patients.

 

 

"Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q+"

Source

Romanos Sklavenitis-Pistofidis, Elizabeth D Lightbody, Mairead Reidy, Junko Tsuji, Jean-Baptiste Alberge, Michelle P Aranha, Daniel Lewis Heilpern-Mallory, Harvey G. Roweth, Daisy Huyng, Stephen Jun Fei Chong, Anna Y. Chung, Jeremy Zhang, Liam Hackett, Nicholas J Haradhvala, Ting Wu, Nang Kham Su, Brianna Berrios, Saveliy Belkin, Ankit K. Dutta, Ryan A Knudson, Carolyn Brandt, Patricia T. Greipp, Matthew S. Davids, Maria Papaioannou, Gad Getz, Irene M Ghobrial, Salomon Manier; Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q+. Blood 2025; blood.2024025102. doi: https://doi.org/10.1182/blood.2024025102  March 12, 2025  

Overview

This study focuses on improving treatments for multiple myeloma (MM) patients with a genetic abnormality known as chromosome 1q gain (1q+), which is linked to a higher risk of disease progression and death. Researchers found that MM with 1q+ is more sensitive to certain drugs, including MCL1 and PI3K inhibitors. Using advanced techniques, they observed that 1q+ leads to higher activity in the MCL1 and PI3K pathways, making these drugs more effective. Combining these inhibitors showed even better results, offering a potential approach for treating MM with 1q+. This research could help develop more targeted therapies for a significant group of MM patients.

 

 

"Daratumumab-based quadruplet versus triplet induction regimens in transplant-eligible newly diagnosed multiple myeloma: a systematic review and meta-analysis"

Source

Souto Filho, J.T.D., Cantadori, L.O., Crusoe, E.d.Q. et al. Daratumumab-based quadruplet versus triplet induction regimens in transplant-eligible newly diagnosed multiple myeloma: a systematic review and meta-analysis. Blood Cancer J. 15, 37 (2025). https://doi.org/10.1038/s41408-025-01253-5  March 13, 2025. 

Overview

This study looked at the impact of adding Darzalex® (daratumumab), an antibody treatment, to traditional triple-drug regimens for transplant-eligible patients with newly diagnosed multiple myeloma (TE-NDMM). Researchers combined data from four clinical studies to compare the survival outcomes of quadruplet regimens (which include daratumumab) to triplet regimens. The analysis showed that the addition of daratumumab significantly improved both overall survival (OS) and progression-free survival (PFS). Specifically, patients who received daratumumab-based treatments had a lower risk of dying and a longer period without disease progression compared to those who received standard triple therapies. This evidence suggests that daratumumab-based quadruplet regimens may offer better long-term outcomes for TE-NDMM patients.

 

 

"Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems"

Source

Pooraskari, Z., Barri Ghazani, H., Piri, R. et al. Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems. Med Oncol 42, 107 (2025). https://doi.org/10.1007/s12032-025-02659-8  March 13, 2025 

Overview

This study tested AMG232, a drug that blocks MDM2, to see if it could help treat multiple myeloma (MM) by stopping the growth of blood vessels, a process called angiogenesis. The researchers grew MM cells (AMO-1) alongside endothelial cells (HUVECs), which are involved in blood vessel formation. They found that AMG232 killed MM cells in a dose-dependent manner, with a lower dose needed for MM cells than for HUVECs. When the cells were cultured together, they became more resistant to the drug, showing a protective effect between the two cell types. AMG232 also reduced the production of several proteins that help blood vessels grow, such as VEGF-A and IL-6, and it significantly slowed down HUVEC migration and tube formation, key steps in angiogenesis. Overall, AMG232 showed promise as a treatment for MM by both killing cancer cells and blocking the formation of new blood vessels that tumors need to grow.

 

 

"Significant Reduction in Peak Left Ventricular Global Longitudinal Strain in Multiple Myeloma Patients: A Pilot Random Awareness Analysis"

Source

Sawalha K, Fancher A J, Vallurupalli S, et al. (March 13, 2025) Significant Reduction in Peak Left Ventricular Global Longitudinal Strain in Multiple Myeloma Patients: A Pilot Random Awareness Analysis. Cureus 17(3): e80509. doi:10.7759/cureus.80509 March 13, 2025.  

Overview

This study looked at heart function in patients with multiple myeloma (MM) using echocardiography. It focused on measuring left and right ventricular function in 147 MM patients at different stages of their treatment. The average age of patients was 61, with a range of 30 to 86 years. Key measurements showed that the left ventricular ejection fraction (LVEF), a common measure of heart function, was 60%, and other heart function indicators were mostly within normal ranges. However, a large number of patients with normal LVEF still had abnormal readings for peak global longitudinal strain (PGLS), a measure of how the heart muscle stretches and contracts. This study is the first to report these heart function measurements in MM patients, but more research is needed to understand how treatment affects heart health in these patients, especially before symptoms appear.

 

 

"Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment"

Source

Tasbihi K, Bruns H. Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment. Cells. 2025; 14(6):430. https://doi.org/10.3390/cells14060430. March 13, 2025. 

Overview

Despite major advances in treating multiple myeloma (MM), the disease continues to be a challenge due to drug resistance and high relapse rates. The tumor microenvironment (TME), the area surrounding the tumor, plays a critical role in treatment success and relapse. Xprovio® (selinexor) shows promise promise in treating relapsed and refractory MM. It works by blocking a protein called Exportin-1 (XPO1), which helps cancer cells survive by controlling the movement of important proteins within the cell. By disrupting this process, selinexor forces cancer cells to die. While the drug targets cancer cells directly, it is also being studied for its effects on the immune system within the TME. This review explores how selinexor may influence the immune cells in the TME, offering new insights into the development of MM and how selinexor might be used in future immune-based treatments for MM.

 

 

"The ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma"

Source

Mun Yee Koh, Tae-Hoon Chung, Nicole Xin Ning Tang, Sabrina Hui Min Toh, Jianbiao Zhou, Tze King Tan, Leilei Chen, Wee Joo Chng, Phaik Ju Teoh; The ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma. Blood 2025; 145 (11): 1164–1181. doi: https://doi.org/10.1182/blood.2024024429  March 13, 2025.

Overview

Immunomodulatory drugs (IMiDs) are important treatments for multiple myeloma (MM), but many patients develop resistance to them. While changes in a protein called cereblon are known to cause some cases of resistance, they explain only a small portion of the problem. This study discovered that another protein, adenosine deaminase acting on RNA1 (ADAR1), plays a key role in making MM cells resistant to lenalidomide, an IMiD. The researchers found that lenalidomide activates a pathway in MM cells that triggers the immune system to kill them. ADAR1 is crucial in controlling this process. When ADAR1 is removed, MM cells become more sensitive to lenalidomide, while overexpression of ADAR1 reduces sensitivity. This research highlights ADAR1's role in lenalidomide resistance and suggests that targeting ADAR1 could be a new way to improve treatment for MM patients who are resistant to this drug.

 

 

"ADAR1 in lenalidomide resistance: still immunomodulation?"

Source

Sarah Gooding; ADAR1 in lenalidomide resistance: still immunomodulation?. Blood 2025; 145 (11): 1104–1106. doi: https://doi.org/10.1182/blood.2024027539  March 13, 2025.

Overview

In a recent study, Koh et al. explored a new reason why multiple myeloma (MM) cells can become resistant to Revlimid® (lenalidomide). The researchers found that high levels of a protein called ADAR1 can make MM cells less sensitive to lenalidomide. ADAR1 affects a process called RNA editing, which prevents the immune system from detecting certain RNA molecules as foreign invaders. When ADAR1 is overactive, it reduces the immune system’s ability to fight the myeloma cells, leading to drug resistance. The study shows that targeting ADAR1 could help improve lenalidomide's effectiveness, especially in cases where the myeloma has high levels of ADAR1. This research connects immunology with cancer treatment and suggests that combining lenalidomide with ADAR1 inhibitors might be a promising strategy for treating resistant MM. However, more studies are needed to fully understand how ADAR1 and lenalidomide work together and how this can improve treatment outcomes.

 

 

"Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study"

Source

Chari, Ajai et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study. The Lancet Haematology, Volume 0, Issue 0 March 13, 2025

Overview

Talvey® (talquetamab) is a new treatment for relapsed or refractory multiple myeloma. It works by targeting two proteins (GPRC5D and CD3) to help the immune system fight the cancer. In a study, patients received talquetamab either once a week or every two weeks, and the results showed it had strong effects in patients who had already tried other treatments.

The study included 375 patients who received talquetamab. Most patients responded well to the drug, with response rates ranging from 67% to 74%, depending on the dose. Common side effects included cytokine release syndrome, changes in taste, and infections. Serious side effects, like neutropenia (low white blood cell count), were also seen but were manageable.

Talquetamab showed promise in patients who had previously received other treatments, including therapies targeting BCMA. It also had a good safety profile compared to other treatments, with fewer serious infections. The drug is being studied further in combination with other therapies.

Overall, talquetamab appears to be a promising option for patients with advanced multiple myeloma, especially those who have not responded to other treatments. However, more research is needed to confirm its long-term benefits and safety.

 

 

"Characteristics of infections after BCMA-directed CAR T-cell therapy for multiple myeloma: a real-world analysis"

Source

Tim Richardson, Daniel Schütte, Guido Kobbe, Ben-Niklas Baermann, Tobias A. W. Holderried, Friederike Schmitz, Martina Crysandt, Michael Hallek, Christoph Scheid, Udo Holtick, Oliver A. Cornely, Jannik Stemler, Sibylle C. Mellinghoff; Characteristics of infections after BCMA-directed CAR T-cell therapy for multiple myeloma: a real-world analysis. Blood Adv 2025; 9 (6): 1370–1375. doi: https://doi.org/10.1182/bloodadvances.2024015008 March 14, 2025. 

Overview

This study focused on the risk of infections in patients with relapsed/refractory multiple myeloma (RRMM) treated with BCMA-targeting CAR T-cell therapies. These therapies are known to be effective, but they come with a high risk of infections due to the immunosuppressive effects of both prior treatments and the CAR T-cell therapy itself. The study gathered real-world data from four German hospitals to understand the types, incidence, and risk factors of infections in these patients.

The results showed that infections are common, with 71.3% of patients experiencing at least one infection after CAR T-cell therapy. Bacterial infections were most frequent early on, especially during neutropenia (low white blood cell count). Gram-negative bacteria were a major cause, linked to mucosal barrier damage. Viral infections became more common after the first 30 days, accounting for 45% of all infections, with viruses like influenza and respiratory infections being the most frequent. Fungal infections were rare, which suggests that routine antifungal treatment may not be necessary.

The study also found that 33.3% of patients with infections needed to be hospitalized, and 5.3% required intensive care. Infection-related deaths accounted for 5% of the patients, which is in line with other studies on this treatment. Notably, one-third of infections could have been prevented with vaccines, such as those for the flu, pneumonia, and COVID-19. This highlights the importance of vaccination before starting CAR T-cell therapy.

The study emphasizes the need for careful infection monitoring and prevention strategies for patients undergoing CAR T-cell therapy. Improved vaccination, infection management, and better reporting of infections in clinical trials could help reduce the risks of infections and improve patient outcomes.

 

 

"Genomic characteristics and prognostic correlations in Chinese multiple myeloma patients"

Source

Chen, X., Luo, T., Zhang, W. et al. Genomic characteristics and prognostic correlations in Chinese multiple myeloma patients. BMC Med Genomics 18, 50 (2025). https://doi.org/10.1186/s12920-025-02116-5  March 14, 2025.  

Overview

While researchers have studied multiple myeloma (MM) in many populations, the genetic differences in Chinese patients are not well understood. To explore this, scientists analyzed tumor samples from 212 Chinese MM patients. They used whole-exome sequencing (WES) on 241 samples and RNA sequencing (RNA-seq) on 131 samples to compare newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM).

The study uncovered a new genetic pattern in Chinese MM patients. NDMM patients had more mutations in the NFKBIA gene compared to an international study group, along with other frequent mutations in genes like TTN, IGLL5, and SYNE1. In RRMM patients, UBR5 mutations were more common, alongside frequent mutations in OBSCN, CACNA1H, and HSPG2. Researchers also tracked genetic changes over time, providing insight into how MM evolves and spreads in the body.

The findings suggest that certain genes play a role in disease progression and survival. Mutations in RB1 and OBSCN, along with factors like age, albumin, and β2-microglobulin levels, were linked to how long patients lived without disease worsening and their overall survival. Understanding these genetic differences could help doctors predict patient outcomes and develop more personalized treatment strategies for Chinese MM patients.

 

 

"Exploring the ocular involvement in multiple myeloma: a comprehensive review of 70-year clinical studies"

Source

Ripa, M., Schipa, C., Aceto, P. et al. Exploring the ocular involvement in multiple myeloma: a comprehensive review of 70-year clinical studies. Int Ophthalmol 45, 89 (2025). https://doi.org/10.1007/s10792-025-03467-9  March 14, 2025. 

Overview

This study reviewed research on how multiple myeloma (MM) impacts eye health to determine whether these symptoms could help doctors diagnose the disease earlier. Researchers analyzed 82 studies from major medical databases, focusing on eye-related symptoms in MM patients while excluding cases caused by other conditions or treatments.

The findings suggest that eye problems may be an early sign of MM or indicate disease relapse. Reported symptoms include bruising around the eyelids, lipid deposits in the skin, drooping eyelids, and abnormal tissue growth. Some MM patients also develop crystalline deposits throughout the cornea and, in rare cases, a greenish-brown copper-like discoloration in the central cornea. Beyond the front of the eye, MM can also affect the retina and deeper eye structures, causing retinal vein blockages, fluid buildup (choroidal effusion), ciliary body cysts, and blood vessel damage (Purtscher’s retinopathy).

Because eye symptoms can appear before other MM signs, regular eye exams could help detect the disease earlier. The study emphasizes the need for close collaboration between hematologists and ophthalmologists to improve early diagnosis and treatment decisions, which may impact patient outcomes.

 

 

"Real-World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated Before the Era of Anti-CD38 Antibodies: The EMMY Cohort From 2017 to 2020"

Source

Vincent, L., Decaux, O., Perrot, A., Royer, B., Chalopin, T., Bobin, A., Macro, M., Caillot, D., Karlin, L., Jacquet, C., Sonntag, C., Mohty, M., Frenzel, L., Jaccard, A., Manier, S., Sanhes, L., Chaoui, D., Moreau, P., Garlantézec, R., Texier, N., Louni, C., Maarouf, Z., Loiseau, H.A., Hulin, C. and Merzoug, K.B. (2025), Real-World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated Before the Era of Anti-CD38 Antibodies: The EMMY Cohort From 2017 to 2020. Cancer Med, 14: e70619. https://doi.org/10.1002/cam4.70619  March 14, 2025. 

Overview

Recent advances in multiple myeloma (MM) treatment have significantly improved patient outcomes, but long-term real-world data are needed. The EMMY study, conducted in France since 2017, tracks how MM treatments are used and their impact. This report focuses on newly diagnosed MM (NDMM) patients who started treatment between 2017 and 2020.

Among 1,036 patients ineligible for stem cell transplants (NTE) (median age: 74.9 years) and 561 patients who received an autologous stem cell transplant (ASCT) (median age: 60.6 years), treatment patterns evolved over time. In ASCT patients, the preferred induction therapy shifted from Velcade® (bortezomib), Thalomid® (thalidomide), and dexamethasone (VTd) to Velcade (bortezomib), Revlimid® (lenalidomide), and dexamethasone (VRd), which became the most common choice (55.1%). Additionally, maintenance therapy with lenalidomide (R) became the standard, used in 75% of ASCT patients. For NTE patients, the use of R-based regimens increased from 29.4% in 2017 to 73.3% in 2020, with VRd use rising significantly.

Patients who received R-based treatments had better outcomes. In the ASCT group, those who received R maintenance had a median progression-free survival (mPFS) of 51.8 months, compared to 29.6 months for those without it. In NTE patients, those on R-based regimens had an mPFS of 26.3 months, while those without it had only 14.6 months. Overall, at four years, 89% of ASCT patients and 63% of NTE patients were still alive.

These findings highlight how lenalidomide-based treatments have become the standard of care for MM patients, leading to longer periods without disease progression and improved survival rates.

 

 

"Predictive and Prognostic Significance of Patient-Reported Outcomes for Survival and Adverse Events in Daratumumab-Treated Multiple Myeloma"

Source

Abuhelwa, A.Y., Almansour, S.A., Basch, E., Al-Shamsi, H.O., Abuhelwa, Z., Bustanji, Y., Semreen, M.H., Kharaba, Z., Ali, S.M., Mohamed, R., Kichenadasse, G., McKinnon, R.A., Sorich, M.J., Alzoubi, K.H. and Hopkins, A.M. (2025), Predictive and Prognostic Significance of Patient-Reported Outcomes for Survival and Adverse Events in Daratumumab-Treated Multiple Myeloma. Eur J Haematol. https://doi.org/10.1111/ejh.14410  March 14, 2025. 

Overview

Patient-reported outcomes (PROs), such as physical function and fatigue, may help predict survival in multiple myeloma (MM), but they are not widely studied. This research analyzed data from three clinical trials (MAIA, POLLUX, CASTOR) to see whether PROs could help predict treatment outcomes for MM patients receiving daratumumab-based therapy. Researchers also compared physical function with ECOG Performance Status (ECOG-PS) to see which was a better predictor of treatment response.

Among 1,804 patients, 85% provided PRO data before starting treatment. The study found that physical function, overall health, and fatigue levels were strong predictors of survival and treatment side effects. Importantly, physical function provided additional insight beyond ECOG-PS in determining which patients would benefit most from treatment. Patients with low physical function experienced the greatest benefit from daratumumab, with a 47% lower risk of death and a 70% lower risk of disease progression compared to those not receiving daratumumab. Meanwhile, patients with higher physical function had less pronounced benefits from the drug.

These findings suggest that physical function should be considered alongside ECOG-PS when deciding on treatment strategies for MM patients, particularly for daratumumab-based therapies. Using PROs in clinical decision-making could help personalize treatments and improve patient outcomes.

 

 

"Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome"

Source

Soureas, K., Malandrakis, P., Papadimitriou, MA. et al. Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome. Blood Cancer J. 15, 41 (2025). https://doi.org/10.1038/s41408-025-01248-2  March 15, 2025. 

Overview

High relapse rates and treatment resistance remain major challenges in multiple myeloma (MM). Identifying new molecular markers could help doctors better predict high-risk patients and personalize treatment. This study analyzed miRNA sequencing from MM patients and found that the miR-221/222 cluster was significantly reduced in high-risk (R-ISS III) patients compared to those in lower-risk groups (R-ISS I/II).

To confirm these findings, researchers measured miR-221/222 levels in 141 MM patients and tracked their disease progression and survival. The results were validated in two independent patient groups (149 and 86 patients), showing that patients with low miR-221/222 levels had faster disease progression and worse survival outcomes. Importantly, adding miR-221/222 loss to existing risk models improved the ability to identify high-risk patients beyond standard staging and genetic markers.

The study also found that miR-221/222 loss could predict which patients were less likely to respond well to first-line treatments. These findings suggest that testing for miR-221/222 loss could help doctors refine prognosis and personalize treatment plans, leading to better outcomes for MM patients.

 

 

"Cost-effectiveness analysis of combination therapies involving novel agents for first/second-relapse patients with multiple myeloma: a Markov model approach with calibration techniques"

Source

Wu, W., Tang, F., Wang, Y. et al. Cost-effectiveness analysis of combination therapies involving novel agents for first/second-relapse patients with multiple myeloma: a Markov model approach with calibration techniques. Health Econ Rev 15, 21 (2025). https://doi.org/10.1186/s13561-025-00611-0  March 15, 2025. 

Overview

High relapse rates and treatment resistance remain major challenges in multiple myeloma (MM). Identifying new molecular markers could help doctors better predict high-risk patients and personalize treatment. This study analyzed miRNA sequencing from MM patients and found that the miR-221/222 cluster was significantly reduced in high-risk (R-ISS III) patients compared to those in lower-risk groups (R-ISS I/II).

To confirm these findings, researchers measured miR-221/222 levels in 141 MM patients and tracked their disease progression and survival. The results were validated in two independent patient groups (149 and 86 patients), showing that patients with low miR-221/222 levels had faster disease progression and worse survival outcomes. Importantly, adding miR-221/222 loss to existing risk models improved the ability to identify high-risk patients beyond standard staging and genetic markers.

The study also found that miR-221/222 loss could predict which patients were less likely to respond well to first-line treatments. These findings suggest that testing for miR-221/222 loss could help doctors refine prognosis and personalize treatment plans, leading to better outcomes for MM patients.

 

 

"Irradiated Bone Marrow Volume is Associated With Hematologic Toxicity in Patients With Multiple Myeloma"

Source

Samuel C. Zhang, Sungjin Kim, Jennifer Steers, Bradley Stiehl, Katrina D. Silos, Giana Grigsby, Maria Oorloff, Taman Upadhaya, Robert A. Vescio, David R. Oveisi, Behrooz Hakimian, Katelyn M. Atkins, Leslie K. Ballas, Irradiated Bone Marrow Volume is Associated With Hematologic Toxicity in Patients With Multiple Myeloma, International Journal of Radiation OncologyBiologyPhysics, Volume 121, Issue 4, 2025, Pages 1026-1038, ISSN 0360-3016, https://doi.org/10.1016/j.ijrobp.2024.10.017. March 15, 2025. 

Overview

Palliative radiation therapy (RT) is often used to relieve symptoms in multiple myeloma (MM), but it can lead to low blood cell counts (cytopenia). This study explored whether the amount of bone marrow exposed to radiation (BMV10Gy) is linked to the risk of blood-related side effects (hematologic toxicity, HT) in MM patients.

Researchers analyzed 125 MM patients who received palliative RT between 2007 and 2023. They tracked blood levels before, during, and after RT to see if patients developed severe blood cell loss requiring transfusions, hospitalizations, or treatment delays.

Results showed that patients with higher bone marrow exposure to radiation (BMV5-15Gy) were more likely to develop blood-related side effects. Patients who had received three or more prior treatments for MM were at the highest risk—nearly 10 times more likely to experience HT than newly diagnosed patients.

This study is the first to link bone marrow radiation exposure to HT in MM patients. The findings suggest that careful radiation planning is essential, especially for patients with extensive prior treatments or weakened bone marrow reserves.

 

 

"Beyond the Marrow–Moving Toward a Systemic Perspective of Radiation-Induced Cytopenias"

Source

Sabrina L. Browning, Mendez Lourdes, Natalia Neparidze, Timothy J. Robinson, Beyond the Marrow–Moving Toward a Systemic Perspective of Radiation-Induced Cytopenias, International Journal of Radiation OncologyBiologyPhysics, Volume 121, Issue 4, 2025, Pages 1039-1041, ISSN 0360-3016, https://doi.org/10.1016/j.ijrobp.2024.11.100. March 15, 2025. 

Overview

This study provides new insights into how radiation therapy (RT) affects blood cell production in multiple myeloma (MM) patients. Experts believe this is just the beginning of a deeper understanding of how radiation impacts bone marrow health. Radiation can trigger inflammation and immune system changes by increasing levels of cytokines, such as IL-6, which may contribute to blood cell loss. Chronic exposure to these inflammatory signals can further disrupt bone marrow function, worsening radiation-related blood toxicities.

Some MM patients already have immune-related blood cell disorders, like immune thrombocytopenic purpura (low platelets) or immune neutropenia (low white blood cells). This may be due to interactions between cancerous plasma cells and bone marrow cells, possibly influenced by high levels of cytokines such as IL-6, IL-18, and CXCL9. Many MM patients also have clonal hematopoiesis (CH), a condition where genetic mutations cause abnormal blood cell production. CH is linked to higher IL-6 levels and a worse prognosis. Since CH is common in MM, it may increase the risk of radiation-related blood toxicities.

This study is the first to measure how radiation exposure affects blood cells in MM patients. Future research should explore how cytokines, genetic changes, and bone marrow characteristics influence radiation-related blood toxicities to help guide safer, more personalized treatments.

 

 

"BCL2 inhibition for multiple myeloma and AL amyloidosis"

Source

Cani L, Gupta VA, Kaufman JL. BCL2 inhibition for multiple myeloma and AL amyloidosis. Br J Haematol. 2025; 00: 1–12. https://doi.org/10.1111/bjh.20046  March 16, 2025. 

Overview

Multiple myeloma (MM) and light-chain (AL) amyloidosis remain incurable, even with new treatments. Researchers are exploring a class of drugs called BCL2 inhibitors to help fight these diseases.

Venetoclax, the most studied BCL2 inhibitor, was originally developed for other blood cancers. However, studies show it can also help patients with MM and AL amyloidosis, especially those with a specific genetic feature called t(11;14). Venetoclax has been effective both on its own and when combined with other treatments, but doctors need to be cautious about side effects and ensure the right dose for each patient.

Other BCL2-targeting drugs are also being tested in clinical studies. Sonrotoclax is showing promise for MM, while Zn-d5 and Lisaftoclax may help treat AL amyloidosis. These new drugs could expand treatment options for patients in the future.

 

 

"Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma"

Source

Sha Ma, Jieyun Xia, Miao Zhang, Wenyu Li, Meng Xiao, Yuqian Sha, Wenya Wang, Jianteng Zhou, Ying Wang, Kunming Qi, Chunling Fu, Zengtian Sun, Dian Zhou, Qian Sun, Tingting Qiu, Zhiling Yan, Feng Zhu, Wei Chen, Hai Cheng, Wei Sang, Jiang Cao, Depeng Li, Zhenyu Zhen Li, Mariateresa Fulciniti, Yao Yao, Kailin Xu, Mingshan Niu; Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma. Blood 2025; blood.2024026622. doi: https://doi.org/10.1182/blood.2024026622  March 16, 2025. 

Overview

GPRC5D is a promising target for CAR T-cell therapy in multiple myeloma (MM), but many patients still relapse after treatment. Scientists wanted to understand why this happens, so they analyzed MM samples from 10 patients who relapsed after receiving GPRC5D CAR T therapy.

They found that 8 patients lost GPRC5D expression entirely, while 2 had mixed expression (some cells with and some without GPRC5D). In 3 cases, genetic changes caused this loss—either complete deletions of the GPRC5D gene or its regulatory regions. However, most cases (7 out of 10) showed no genetic mutations. Instead, in 5 cases, researchers discovered increased DNA methylation (a chemical change that silences genes) in areas controlling GPRC5D expression.

Further lab tests confirmed that when GPRC5D was highly methylated, its expression dropped. However, treating myeloma cells with azacitidine, a drug that reverses methylation, restored GPRC5D levels.

These findings suggest that myeloma cells can resist GPRC5D CAR T therapy by either deleting the gene or silencing it through DNA methylation. This discovery could help doctors develop better strategies to prevent relapse.

 

 

"Loss of BCL7A Permits IRF4 Transcriptional Activity and Cellular Growth in Multiple Myeloma"

Source

Chandraditya Chakraborty, Srikanth Talluri, Moritz Binder, Eugenio Morelli, Jessica Encinas Mayoral, Sanika Derebail, Anil Aktas Samur, Charles B. Epstein, Kenneth C. Anderson, Masood A Shammas, Mehmet K. Samur, Mariateresa Fulciniti, Nikhil C. Munshi; Loss of BCL7A Permits IRF4 Transcriptional Activity and Cellular Growth in Multiple Myeloma. Blood 2025; blood.2024026588. doi: https://doi.org/10.1182/blood.2024026588  March 16, 2025.

Overview

Multiple myeloma (MM) is a complex blood cancer with many genetic changes, but no single mutation is found in most patients. However, researchers have discovered that a specific region of the BCL7A gene is mutated in 62% of MM patients. This mutation leads to a loss of BCL7A expression, which is much lower in MM cells compared to normal plasma cells.

Lab studies showed that when BCL7A is missing, myeloma cells grow and spread more quickly. On the other hand, restoring BCL7A reduced their survival, suggesting that BCL7A acts as a tumor suppressor—a gene that normally helps keep cancer growth in check.

Further research revealed that BCL7A interacts with IRF4, a key protein that drives myeloma cell survival. BCL7A helps limit IRF4’s activity, but when BCL7A is lost, IRF4 becomes more active, increasing the production of certain cytokines (cell-signaling proteins) that fuel myeloma growth. At the same time, BCL7A loss reduces mitochondrial metabolism and ROS (reactive oxygen species) levels, which helps myeloma cells survive longer.

This study highlights BCL7A as a potential target for future treatments, offering new insights into how myeloma develops and persists.

 

 

"Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma"

Source

Jiang, F., Zhang, Y., Peng, F. et al. Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma. J Transl Med 23, 338 (2025). https://doi.org/10.1186/s12967-025-06319-3  March 16, 2025. 

Overview

Bone damage, or myeloma bone disease (MBD), is one of the most common complications of multiple myeloma (MM). Researchers have discovered that a protein called complement C3a plays a key role in worsening bone loss by activating osteoclasts, the cells that break down bone. However, the exact process behind this remained unclear.

This study found that Sirt1, a protein that helps regulate bone metabolism, is lower in MM patients with MBD. The researchers also found that higher levels of C3a were linked to lower Sirt1 levels and more severe bone loss. Further experiments showed that Sirt1 normally helps prevent excessive bone breakdown, but C3a blocks this protective effect, leading to increased osteoclast activity and worsening bone disease.

The researchers tested a Sirt1-activating drug (SRT1720) in lab-grown bone cells and a mouse model of MBD. They found that activating Sirt1 reduced osteoclast activity, slowed bone damage, and counteracted the harmful effects of C3a.

This study suggests that boosting Sirt1 activity could be a new way to treat MBD and protect bones in MM patients. By targeting the C3a-Sirt1 pathway, doctors may be able to slow bone loss and improve bone health in people with MM.

 

 

"Unveiling cardiovascular and respiratory toxicities with monoclonal antibodies in multiple myeloma: disproportionality analysis from the FDA Adverse Event Reporting System"

Source

Barbieri, M.A., Russo, G., Cicala, G. et al. Unveiling cardiovascular and respiratory toxicities with monoclonal antibodies in multiple myeloma: disproportionality analysis from the FDA Adverse Event Reporting System. Eur J Clin Pharmacol (2025). https://doi.org/10.1007/s00228-025-03824-8  March 17, 2025.  

Overview

Monoclonal antibodies (mAbs) have transformed multiple myeloma (MM) treatment, offering powerful anti-cancer effects. However, like all medications, they can cause side effects. This study analyzed safety data from 2015 to 2023 to identify unexpected heart (cardiovascular) and lung (respiratory) complications linked to mAbs used in MM treatment, including daratumumab, elotuzumab, isatuximab, elranatamab, belantamab mafodotin, teclistamab, and talquetamab.  

The findings showed that some patients—mostly older adults—experienced serious side effects. Daratumumab was linked to heart failure, blood clots such as pulmonary embolism and deep vein thrombosis, and respiratory failure. Isatuximab was associated with irregular heartbeats (atrial fibrillation), blood clots, and pulmonary embolism, while elotuzumab was tied to atrial fibrillation and deep vein thrombosis. These risks had not been widely reported before, highlighting the importance of continued drug safety monitoring.  

Patients receiving mAb therapy for MM should be closely watched for heart and lung complications, especially those at higher risk. This research underscores the need for careful patient selection and early detection of potential side effects to ensure the safest possible treatment.

 

 

"PGV001, a multi-peptide personalized neoantigen vaccine platform: Phase I study in patients with solid and hematological malignancies in the adjuvant setting"

Source

Mansi Saxena, Thomas U. Marron, Julia Kodysh, John P. Finnigan, Sayali Onkar, Anna Kaminska, Kevin Tuballes, Ruiwei Guo, Rachel Lubong. Sabado, Marcia Meseck, Timothy J. O'Donnell, Robert P. Sebra, Samir Parekh, Matthew D. Galsky, Ana Blasquez, Gustavo Gimenez, Mesude Bicak, Cansu Cimen Bozkus, Daniela Delbeau-Zagelbaum, Denise Rodriguez, Ana Acuna-Villaorduna, Krzysztof J. Misiukiewicz, Marshall R. Posner, Brett A. Miles, Hanna Y. Irie, Amy Tiersten, Deborah B. Doroshow, Andrea Wolf, John Mandeli, Rachel Brody, Andres M. Salazar, Sacha Gnjatic, Jeff Hammerbacher, Eric Schadt, Philip Friedlander, Alexander Rubinsteyn, Nina Bhardwaj; PGV001, a multi-peptide personalized neoantigen vaccine platform: Phase I study in patients with solid and hematological malignancies in the adjuvant setting. Cancer Discov 2025; https://doi.org/10.1158/2159-8290.CD-24-0934  March 17, 2025.   

Overview

Immunotherapies like immune checkpoint inhibitors have improved cancer treatment, but not all patients respond to them. One reason is that some patients lack the right immune cells to attack their cancer. To address this, researchers developed a personalized cancer vaccine called PGV001, which uses a patient’s own tumor mutations (neoantigens) to stimulate an immune response.

In a clinical trial, PGV001 was given to 14 patients with high-risk cancers, including solid tumors and blood cancers. The vaccine targeted up to 10 neoantigens per patient and was well tolerated, with 13 patients receiving it and 11 completing the treatment. All vaccinated patients developed immune responses, showing that this approach can help the body recognize and fight cancer. These results suggest that personalized cancer vaccines like PGV001 could be a promising way to boost the immune system and improve treatment outcomes.

 

 

"Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma"

Source

Yan, S., Ming, X., Zheng, R., Zhu, X. and Xiao, Y. (2025), Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma. Cancer Med, 14: e70764. https://doi.org/10.1002/cam4.70764  March 17, 2025. 

Overview

Targeted therapy is an important treatment approach for multiple myeloma, especially for patients whose disease has returned or stopped responding to standard treatments. In recent years, therapies that target specific proteins on mature B cells have provided new hope for these patients. As more people receive these treatments, switching to a different target may be a useful strategy when the disease relapses.

One promising target is GPRC5D, a protein found on the surface of myeloma cells. Researchers are actively studying therapies that attack this protein to help patients with relapsed or treatment-resistant multiple myeloma. This review highlights the latest advancements in GPRC5D-targeted treatments, offering insights that could guide future research and improve treatment options.

 

 

 

"The value of multiparametric functional MRI histogram features in assessing multiple myeloma activity"

Source

Lin, Y., Huang, H., Xiao, Z. et al. The value of multiparametric functional MRI histogram features in assessing multiple myeloma activity. Eur Radiol (2025). https://doi.org/10.1007/s00330-025-11507-2 March 18, 2025. 

Overview

Researchers are exploring new imaging techniques to assess disease activity in multiple myeloma. This study examined the effectiveness of different imaging features, including apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), and fat fraction (FF), in evaluating myeloma progression.  

The study included 24 patients who underwent advanced imaging scans between April and December 2023. Researchers analyzed specific histogram features from these scans and found that while ADC and MD did not correlate with disease activity, MK and FF features were significantly linked to multiple myeloma status. Among these, MK_InterquartileRange and FF_Median were the most effective in assessing disease activity.  

These findings suggest that MK and FF imaging features could be valuable tools for monitoring multiple myeloma progression, potentially helping doctors make more precise treatment decisions.

 

 

"Establishing a successful outpatient CAR T-Cell program with cilta-cel: real-world experience from an expert roundtable"

Source

Alsina M, Dhakal B, Pantin J, Huff CA, Janakiram M. Establishing a successful outpatient CAR T-Cell program with cilta-cel: real-world experience from an expert roundtable. Future Oncol. 2025 Mar 18:1-8. doi: 10.1080/14796694.2025.2476382. Epub ahead of print. March 18, 2025. 

Overview

CAR T-cell therapy has quickly advanced, moving into earlier treatment stages and shifting from hospital stays to outpatient care. To meet rising patient demand, many institutions have developed outpatient CAR-T programs, which help conserve resources, expand treatment access, reduce hospital time, and lower costs.  

Ciltacabtagene autoleucel (cilta-cel), a CAR-T therapy for relapsed or refractory multiple myeloma, is well-suited for outpatient administration due to its predictable side effect timeline. Its delayed onset of cytokine release syndrome and neurotoxicity allows for careful monitoring outside of a hospital setting. As myeloma treatment evolves and hospital space remains limited, outpatient cilta-cel programs offer a practical and cost-effective solution that aligns with patient preferences.  

To support the growth of these programs, a panel of myeloma and cellular therapy experts shared their real-world experiences. Their discussion covered key factors for success, including patient and caregiver preparation, safety considerations, and logistical planning. These insights can help more clinics establish outpatient CAR-T programs, improving access to this life-saving treatment.

 

 

"Global, regional, and national multiple myeloma burden from 1990 to 2021: a systematic analysis for of the Global Burden of Disease Study 2021"

Source

Diao, X., Ben, T., Cheng, S. et al. Global, regional, and national multiple myeloma burden from 1990 to 2021: a systematic analysis for of the Global Burden of Disease Study 2021. BMC Public Health 25, 1054 (2025). https://doi.org/10.1186/s12889-025-22240-2  March 19, 2025

Overview

Multiple myeloma (MM) is the second most common type of blood cancer worldwide, but there hasn't been a comprehensive global analysis of the disease's impact across different regions and time periods. This study aimed to examine MM's incidence, death rates, and disability-adjusted life years (DALYs) from 1990 to 2021, focusing on how these factors vary by age and region.

The analysis used data from 204 countries and territories, breaking down the incidence, mortality, and DALYs by age, sex, and region to better understand trends. The results showed that in 2021, there were around 35,000 new MM cases globally, with China and Germany having the highest numbers. Europe had the highest incidence rates, while North America had the highest death rates and DALYs. Overall, the rates of new cases, deaths, and DALYs increased between 1990 and 2021, with men being more affected than women. The study also found that wealthier regions had higher rates of MM.

These findings highlight the growing global burden of MM, with significant regional differences. They emphasize the need for targeted prevention efforts and new treatments to reduce the disease's impact and improve patient outcomes.

 

 

"Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients"

Source

Morabito, F., Martino, E.A., Galli, M., Offidani, M., Zambello, R., Bringhen, S., Giuliani, N., Califano, C., Brunori, M., Gagliardi, A., Sgherza, N., Quinto, A.M., Barilà, G., Belotti, A., Cerchione, C., Casaluci, G.M., Fontana, R., Bongarzoni, V., Tarantini, G., Derudas, D., Patriarca, F., Gozzetti, A., Sementa, A., Antonioli, E., Rago, A., Lotti, F., De Magistris, C., Petrucci, M.T., Pettine, L., Bolli, N., Conticello, C., Zamagni, E., Palmieri, S., Musso, M., Mele, A., Pepa, R.D., Vigna, E., Bruzzese, A., Fazio, F., Mina, R., Paris, L., Vincelli, I.D., Farina, G., Cangialosi, C., Mancuso, K., Falcone, A.P., Mele, G., Sica, A., Morè, S., Reddiconto, G., Tripepi, G., D'Arrigo, G., Barbieri, E., Quaresima, M., Cartia, C.S., Pezzatti, S., Marcatti, M., Farina, F., Cafro, A., Palumbo, M., Masoni, V., Ferretti, V.V., Di Raimondo, F., Musto, P., Neri, A., Mangiacavalli, S. and Gentile, M. (2025), Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients. Eur J Haematol. https://doi.org/10.1111/ejh.14413  March 19, 2025. 

Overview

This study focused on the effects of certain genetic changes in patients with relapsed or refractory multiple myeloma (RRMM) who were treated with a combination of Darzalex®  (daratumumab), Empliciti®  (elotuzumab), and Kyprolis®  (carfilzomib). Specifically, the researchers looked at abnormalities involving the gain or amplification of chromosome 1q (+1q), which are linked to poorer outcomes.

The study found that patients with these +1q abnormalities had lower response rates to treatment and shorter progression-free survival (PFS) compared to those without these abnormalities. On average, patients with +1q gain had a PFS of 8 months, and those with +1q amplification had a PFS of 7.4 months, while patients without these abnormalities had a PFS of 28 months. Additionally, overall survival (OS) was also lower in patients with +1q abnormalities. Those with +1q gain had an OS of 25 months, and those with +1q amplification had an OS of 19.5 months, compared to 42.2 months for those without +1q abnormalities.

The study concluded that +1q abnormalities are strong predictors of worse outcomes in RRMM. These genetic changes, along with other high-risk factors, should be considered when determining a patient’s prognosis and treatment plan. The findings highlight the importance of detailed genetic testing to guide personalized treatments for RRMM patients.

 

 

"An analysis of the clinical value of CHI3L1 as a biomarker of multiple myeloma progression"

Source

Tang L, Liang J, Huang Y, Guo K, Huang Y, He Y, Wang J, Lei M. An analysis of the clinical value of CHI3L1 as a biomarker of multiple myeloma progression. Clin Immunol. 2025 Mar 19:110474. doi: 10.1016/j.clim.2025.110474. Epub ahead of print.  March 19, 2025. 

Overview

This study explored the role of a protein called Chitinase 3-like protein-1 (CHI3L1) in multiple myeloma (MM) and its potential as a biomarker for predicting disease progression. The researchers compared the levels of CHI3L1 in the blood of 136 MM patients, dividing them into two groups: those with non-progressing MM and those with progressing MM. They found that CHI3L1 levels were significantly higher in MM patients compared to healthy controls, and that patients with advanced stages of MM had higher levels of CHI3L1.

The results showed that higher levels of CHI3L1 were strongly linked to disease progression. Patients with higher CHI3L1 levels had a 243.6% increased risk of progression compared to those with lower levels. The study concluded that CHI3L1 could be a useful marker for assessing disease severity in MM patients and predicting the likelihood of disease progression, suggesting its potential use in guiding treatment decisions and monitoring prognosis.

 

 

"NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma"

Source

Sojeong Kim, Jeong-Eun Kwak, June-Young Koh, Ji Eun Lee, Hye Won Kook, Minchae Kim, Haerim Chung, Yuri Kim, Soo Jeong Kim, Jin Seok Kim, June-Won Cheong, Min Goo Lee, Hoyoung Lee, Su-Hyung Park, Eui-Cheol Shin, Saeam Shin, Sun Och Yoon, Il-Kyu Choi, Jeong Seok Lee, Hyunsoo Cho; NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma. Blood 2025; blood.2024025875. doi: https://doi.org/10.1182/blood.2024025875  March 19, 2025

Overview

Recent research shows that CD4+ T cells, traditionally known for their roles in helping or regulating the immune system, may also play a direct part in fighting cancer. This study looked at CD4+ T cells from the bone marrow of patients with multiple myeloma at different stages of the disease. Using advanced techniques like single-cell RNA sequencing, the researchers found a special group of CD4+ T cells, called CD4+ cytotoxic T lymphocytes (CTLs), that were more common and expanded in myeloma patients. These CD4+ CTLs were able to directly attack and kill myeloma cells, a process that was blocked when a specific protein (NKG2D) was inhibited.

The study also revealed that higher levels of these NKG2D+ CD4+ CTLs were linked to better survival in patients. This suggests that targeting these CD4+ CTLs could offer new ways to improve immunotherapy for multiple myeloma patients, providing hope for better treatment outcomes.

 

 

"A systematic review and meta-analysis of phase III randomized controlled trials to assess the risk of pneumonia, URTIs, and VTE in multiple myeloma patients treated with isatuximab"

Source

Jones DT, Aboaid H, Srinivasmurthy R, Nguyen K, Nanda RK, Ta J, Chuang BT, Myat YM, Hanspal A, Thein KZ, Htut TW. A systematic review and meta-analysis of phase III randomized controlled trials to assess the risk of pneumonia, URTIs, and VTE in multiple myeloma patients treated with isatuximab. Explor Target Antitumor Ther. 2025 Mar 19;6:1002300. doi: 10.37349/etat.2025.1002300.  March 19, 2025. 

Overview

This study looks at the risks of pneumonia, upper respiratory tract infections (URTIs), and venous thromboembolism (VTE) in multiple myeloma (MM) patients treated with Sarclisa®  (isatuximab), a monoclonal antibody that targets the CD38 protein on myeloma cells. Isatuximab has been shown to improve treatment outcomes, but it can also cause certain side effects. The research reviewed data from several large clinical trials to determine how often these infections and complications occur in patients treated with isatuximab.

The results showed that patients who received isatuximab had a higher rate of pneumonia compared to those who did not, with both overall and high-grade pneumonia being more common in the isatuximab group. However, there were no significant differences in the rates of URTIs or VTE between the two groups. This finding suggests that while isatuximab can improve treatment effectiveness, it also increases the risk of pneumonia. The study emphasizes the need for careful monitoring, antibiotic prevention, and measures to reduce blood clot risks in patients receiving this treatment.

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"Extramedullary Multiple Myeloma: Challenges and Opportunities"

Source

Ho M, Paruzzo L, Minehart J, Nabar N, Noll JH, Luo T, Garfall A, Zanwar S. Extramedullary Multiple Myeloma: Challenges and Opportunities. Current Oncology. 2025; 32(3):182. https://doi.org/10.3390/curroncol32030182  March 20, 2025. 

Overview

Extramedullary multiple myeloma (EMM) is a form of multiple myeloma where cancerous cells spread outside the bone marrow to soft tissues. It is an aggressive disease, often linked to high-risk genetic factors and early relapses, which leads to shorter survival times, even with the use of modern immunotherapies. Researchers are still studying the molecular and environmental factors that contribute to EMM, aiming to develop better treatments. This review discusses what we know so far about the biology of EMM and its differences from regular multiple myeloma. It also covers current treatment options, noting that there is a lack of large, randomized studies focusing on this specific group of patients.

 

 

"Real-world effectiveness of ixazomib, lenalidomide and dexamethasone in Asians with relapsed/refractory multiple myeloma"

Source

Ng, S.C., Moon, JH., Park, S.S. et al. Real-world effectiveness of ixazomib, lenalidomide and dexamethasone in Asians with relapsed/refractory multiple myeloma. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-03927-z March 20, 2025. 

Overview

The APEX study evaluated the effectiveness and safety of the combination treatment ixazomib, lenalidomide, and dexamethasone (IRd) in Asian patients with relapsed/refractory multiple myeloma (RRMM). This study included 104 patients from South Korea, Malaysia, and Thailand, with a median age of 64. The main results showed that the median time to next treatment was 32.1 months, and 72.1% of patients responded to the treatment. The median progression-free survival was 27.7 months, and overall survival data was still being collected. Elderly patients (ages 65 and older) had better outcomes compared to the overall group. Most patients (90.4%) experienced side effects, with pneumonia, neutropenia, and gastroenteritis being the most common severe reactions. The study confirms that IRd is both safe and effective in real-world settings in Asia, particularly for older patients, and its results are consistent with other studies.

 

 

"Dual CARM1-and IKZF3-targeting: A novel approach to multiple myeloma therapy"

Source

Wei Ni, Swati Garg, Basudev Chowdhury, Martin Sattler, Dana Sanchez, Chengcheng Meng, Taisei Akatsu, Katherine A. Donovan, Jun Qi, Michelle Y. Wang, Cara Ann Starnbach, Xiaoxi Liu, Maria Tarazona Guzman, Wei Pin Teh, Richard Stone, James D. Griffin, Sara Buhrlage, Ellen Weisberg, Dual CARM1-and IKZF3-targeting: A novel approach to multiple myeloma therapy, Molecular Therapy Oncology, Volume 33, Issue 1, 2025, 200952, ISSN 2950-3299, https://doi.org/10.1016/j.omton.2025.200952. March 20, 2025

Overview

Recent research has shown that targeting CARM1, a protein crucial for the survival of multiple myeloma (MM) cells, could be a promising strategy for treating MM, including cases resistant to standard treatments. Scientists developed a new compound called 074, which combines a CARM1 inhibitor with the immunomodulatory drug pomalidomide (IMiD). This combination was found to kill MM cells more effectively than either treatment alone, even overcoming resistance to IMiDs. The compound works by downregulating important proteins like MYC and IKZF3, which are essential for MM cell survival. Importantly, 074 showed limited toxicity to normal cells, making it a potentially safer option. This approach could be particularly useful for treating IMiD-resistant MM, offering a new direction for improving patient outcomes. Further studies are needed to optimize 074 for use in clinical settings.

 

 

"Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial"

Source

Manier S, Dimopoulos M-A, Leleu XP, Moreau P, Cavo M, Goldschmidt H, Orlowski RZ, Tron M, Tekle C, Brégeault M-F, Shafer AT, Beksac M, Facon T. Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial. Haematologica; https://doi.org/10.3324/haematol.2024.287200 [Early view]. March 20, 2025. 

Overview

In a study called IMROZ, researchers looked at the effects of adding Sarclisa® (isatuximab, or Isa) to a combination treatment (VRd) in patients with newly diagnosed multiple myeloma who are not eligible for a stem cell transplant. They divided patients into frail and non-frail groups using a frailty score. A total of 26.7% of patients were considered frail, and 72.0% were non-frail. The results showed that adding Isa to VRd significantly improved progression-free survival for both frail and non-frail patients. Frail patients who received Isa-VRd also had higher rates of achieving minimal residual disease negativity and complete response. Overall, Isa-VRd was found to be effective with a manageable safety profile, making it a good treatment option for frail patients.

 

 

"Clonal hematopoiesis is clonally unrelated to multiple myeloma and is associated with specific microenvironmental changes"

Source

Marta Lionetti, Margherita Scopetti, Antonio Matera, Akihiro Maeda, Alessio Marella, Francesca Lazzaroni, Giancarlo Castellano, Sonia Fabris, Stefania Pioggia, Silvia Lonati, Alfredo Marchetti, Alessandra Cattaneo, Marta Tornese, Antonino Neri, Claudia Leoni, Loredana Pettine, Valentina Traini, Ilaria Silvestris, Marzia Barbieri, Giuseppina Fabbiano, Domenica Ronchetti, Elisa Taiana, Claudio De Magistris, Matteo Claudio Da Via', Francesco Passamonti, Niccolò Bolli; Clonal hematopoiesis is clonally unrelated to multiple myeloma and is associated with specific microenvironmental changes. Blood 2025; blood.2024026236. doi: https://doi.org/10.1182/blood.2024026236  March 20, 2025.  

Overview

In multiple myeloma (MM), the disease's progression from a mild, early stage to an aggressive form is influenced not only by genetic changes but also by the tumor microenvironment (TME). One factor, called clonal hematopoiesis of indeterminate potential (CHIP), is common in hematopoietic stem cells and is linked to a more inflamed TME. In a study of 106 MM patients, researchers found that CHIP often coexists with MM at diagnosis, especially in older patients and those with more advanced disease. They discovered that CHIP changes the TME by reducing the number of naïve T cells, promoting inflammation, and impairing immune cell functions. These changes help MM cells survive and evade the immune system. This study shows that CHIP influences the TME of MM, potentially leading to a worse outcome, and suggests that further research is needed to better understand this relationship.

 

 

"NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma"

Source

Gunnell A, Kimber ST, Houlston R, Kaiser M. NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma. Oncotarget. 2025 Mar 21;16:220-229. doi: 10.18632/oncotarget.28706.  March 21, 2025. 

Overview

In multiple myeloma (MM), the overexpression of a protein called NSD2, which occurs due to a specific genetic change (t(4;14)), plays a key role in the development of the disease. Researchers studied the effects of NSD2 overexpression in MM cells using a cell line called KMS11 and a version of the cell line with NSD2 removed. They found that NSD2 significantly impacts gene expression and DNA organization, affecting genes that control cell identity. One key finding was that NSD2 overexpression lowered the levels of CD38, a marker commonly found on plasma cells, suggesting a change in the cell's surface characteristics. However, important plasma cell genes like PRDM1, IRF4, and XBP1 were not affected. These results suggest that NSD2 helps maintain the identity of MM cells, which could lead to new treatment strategies targeting NSD2 in the future.

 

 

"Bone Marrow-Targeted Liposomes Loaded with Bortezomib Overcome Multiple Myeloma Resistance. ACS Nano"

Source

Menachem R, Nudelman I, Vorontsova A, Livneh I, Sela M, Benguigui M, Manobla B, Shammai Y, Deo A, Buxbaum C, Bessler R, Raviv Z, Shklover J, Sznitman J, Ciechanover A, Schroeder A, Shaked Y. Bone Marrow-Targeted Liposomes Loaded with Bortezomib Overcome Multiple Myeloma Resistance. ACS Nano. 2025 Mar 21. doi: 10.1021/acsnano.4c10597. Epub ahead of print.  March 21, 2025. 

Overview

Multiple myeloma (MM) can be difficult to treat because it keeps progressing and may be resistant to some treatments. While Velcade® (bortezomib), a proteasome inhibitor, has been an important treatment, MM often becomes aggressive and resistant to it. To address this, researchers developed a new treatment called AMD3100-targeted Bortezomib Liposomes (ATBL). This treatment targets MM cells more directly, allowing for better delivery of bortezomib to those cells. In both lab tests and mice, ATBL worked better than regular bortezomib or non-targeted treatments. It was especially effective against MM that was resistant to bortezomib. The treatment’s success was linked to a protein called CXCR4, which helps the cells take in ATBL. This suggests that measuring CXCR4 levels could help predict which patients would benefit most from this treatment. Importantly, ATBL also showed a good safety profile and could target bone marrow effectively. This research points to ATBL as a promising new therapy for MM, especially for cases resistant to current treatments.

 

 

"CAR-T cell therapy for patients with extramedullary multiple myeloma: opportunities and challenges"

Source

Yin Wang, Xiaoli Hu, Juan Du, Bei Liu, CAR-T cell therapy for patients with extramedullary multiple myeloma: opportunities and challenges, European Journal of Cancer, 2025, 115374, ISSN 0959-8049, https://doi.org/10.1016/j.ejca.2025.115374. March 21, 2025. 

Overview

With multiple myeloma (MM), abnormal plasma cells grow, usually in the bone marrow. However, some of these cells can grow outside of the bone marrow, which is called extramedullary disease (EMD). Although treatments like proteasome inhibitors, immunomodulators, monoclonal antibodies, and stem cell transplants have improved survival for many MM patients, those with EMD still have a worse prognosis. There are currently no specific treatments for EMD. Chimeric antigen receptor T (CAR-T) cell therapy, a new type of immunotherapy, has been successful for many MM patients and might offer hope for those with EMD in the future. This review looks at the mechanisms behind EMD and the potential for CAR-T therapy to treat it, hoping to provide insights into future treatment options for EMD.

 

 

"Doxorubicin PK/PD modeling in multiple myeloma: towards in silico trials"

Source

Andrean, D., Da Ros, F., Mazzucato, M. et al. Doxorubicin PK/PD modeling in multiple myeloma: towards in silico trials. Biol Direct 20, 33 (2025). https://doi.org/10.1186/s13062-025-00626-x  March 21, 2025. 

Overview

Doxorubicin (DOXO) is a chemotherapy drug commonly used to treat Multiple Myeloma (MM), a blood cancer that can be managed but not cured. Researchers have developed a tool to improve DOXO treatment in MM by creating a simulation that combines both pharmacokinetics (how the drug moves in the body) and pharmacodynamics (how the drug affects the body). This model helps understand how DOXO works at different dosages, frequencies, and treatment durations. By using both lab experiments and modeling techniques, the researchers linked the drug's movement and effects on MM cells, allowing them to test various treatment plans and find the most effective options for MM patients.

 

 

"PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of atezolizumab for alveolar soft part sarcoma, epcoritamab for follicular lymphoma, and isatuximab for multiple myeloma in Japan"

Source

Matsumura, N., Mandai, M. PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of atezolizumab for alveolar soft part sarcoma, epcoritamab for follicular lymphoma, and isatuximab for multiple myeloma in Japan. Int J Clin Oncol (2025). https://doi.org/10.1007/s10147-025-02741-1  March 21, 2025.   

Overview

On February 20, 2025, the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan approved several new anticancer drugs. Atezolizumab, an anti-PD-L1 antibody, was approved for the treatment of unresectable alveolar soft part sarcoma, showing a 10% overall response rate in a trial with 20 patients. Epcoritamab, a bispecific antibody targeting CD3 and CD20, was approved for relapsed or refractory follicular lymphoma (grade 1-3A), with an impressive 82% overall response rate in the clinical trials, and 95.2% in Japanese patients. Isatuximab, an anti-CD38 antibody, was approved for multiple myeloma, showing improved progression-free survival when added to a combination therapy of bortezomib, lenalidomide, and dexamethasone, with a hazard ratio of 0.60. In January 2025, the PMDA also directed a revision to the package inserts of some drugs, including pembrolizumab, to include a warning for the risk of pancreatic exocrine insufficiency based on post-marketing safety data.

 

 

"VRd vs. VPd as induction therapy in high risk newly diagnosed multiple myeloma"

Source

Li, C.Y., Zhong, L., Chen, D.G. et al. VRd vs. VPd as induction therapy in high risk newly diagnosed multiple myeloma. Sci Rep 15, 9946 (2025). https://doi.org/10.1038/s41598-025-85398-0  March 22, 2025. 

Overview

Researchers compared two drug combinations for newly diagnosed high-risk multiple myeloma: VPd (bortezomib, pomalidomide, and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone). They analyzed the treatment responses of 46 patients who received one of these regimens between 2021 and 2023. After four cycles, the overall response rate was 100% for VPd and 92% for VRd. More patients achieved a very good partial response (VGPR) or better with VPd (90%) than with VRd (52%), suggesting that VPd may provide a deeper response. However, VPd was also linked to a higher risk of skin rash.

Despite differences in response rates, survival outcomes were similar between the two groups. The average overall survival was 27 months for VRd and 21 months for VPd, while progression-free survival was 27 months and 20 months, respectively. These differences were not statistically significant.

The study highlights VPd as a promising first-line treatment for high-risk multiple myeloma, potentially offering stronger responses than VRd. However, further research is needed to confirm these results and assess the long-term benefits and risks of VPd.

 

 

"Impact of daratumumab on the development of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma"

Source

Minakata, D., Fujiwara, Si., Honda, S. et al. Impact of daratumumab on the development of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02558-6  March 23, 2025. 

Overview

Researchers studied whether receiving daratumumab before an autologous stem cell transplant (ASCT) affects the risk of engraftment syndrome (ES) in people with newly diagnosed multiple myeloma. Engraftment syndrome is a complication that can occur during the recovery phase after ASCT, causing symptoms like fever, diarrhea, rash, lung issues, and liver problems. While daratumumab has been shown to improve progression-free survival (PFS) when added to myeloma treatment, its impact on ASCT-related side effects remains unclear.

The study analyzed multiple myeloma patients who underwent ASCT at Jichi Medical University between 2013 and 2023. Researchers tracked cases of ES using established medical criteria. Most patients received bortezomib-based induction therapy before ASCT, and since 2019, those who did not achieve measurable residual disease (MRD) negativity received additional treatment with daratumumab-based therapy before their transplant. Stem cells were collected using growth factor treatments, and high-dose melphalan chemotherapy was given before ASCT.

This research helps identify factors that may contribute to engraftment syndrome, particularly in patients who receive daratumumab before ASCT. Understanding these risks could help doctors refine treatment plans and improve patient safety during stem cell transplants.

 

 

"Can we develop effective direct or indirect inhibitors of transcription factors? On the clinical evolution of protein degraders for multiple myeloma therapy"

Source

Meli R, Aksoy O, Vallet S, Slade D, Podar K. Can we develop effective direct or indirect inhibitors of transcription factors? On the clinical evolution of protein degraders for multiple myeloma therapy. Expert Opin Ther Targets. 2025 Mar 23. doi: 10.1080/14728222.2025.2482557. Epub ahead of print.  March 23, 2025. 

Overview

Transcription factors (TFs) are key proteins that control cell functions by responding to signals from inside and outside the cell. When these proteins are dysregulated, they can drive multiple myeloma (MM) progression, leading to uncontrolled growth, drug resistance, and immune evasion.

A major breakthrough in MM treatment came with the discovery that IMiDs (immunomodulatory drugs) work as molecular glue degraders. They reprogram an enzyme called cereblon (CRBN) to break down two critical transcription factors, IKZF1 and IKZF3, which were previously considered untreatable. This has led to new interest in targeted protein degradation (TPD) as a powerful cancer therapy. New drugs, such as CELMoDs (next-generation IMiDs), PROTACs (proteolysis-targeting chimeras), and degronomids, are being developed to improve MM treatment by breaking down harmful proteins more effectively.

CELMoDs are already changing the treatment landscape for MM, and early research on PROTACs looks promising. However, scientists still need a deeper understanding of TF biology and better drug-screening tools to unlock the full potential of targeted protein degradation in multiple myeloma.

 

 

"CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy"

Source

Bert Luyckx, Maaike Van Trimpont, Fien Declerck, Eleni Staessens, Annick Verhee, Sara T’Sas, Sven Eyckerman, Fritz Offner, Pieter Van Vlierberghe, Steven Goossens, Dorien Clarisse, Karolien De Bosscher, CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy, Pharmacological Research, 2025,107709, ISSN 1043-6618, https://doi.org/10.1016/j.phrs.2025.107709. March 23, 2025. 

Overview

Glucocorticoids (GCs), like dexamethasone, are key drugs in treating multiple myeloma (MM), but some myeloma cells develop resistance, making treatment less effective. Researchers have discovered that a protein called CCR1, along with its partner CCL3, helps MM cells survive GC treatment.

Blocking CCR1 with a drug called BX471 made MM cells more sensitive to dexamethasone. This effect was seen in cell cultures, patient samples, and a mouse model of myeloma. The combination treatment increased cell death by shifting the balance of survival and death-related proteins and disrupting lysosomal function.

The study also found that glucocorticoids normally reduce CCR1 levels, but in resistant MM cells, this effect is weakened. Blocking CCR1 partially reversed resistance, suggesting that targeting CCR1 could be a new way to resensitize MM cells to glucocorticoid therapy and improve treatment outcomes.

 

 

"Magnetic resonance imaging–based nomograms predict high-risk cytogenetic abnormalities in multiple myeloma: a two-centre study"

Source

S. Liu, C. Liu, H. Pan, S. Li, P. Teng, Z. Li, J. Sun, T. Ren, G. Liu, J. Zhou, Magnetic resonance imaging–based nomograms predict high-risk cytogenetic abnormalities in multiple myeloma: a two-centre study, Clinical Radiology, Volume 82, 2025, 106768, ISSN 0009-9260, https://doi.org/10.1016/j.crad.2024.106768. March 2025. 

Overview

Researchers are exploring how MRI radiomics—advanced imaging analysis—can help predict high-risk cytogenetic abnormalities (HRCAs) in multiple myeloma (MM). Identifying these genetic changes early could improve treatment decisions and patient outcomes.

The study analyzed 195 MM patients from two medical centers who had MRI scans. Researchers developed prediction models using MRI features and patient data, testing them on separate patient groups. The models were evaluated for accuracy, sensitivity, and predictive power, with results showing that combining MRI data with age improved the ability to detect high-risk genetic changes.

The findings suggest that MRI radiomics could become a valuable tool for identifying high-risk MM patients before treatment begins. This approach may help doctors personalize therapies and improve prognosis evaluation.

 

 

"Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma"

Source

Yan, W., Shi, X., Zhao, Y. et al. Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma. Nat Commun 16, 2863 (2025). https://doi.org/10.1038/s41467-025-57966-5  March 24, 2025. 

Overview

The gut microbiome plays a key role in cancer by influencing the tumor microenvironment (TME) and altering blood metabolites. However, its impact on multiple myeloma (MM) remains unclear. This study found that MM patients have high levels of Lachnospiraceae bacteria and low levels of phosphatidylcholine (PC), a key blood metabolite.

Researchers discovered that Lachnospiraceae bacteria reduce PC levels in MM cells, which in turn strengthens the immune system's CD8 T cells. PC normally helps MM cells produce a protein called Sb9, which is released in exosomes and weakens CD8 T cells by interfering with p53, a tumor-suppressing protein. When PC levels drop, Sb9 production decreases, allowing CD8 T cells to remain active and fight MM cells more effectively.

These findings suggest that targeting Lachnospiraceae and PC could be a new strategy for treating MM. By understanding how gut bacteria and blood metabolites influence the immune system, researchers may develop new therapies to improve MM treatment.

 

 

"Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease ResultsDaratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results"

Source

Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hebraud, Cyrille Hulin, Marie-Christine Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jerome Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W.C.J. van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuilleme, Pieter Sonneveld; Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results. Blood 2025; blood.2024027620. doi: https://doi.org/10.1182/blood.2024027620  March 24, 2025. 

Overview

A long-term follow-up of the CASSIOPEIA trial confirms that adding daratumumab to standard multiple myeloma (MM) treatment improves outcomes for transplant-eligible newly diagnosed patients. The study tracked patients for over 80 months, evaluating minimal residual disease (MRD) negativity and progression-free survival (PFS).

Patients who received daratumumab with bortezomib, thalidomide, and dexamethasone (D-VTd) had higher MRD negativity rates after both induction (34.6% vs. 23.1%) and consolidation therapy (63.7% vs. 43.7%) compared to those receiving VTd alone. Importantly, daratumumab maintenance therapy further improved MRD negativity and PFS, regardless of the patient’s initial risk level.

Overall, D-VTd followed by daratumumab maintenance led to the deepest and most sustained MRD negativity, translating to long-term PFS benefits. These findings reinforce daratumumab-based therapy as a powerful strategy for improving MM treatment outcomes.

 

 

"A longitudinal study of right ventricular function of patients with multiple myeloma treated with carfilzomib"

Source

Basin S, Cezar M, Fraix A, Pace N, Filippetti L, Schulmann S, Selton-Suty C, Huttin O, Chabot F, Chaouat A, Valentin S. A longitudinal study of right ventricular function of patients with multiple myeloma treated with carfilzomib. ERJ Open Res. 2025 Mar 24;11(2):00861-2024. doi: 10.1183/23120541.00861-2024.  March 24, 2025. 

Overview

A new study suggests that carfilzomib, a proteasome inhibitor used to treat multiple myeloma, may affect right ventricular (RV) heart function. Previous research has linked carfilzomib to cardiovascular side effects, including reduced left ventricular function and an increased risk of pulmonary arterial hypertension (PAH). However, its impact on RV function had not been well studied.

Researchers at Nancy University Hospital in France followed 36 multiple myeloma patients who received carfilzomib. Each patient underwent an echocardiogram (TTE) before starting treatment and again after about 10 months. The results showed a significant decrease in a key RV function measurement called TAPSE, even though no major medical events occurred to explain the decline.

While left ventricular function remained stable, the drop in TAPSE suggests that carfilzomib may cause RV toxicity. The exact clinical impact is still unclear, but patients on carfilzomib may need closer heart monitoring, especially for RV function. The study highlights the importance of regular echocardiograms to track potential heart changes during treatment.

 

 

"Design and synthesis of a clickable cell-permeable pseudopeptide Pin1 inhibitor with antiproliferative effects on human multiple myeloma cell line"

Source

Meneghelli L, Davidson S, Gineste A, El Guermah L, Kellouche-Gaillard S, Carreiras F, Carlier L, Nadal S, Larregola M, Pytkowicz J, Zanato C. Design and synthesis of a clickable cell-permeable pseudopeptide Pin1 inhibitor with antiproliferative effects on human multiple myeloma cell line. Chem Commun (Camb). 2025 Mar 24. doi: 10.1039/d4cc05968a. Epub ahead of print.  March 24, 2025. 

Overview

Researchers have developed a new class of small molecules that can enter cells and bind to Pin1, a protein involved in cancer growth. These molecules, called pseudopeptide ligands, could be useful for drug development and biochemical research.

The team tested how well these compounds bind to Pin1 using NMR analysis. One standout compound, 4b, showed strong cell penetration, the ability to block Pin1 activity, and an antiproliferative effect—meaning it slowed the growth of multiple myeloma cells.

These findings suggest that 4b and similar compounds could be further explored as potential treatments for multiple myeloma.

 

 

"Carfilzomib in Relapsed/Refractory Multiple Myeloma Patients – Real World Evidence – Experiences of the Croatian Cooperative Group for Hematologic Diseases (KROHEM)"

Source

Davor Galusic, Josip Batinic, Ivan Krecak, Barbara Dreta, Delfa Radic Kristo, Mario Pirsic, Goran Rincic, Jasminka Sincic-Petricevic, Toni Valkovic, Milan Vujcic, Marin Simunic, Karla Misura Jakobac, Martina Sedinic Lacko, Klara Brcic, Vlatka Perisa, Fran Petricevic, Dragana Grohovac, Hrvoje Holik, Martina Moric Peric, Ivan Zekanovic, Petra Bernes, Luka Kuzat, Ilenia Romic, Dubravka Zupanic Krmek, Sandra Basic-Kinda, Carfilzomib in Relapsed/Refractory Multiple Myeloma Patients – Real World Evidence – Experiences of the Croatian Cooperative Group for Hematologic Diseases (KROHEM), Cancer Treatment and Research Communications, 2025, 100912, ISSN 2468-2942, https://doi.org/10.1016/j.ctarc.2025.100912. March 24, 2025

Overview

A new real-world study from Croatia confirms that carfilzomib-based treatments are effective for patients with relapsed or refractory multiple myeloma (RRMM). Researchers analyzed data from 119 patients across 14 medical centers, showing that 61.7% responded to treatment, with 18.7% achieving complete remission. Patients lived an average of 13.2 months, with disease progression occurring at around 9.4 months. Those receiving a three-drug combination (triplet therapy) had significantly better outcomes than those on carfilzomib with dexamethasone alone.

The study also highlighted common side effects, including anemia and low platelet counts, while 16% of patients experienced heart-related complications. Despite these risks, the results support the continued use of carfilzomib-based regimens, particularly in earlier treatment lines and as part of a triplet therapy. These findings provide valuable real-world evidence that aligns with clinical trial data, reinforcing carfilzomib’s role as an effective treatment option for RRMM.

 

 

"Health care systems as determinants of outcomes in multiple myeloma: final results from the Latin American MYLACRE study"

Source

Vania Hungria, Rafael Gaiolla, Kenny Galvez, Guillermina Remaggi, Natalia Schutz, Rosane Bittencourt, Angelo Maiolino, Guillermo Quintero-Vega, Maria Silvana Cugliari, Walter Moises Tobias Braga, Carolina Colaco Villarim, Edvan Crusoe, Alicia Ines Enrico, Gaston Caiero, Jandey Bigonha, Fernanda Lemos Moura, Jair Figueroa, Claudia Lucia Sossa Melo, Milton Lombana, Huiling Pei, Mariana Fernandez, Jaqueline Saes, Damila Cristina Trufelli; Health care systems as determinants of outcomes in multiple myeloma: final results from the Latin American MYLACRE study. Blood Adv 2025; 9 (6): 1293–1302. doi: https://doi.org/10.1182/bloodadvances.2024013838 March 25, 2025 

Overview

A new study highlights major disparities in multiple myeloma treatment across Latin America, particularly between public and private healthcare systems. Researchers analyzed 1,029 patients from Argentina, Brazil, Colombia, Mexico, and Panama, revealing that patients in private hospitals had better access to advanced treatments—such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies—and were more likely to be eligible for stem cell transplants.

These differences impacted survival outcomes. Patients in private institutions lived a median of 53.3 months, compared to 44.6 months in public hospitals. Although the gap was not statistically significant, the findings suggest that limited access to novel therapies in the public sector may affect long-term survival. The study underscores the need for healthcare improvements in public hospitals to ensure equitable treatment for multiple myeloma patients in Latin America.

 

 

"Targeting the HuR/E2F7 axis synergizes with bortezomib against multiple myeloma"

Source

Jia, My., Wu, C., Fu, Z. et al. Targeting the HuR/E2F7 axis synergizes with bortezomib against multiple myeloma. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01529-3  March 25, 2025.  

Overview

Relapse and drug resistance are major challenges with multiple myeloma (MM). A new study highlights human antigen R (HuR) as a potential therapeutic target for MM. Researchers found that HuR is highly expressed in MM patients and linked to poor prognosis. Blocking HuR—using either shRNA or the inhibitor CMLD-2—significantly slowed MM cell growth and improved drug response in both lab and animal models.

Further analysis revealed that HuR increases the stability of E2F7, a molecule associated with worse outcomes. Lowering E2F7 levels reduced MM cell growth, while higher levels counteracted the benefits of HuR inhibition. Notably, blocking HuR enhanced the effectiveness of bortezomib, a standard MM treatment. The combination of CMLD-2 and bortezomib worked together to fight MM, suggesting that targeting the HuR/E2F7 pathway could improve treatment outcomes.

A new study highlights major disparities in multiple myeloma treatment across Latin America, particularly between public and private healthcare systems. Researchers analyzed 1,029 patients from Argentina, Brazil, Colombia, Mexico, and Panama, revealing that patients in private hospitals had better access to advanced treatments—such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies—and were more likely to be eligible for stem cell transplants.

These differences impacted survival outcomes. Patients in private institutions lived a median of 53.3 months, compared to 44.6 months in public hospitals. Although the gap was not statistically significant, the findings suggest that limited access to novel therapies in the public sector may affect long-term survival. The study underscores the need for healthcare improvements in public hospitals to ensure equitable treatment for multiple myeloma patients in Latin America.

 

 

"Identification of a new micropeptide altKLF4 derived from KLF4 that influences myeloma chemotherapeutic sensitivity"

Source

Ruosi Yao, Yindi Zeng, Yaxin Zhang, Xu Cao, Jiwei Mao, Wenjing Li, Kailin Xu, Linlin Liu, Identification of a new micropeptide altKLF4 derived from KLF4 that influences myeloma chemotherapeutic sensitivity, Cellular Signalling, 2025,111767, ISSN 0898-6568, https://doi.org/10.1016/j.cellsig.2025.111767. March 25, 2025. 

Overview

One of the biggest challenges in multiple myeloma (MM) treatment is chemotherapy resistance. A new study has identified a novel micropeptide, altKLF4, that may play a role in this resistance. Researchers found that altKLF4 is highly expressed in newly diagnosed MM patients and that its presence reduces the effectiveness of proteasome inhibitors, a key class of MM drugs.

Further analysis showed that altKLF4 is linked to mitochondria, the energy centers of cells, and may affect a process called ferroptosis, a form of cell death that can help fight cancer. Experiments revealed that altKLF4 interacts with GPX4, a protein that helps cancer cells resist ferroptosis, making MM cells less sensitive to treatment. In mouse models, blocking GPX4 slowed tumor growth, but this effect was reversed when altKLF4 was present.

These findings suggest that altKLF4 could serve as a biomarker for drug-resistant MM and may help guide future treatments to overcome resistance.

 

 

"Prognostic impact of a senescence gene signature in multiple myeloma"

Source

Lehoczki, A., Menyhart, O., Andrikovics, H. et al. Prognostic impact of a senescence gene signature in multiple myeloma. GeroScience (2025). https://doi.org/10.1007/s11357-025-01622-9  March 25, 2025. 

Overview

Most cases of multiple myeloma (MM) occur in people over 60. Aging-related processes, like cellular senescence, are thought to play a key role in MM development. A new study analyzed gene expression data from 1,416 MM patients to see if genes linked to aging could predict survival.

Researchers used the SenMayo gene signature, a set of 122 aging-related genes, and found that higher expression of these genes was linked to longer survival. Patients with high SenMayo expression had a median survival of 57 months, compared to 36.1 months for those with lower expression. These findings were confirmed across multiple patient datasets, showing that the SenMayo signature is a strong, independent predictor of survival, even when considering other clinical factors.

This study highlights the importance of cellular aging in MM and suggests that aging-related genes could help predict patient outcomes. Future research may explore new treatments that target these aging pathways to improve survival in MM.

 

 

"Factors Influencing Fluorescence-Activated Cell Sorting for Multiple Myeloma Fluorescence in situ Hybridization: Real-World Experience"

Source

Choi J, Yu K, Lee ST, Shin S, Choi JR. Factors Influencing Fluorescence-Activated Cell Sorting for Multiple Myeloma Fluorescence in situ Hybridization: Real-World Experience. Ann Lab Med. 2025 Mar 25. doi: 10.3343/alm.2024.0582. Epub ahead of print.  March 25, 2025. 

Overview

Fluorescence in situ hybridization (FISH) is a key method for detecting genetic abnormalities in multiple myeloma, but it works best when plasma cells are enriched before testing. Researchers studied 457 bone marrow samples to understand what factors influence the success of fluorescence-activated cell sorting (FACS), a technique used for plasma cell enrichment, and to evaluate direct FISH as an alternative when FACS fails.

The study found that FACS was successful in 70.9% of cases, with a high detection rate of 94.8% for genetic abnormalities. Faster sample transfer improved FACS success, with a 77.1% success rate for transfers under two hours compared to 67.8% for longer transfers. The percentage of plasma cells in the sample was also crucial—successful cases had a median of 31.2% plasma cells, while failed cases had only 8.5%. However, when FACS failed, direct FISH still detected abnormalities in 43.6% of cases.

These findings suggest that optimizing sample handling and ensuring higher plasma cell counts can improve FACS success. While FACS-FISH is more sensitive, direct FISH remains a useful backup when plasma cell enrichment is insufficient.

 

 

"The Progress of Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Myeloma (Review)"

Source

Wang YN, Zhang CW, Gao YX, Ge XL. The Progress of Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Myeloma (Review). Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251321349. doi: 10.1177/15330338251321349. Epub 2025 Mar 25. 

Overview

One of the main treatments for multiple myeloma (MM) is autologous stem cell transplantation (ASCT), where the patient’s own stem cells are used to help treat the disease. Thanks to new medications, the treatment for MM patients who qualify for ASCT has improved, leading to a longer survival time, which has increased by 8-10 years.

The treatment process for MM patients who are candidates for ASCT includes several steps: induction therapy (to reduce cancer), stem cell collection, the transplantation itself, and then consolidation and maintenance therapy to help prevent the cancer from coming back. Even with new drugs, the goal is to control the disease over the long term. Early ASCT continues to show better progression-free survival (PFS), especially in younger patients who are newly diagnosed with MM. Additionally, patients with high-risk genetic factors may benefit from tandem transplantation (two stem cell transplants). This review highlights the role of ASCT in MM, patient eligibility, chemotherapy before transplant, the transplant process, and the use of maintenance therapy and salvage transplants after the procedure.

 

 

"Progress of immune senescence in multiple myeloma treatment resistance"

Source

Jia, Y., Yan, L., Fan, C. et al. Progress of immune senescence in multiple myeloma treatment resistance. Discov Onc 16, 402 (2025). https://doi.org/10.1007/s12672-025-02136-8  March 26, 2025. 

Overview

One of the major challenges in treating multiple myeloma (MM) is drug resistance. Recent research has shown that the immune system plays a key role in the development of MM, with immune senescence—where the immune system weakens due to aging or disease—being significant in MM treatment resistance. This paper explores how immune senescence is linked to MM development and how it may contribute to the resistance of MM treatments. Understanding this connection could lead to new research on overcoming drug resistance and finding better immunotherapy treatments for MM patients.

 

 

"Chemotherapy-Mediated Induction of PD-L1 via SEI1 Facilitates Myeloma Immune Evasion"

Source

R. Chen, Z. Li, Z. Fang, Z. Li, D. Yang, Y. Li, S. Liu, Z. Liu, R. Liu, H. Liu, Chemotherapy-Mediated Induction of PD-L1 via SEI1 Facilitates Myeloma Immune Evasion. Adv. Sci. 2025, 2411082. https://doi.org/10.1002/advs.202411082  March 26, 2025. 

Overview

While chemotherapy is still the main treatment for multiple myeloma (MM), immune checkpoint blockade immunotherapy has shown promise. Yet, it's unclear how chemotherapy affects immune checkpoint expression and immunotherapy effectiveness. This study discovered that chemotherapy drugs cause DNA damage, which activates a signaling pathway called cGAS/STING. This pathway increases the production of a protein called SEI1, which helps boost the expression of PD-L1, a molecule that allows myeloma cells to evade the immune system. Both lab and animal studies showed that using PD-L1 antibodies after chemotherapy enhances the ability of T cells to kill myeloma cells, making the treatment more effective. This research highlights a key mechanism for PD-L1 upregulation and suggests that combining chemotherapy with immunotherapy could improve treatment for MM.

 

 

"Effect of Bortezomib Treatment in Multiple Myeloma on Blood Coagulation Function, Renal Function, Immune Function, and the NF-κB Pathway-Associated Indicators."

Source

Tao J, Wang L, Gu Z, Zhang L. Effect of Bortezomib Treatment in Multiple Myeloma on Blood Coagulation Function, Renal Function, Immune Function, and the NF-κB Pathway-Associated Indicators. Br J Hosp Med (Lond). 2025 Mar 26;86(3):1-15. doi: 10.12968/hmed.2024.0701.  March 26, 2025. 

Overview

Velcade® (bortezomib), a drug used for both newly diagnosed and refractory myeloma, has shown promise, but its full impact on multiple myeloma (MM) is not well understood. This study aimed to explore how bortezomib affects coagulation, kidney function, immune function, and the NF-κB pathway in MM patients.

The study analyzed 120 MM patients who were treated at the First People’s Hospital of Nantong, China, between 2018 and 2023. Patients were divided into two groups: one received a standard treatment regimen (thalidomide, cyclophosphamide, and dexamethasone), while the other received the same treatment with the addition of bortezomib. The results showed that the group receiving bortezomib had significantly better outcomes, including higher hemoglobin levels, lower M protein levels, and improved coagulation and kidney function. Additionally, bortezomib helped reduce inflammation and immune suppression, contributing to longer progression-free survival (PFS) and reduced NF-κB activation.

The study suggests bortezomib improves the overall health of MM patients by enhancing coagulation, kidney function, and immune response, while also extending survival and inhibiting a key cancer-related pathway.

 

 

"Mechanisms of resistance to CAR-T cell therapy in multiple myeloma: latest updates from the 2024 ASH annual meeting"

Source

Hu, Y., Hou, J., Jiang, Z. et al. Mechanisms of resistance to CAR-T cell therapy in multiple myeloma: latest updates from the 2024 ASH annual meeting. Exp Hematol Oncol 14, 45 (2025). https://doi.org/10.1186/s40164-025-00643-6  March 26, 2025. 

Overview

CAR T-cell therapy is a promising treatment for multiple myeloma (MM), but some patients develop resistance, making the treatment less effective over time. This resistance can happen due to factors like antigen escape (where cancer cells stop expressing the target protein), immune system suppression, and CAR T-cell exhaustion (when the engineered T cells lose their ability to fight cancer).

This study reviews the latest research from the 66th ASH Annual Meeting, exploring these resistance mechanisms and potential strategies to improve CAR T-cell therapy. Understanding these challenges could lead to better treatments and longer-lasting benefits for MM patients.

 

 

 

"Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword"

Source

Kamrani, S., Naseramini, R., Khani, P. et al. Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword. Cancer Cell Int 25, 117 (2025). https://doi.org/10.1186/s12935-025-03741-x  March 26, 2025. 

Overview

While multiple myeloma (MM) damages bones, it is not classified as a primary bone cancer. The bone marrow environment plays a key role in how MM grows and responds to treatment.

This review focuses on mesenchymal stromal cells (MSCs), which interact with myeloma cells and other bone marrow components. MSCs influence MM by promoting inflammation, altering tumor genetics, affecting immune checkpoint inhibitors, and contributing to drug resistance. Understanding how MSCs support MM progression could help researchers develop better treatments.

 

 

"Exosome-transmitted HSPA9 facilitates bortezomib resistance by targeting TRIP13/USP1 signaling in multiple myeloma"

Source

Shi, M., Shen, N., Liu, X. et al. Exosome-transmitted HSPA9 facilitates bortezomib resistance by targeting TRIP13/USP1 signaling in multiple myeloma. Cell Commun Signal 23, 152 (2025). https://doi.org/10.1186/s12964-025-02158-3  March 26, 2025. 

Overview

Velcade®  (bortezomib, or BTZ) is an important drug for treating multiple myeloma (MM), but some myeloma cells develop resistance, making the treatment less effective. This study reveals how drug-resistant myeloma cells spread resistance to other cells through small particles called exosomes. These exosomes contain a protein called HSPA9, which helps protect another protein, TRIP13, from being broken down. TRIP13 plays a key role in drug resistance, allowing myeloma cells to survive BTZ treatment.

Researchers found that when HSPA9 was blocked in lab experiments and animal models, tumors shrank, and myeloma cells became more sensitive to BTZ. This discovery highlights a new way myeloma cells resist treatment and suggests that targeting HSPA9 could improve BTZ effectiveness. By disrupting this resistance mechanism, researchers may be able to develop new therapies that enhance treatment outcomes for patients with MM.

 

 

"Deep immune cell profiling in blood and bone marrow of early stage monoclonal gammopathy: an iStopMM and ECRIN-M3 collaborative study"

Source

Pérez-Escurza, O., Flores-Montero, J., Óskarsson, J.Þ. et al. Deep immune cell profiling in blood and bone marrow of early stage monoclonal gammopathy: an iStopMM and ECRIN-M3 collaborative study. Blood Cancer J. 15, 46 (2025). https://doi.org/10.1038/s41408-025-01255-3  March 27, 2025. 

Overview

Researchers are learning more about how the immune system plays a role in the development of monoclonal gammopathies (MG), including multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM). This study used advanced flow cytometry to analyze immune cells in the blood and bone marrow of people with early-stage MG conditions, such as MGUS, smoldering multiple myeloma (SMM), and smoldering Waldenström’s macroglobulinemia (SWM). The findings suggest that immune system changes occur even in the earliest stages of disease, possibly affecting how the body responds to abnormal plasma cells.

The study found shifts in immune cell populations, including lower neutrophil production in the bone marrow, increased monocyte activity, and changes in dendritic cells, which may influence how the immune system interacts with tumor cells. T-cell counts, particularly regulatory T-cells, were also altered, potentially leading to a weakened immune response. Natural killer (NK) cells, which help fight cancer, were reduced in the blood but increased in the bone marrow, suggesting they are being drawn into the tumor environment. B-cells, which produce antibodies, showed the most significant changes, with lower numbers of memory B-cells and plasma cells, which could impair the body's ability to fight infections and respond to new threats.

These findings suggest that immune system disruptions begin early in MG and evolve as the disease progresses. Understanding these immune changes may help identify new treatment strategies to slow or prevent disease progression.

 

 

"Belantamab Mafodotin Plus Proteasome Inhibition Efficacy Versus Comparators in Early Relapsed Myeloma: A Systematic Review and Network Meta-Analysis"

Source

Richter, J., Nooka, A., Rodríguez-Otero, P., Schjesvold, F., Katodritou, E., Combe, E., Scott, M., Cooper, L., Sly, I., Ballew, N., Bitetti, J., Boytsov, N., Purser, M. and McNamara, S. (2025), Belantamab Mafodotin Plus Proteasome Inhibition Efficacy Versus Comparators in Early Relapsed Myeloma: A Systematic Review and Network Meta-Analysis. Am J Hematol. https://doi.org/10.1002/ajh.27661  March 27, 2025.. 

Overview

A  phase III study, DREAMM-7, found that Blenrep (belantamab mafodotin) combined with bortezomib and dexamethasone (BVd) helped patients with relapsed or refractory multiple myeloma (RRMM) live longer without their disease worsening compared to daratumumab with bortezomib and dexamethasone (DVd).

To see how BVd compares to other treatments, researchers reviewed data from 12 studies, each testing different drug combinations that included a proteasome inhibitor (bortezomib or carfilzomib) plus dexamethasone. A network analysis linked these studies, allowing indirect comparisons.

Results showed that BVd provided better progression-free survival (PFS) than all other regimens, including those with daratumumab or isatuximab plus carfilzomib and dexamethasone. Overall survival also improved with BVd compared to other treatments. These findings suggest BVd may be a strong option for treating RRMM in earlier treatment stages.

 

 

"Outcomes of Patients With Extramedullary Disease in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma From the Pooled LocoMMotion and MoMMent Studies"

Source

Philippe Moreau, María-Victoria Mateos, Hartmut Goldschmidt, Maria Esther Gonzalez Garcia, Britta Besemer, Marta Sonia Gonzalez Perez, Mohamad Mohty, Joanne Lindsey-Hill, Suriya Kirkpatrick, Michel Delforge, Emanuele Angelucci, Francesco Di Raimondo, Ravi Vij, Margaret Doyle, Kathleen Gray, Claire Albrecht, Vadim Strulev, Imène Haddad, Silva Koskinen, Lorenzo Acciarri, Jozefien Buyze, Katja Weisel, Outcomes of Patients With Extramedullary Disease in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma From the Pooled LocoMMotion and MoMMent Studies, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.03.014. March 27, 2025. 

Overview

Patients with relapsed or treatment-resistant multiple myeloma (RRMM) who develop extramedullary disease (EMD) often have a poor prognosis, underscoring the need for better treatment options. Two studies, LocoMMotion and MoMMent-1, examined how RRMM treatments evolved between 2019 and 2022. Researchers analyzed data from these studies to compare treatment outcomes in patients with and without EMD. Of the 302 patients studied, 29 had EMD, but only 15 had confirmed extramedullary plasmacytomas (EMP), which are tumors located outside the bone marrow. These patients received 21 different treatment regimens, mostly chemotherapy-based.

Patients with EMD had poor responses to treatment. Only 24.1% responded, and their cancer progressed within a median of 2.66 months. The median survival time was just 7.16 months, and they typically needed a new treatment within 3.09 months. These results were worse than those seen in patients without EMD. Despite these challenges, 65.5% of EMD patients tried additional therapies, but few received newer treatments like bispecific antibodies or antibody-drug conjugates. None received CAR T-cell therapy.

These findings highlight the urgent need for more effective treatments for EMD and emphasize the importance of using clear definitions of EMD in clinical trials. Standardizing how EMD is classified and measured could help improve research and lead to better therapies for these high-risk patients.

 

 

"BCMA CAR-T therapy as salvage therapy in patients with plasmablastic myeloma"

Source

Jin, C., Deng, J., Jiang, Y., Zhu, J., Kang, L., & Li, S. (2025). BCMA CAR-T therapy as salvage therapy in patients with plasmablastic myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2481555  March 27, 2025. 

Overview

Plasmablastic myeloma (PBM) is a rare and aggressive form of multiple myeloma with a poor prognosis. Researchers studied the effectiveness and safety of CAR-T cell therapy targeting BCMA in six PBM patients treated in 2023. Some patients received single-target BCMA CAR-T therapy, while others received a dual-target approach (BCMA/CD19). A few also underwent stem cell transplantation before treatment. The patients had a median age of 55.5 years, and most had high-risk genetic features.

The results were encouraging, with 83.3% of patients responding to treatment. Four out of six patients achieved a complete response or better, and three reached the strictest definition of complete response. However, the disease remained difficult to control long-term. Two patients had at least six months of progression-free survival, but one died from a lung infection. The other four patients experienced disease progression and did not survive.

All patients experienced cytokine release syndrome (CRS), a common side effect of CAR-T therapy, though no deaths were related to CRS. Three patients had severe (grade 3–4) CRS, and two experienced mild neurotoxicity. Overall, the therapy was considered safe and effective as a last-resort treatment for PBM. Future studies will explore CAR-T therapy in combination with other treatments to improve long-term outcomes

 

 

"Modelling MRD changes in myeloma to understand treatment effects, predict outcomes, and investigate curative potential"

Source

Walter M. Gregory, Thomas J. Prior, J.Blake Bartlett, Pieter Sonneveld, Meletios A. Dimopoulos, Philippe Moreau, Saad Usmani, Thierry Facon; Modelling MRD changes in myeloma to understand treatment effects, predict outcomes, and investigate curative potential. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-3475  March 27, 2025. 

Overview

Researchers developed mathematical models to better understand how minimal residual disease (MRD) changes over time in multiple myeloma patients. By analyzing MRD data from three major clinical trials (MAIA, CASTOR, and POLLUX), they aimed to predict how long patients would stay in remission (progression-free survival or PFS) and to guide future treatment decisions, such as when to stop or change therapy.

The models revealed two key patterns: some patients with low MRD levels experienced rapid disease regrowth, while others maintained low MRD for a long time. Treatment was most effective at eliminating cancer cells within the first 6 to 12 months. Patients whose disease rebounded quickly from low MRD levels tended to have higher initial levels of residual cancer, even if they were considered MRD-negative. The model’s three-year predictions for PFS closely matched actual clinical trial results.

These findings suggest that mathematical modeling could provide early predictions of treatment outcomes, rather than waiting years for clinical trial data. Patients who show early signs of relapse might benefit from adding another treatment before their disease progresses. More research is needed to confirm these results across different studies and patient groups, but these models could help doctors design better treatment plans in the future.

 

 

"Carfilzomib prescribing patterns and outcomes for relapsed or refractory multiple myeloma: a real-world analysis"

Source

Dong, S., Banerjee, R., Khan, A.M. et al. Carfilzomib prescribing patterns and outcomes for relapsed or refractory multiple myeloma: a real-world analysis. Blood Cancer J. 15, 48 (2025). https://doi.org/10.1038/s41408-025-01256-2  March 28, 2025. 

Overview

Carfilzomib (K) is a common treatment for relapsed or refractory multiple myeloma (RRMM), but there is no clear agreement on the best dose or schedule. Researchers analyzed data from 486 U.S. patients to compare three different carfilzomib dosing patterns: 56 mg/m² once weekly (K56-1x), 56 mg/m² twice weekly (K56-2x), and 70 mg/m² once weekly (K70-1x). Over time, once-weekly dosing became more popular, with K70-1x use increasing from 21.1% in 2016 to 50.6% in 2023.

The study found no significant differences in progression-free survival (PFS) between the groups: K56-1x had a median PFS of 13.0 months, K56-2x had 13.2 months, and K70-1x had 10.9 months. Heart failure rates were low across all groups (<5%). These results suggest that twice-weekly carfilzomib does not improve outcomes in RRMM.

Among the three dosing strategies, K56-1x may offer the best balance of effectiveness, safety, and convenience, reducing the burden of frequent infusions. This information could help doctors make more patient-friendly treatment decisions.

 

 

"Brain-to-vein and vein-to-vein times and outcomes in CAR T-cell therapy in myeloma"

Source

Grischke, T.K., Cooperrider, J.H., Pula, A. et al. Brain-to-vein and vein-to-vein times and outcomes in CAR T-cell therapy in myeloma. Blood Cancer J. 15, 47 (2025). https://doi.org/10.1038/s41408-025-01262-4  March 28, 2025 

Overview

CAR T-cell therapy is a promising treatment for multiple myeloma, but delays in the approval and manufacturing process can affect patient outcomes. This study examined two key timeframes: brain-to-vein (B2V) time, which measures the delay from insurance approval request to T-cell collection, and vein-to-vein (V2V) time, which tracks the time from T-cell collection to infusion. Researchers explored how insurance type, disease characteristics, and other factors influenced these timelines and patient survival.

The study found that patients with Medicare had shorter B2V times and were more likely to have their T-cells collected within 15 days of approval. Nearly all early deaths—both before and after CAR T-cell therapy—occurred in patients with B2V times longer than 15 days, regardless of insurance type. However, the study did not find a significant link between insurance type, B2V, or V2V and overall survival. Other factors, such as younger age, higher disease burden, and prior BCMA-targeted therapy, were associated with worse progression-free and overall survival.

To improve access to CAR T-cell therapy, faster insurance approval and streamlined agreements with private insurers are needed. Healthcare providers should initiate the approval process as soon as a patient is eligible, and manufacturers should work to reduce production delays and offer more flexible scheduling for T-cell collection. Avoiding certain chemotherapy drugs before T-cell collection may also help ensure a smoother process. Expanding research across multiple centers and including a more diverse patient population will be important for confirming these findings and addressing potential disparities in access and outcomes.

 

 

"Pre-diagnostic serum immune marker levels and multiple myeloma: A prospective longitudinal study using samples from the Janus Serum Bank in Norway"

Source

Herdenberg S, Wibom C, Krop EJM, Langseth H, Vermeulen R, Harlid S, Wu WY, Späth F. Pre-diagnostic serum immune marker levels and multiple myeloma: A prospective longitudinal study using samples from the Janus Serum Bank in Norway. Cancer Prev Res (Phila). 2025 Mar 28. doi: 10.1158/1940-6207.CAPR-24-0501. Epub ahead of print.  March 28, 2025. 

Overview

Multiple myeloma (MM) develops from a precursor condition called monoclonal gammopathy of undetermined significance (MGUS), but it is difficult to predict which patients will progress to MM using routine clinical tests. Changes in certain blood markers related to the immune system might provide early clues about disease progression. However, previous studies have shown inconsistent results for some of these markers, including MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α.

This study examined blood samples from 293 patients who later developed MM and 293 cancer-free individuals. Some MM patients had samples collected up to 42 years before their diagnosis, allowing researchers to track changes over time. Three biomarkers—MIP-1α, VEGF, and TGF-α—were analyzed further because they were detected in most samples. The study found no clear link between these markers and MM risk when measured 20 years before diagnosis. However, levels of TGF-α significantly decreased as patients got closer to their MM diagnosis, suggesting it may be involved in the disease process.

While this study does not confirm a direct role for these biomarkers in predicting MM, it highlights the need for further research on how immune system changes over time might signal disease progression. Identifying better early warning signs could help improve monitoring and treatment strategies for MGUS patients at risk of developing MM.

 

 

"Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma"

Source

Guo, M., Meng, H., Sun, Y., Zhou, L., Hu, T., Yu, T., Bai, H., Zhang, Y., Gu, C. and Yang, Y. (2025), Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma. Basic Clin Pharmacol Toxicol, 136: e70027. https://doi.org/10.1111/bcpt.70027  March 28, 2025. 

Overview

Bruceine A (BA), a natural compound from the Brucea javanica plant, has shown anticancer properties, but its effects on multiple myeloma (MM) are not well understood.

This study found that USP13, a protein highly expressed in MM patients, is linked to worse outcomes and promotes MM cell growth. Researchers discovered that USP13 helps stabilize PARP1, a protein involved in DNA damage repair (DDR), allowing MM cells to survive and grow. By targeting USP13 and PARP1, BA can disrupt DDR, making it harder for cancer cells to repair themselves. Lab tests using MM cell lines, patient-derived tumors, and mouse models confirmed that BA effectively slowed MM progression.

These findings suggest that Bruceine A could be a promising new treatment for MM by blocking USP13/PARP1 signaling and interfering with the cancer cells' ability to repair DNA damage. More research is needed, but this natural compound could help pave the way for new therapeutic strategies in MM.

 

 

"YY1-induced transcription of AKR1C3 activates the Hedgehog signalling pathway to enhance lenalidomide resistance and glycolytic activity in multiple myeloma cells"

Source

Chen, Y., Zhang, A., Wang, Y. et al. YY1-induced transcription of AKR1C3 activates the Hedgehog signalling pathway to enhance lenalidomide resistance and glycolytic activity in multiple myeloma cells. Clin Exp Med 25, 99 (2025). https://doi.org/10.1007/s10238-025-01619-w  March 29, 2025. 

Overview

Lenalidomide (LEN) is a key treatment for multiple myeloma (MM), but many patients eventually become resistant to the drug, making it less effective. This study explored how two proteins—AKR1C3 and YY1—contribute to LEN resistance and how targeting them could help improve treatment outcomes.

Researchers created LEN-resistant MM cell lines and found that AKR1C3 and YY1 were highly active in these cells. When they blocked AKR1C3, MM cells became more sensitive to LEN, grew more slowly, and showed more DNA damage, making it harder for them to survive. They also discovered that YY1 helps activate AKR1C3, further driving resistance. The Hedgehog signaling pathway, known for its role in cancer growth, was also involved in this process.

Interestingly, the study found that fluticasone, a common asthma medication, could reverse some of the resistance effects, suggesting a potential new way to improve LEN treatment.

These findings highlight YY1 and AKR1C3 as key players in drug resistance and suggest that targeting these proteins could make MM cells more responsive to LEN, offering hope for better treatment strategies.

 

 

"Clinicians’ Perspectives and Methodological Application of Fluorescence in Situ Hybridization (FISH) to Define Cytogenetic Risk in Multiple Myeloma: An Italian, Real-World, Survey-Based Report from the European Myeloma Network (EMN) Italy"

Source

Lorenzo Cani, Maria Teresa Petrucci, Katia Mancuso, Renato Zambello, Laura Paris, Sara Aquino, Flavia Lotti, Francesco Vassallo, Norbert Pescosta, Micol Quaresima, Patrizia Tosi, Iolanda Donatella Vincelli, Sonia Ronconi, Nicola Giuliani, Francesco Pisani, Mario Luppi, Rita Rizzi, Rita Mazza, Delia Rota-Scalabrini, Claudia Cellini, Silvia Mangiacavalli, Giuseppe Pietrantuono, Maria Luisa Pioltelli, Antonietta Pia Falcone, Elisabetta Antonioli, Angelo Belotti, Sonia Morè, Benedetto Bruno, Mario Boccadoro, Mattia D'Agostino, Clinicians’ Perspectives and Methodological Application of Fluorescence in Situ Hybridization (FISH) to Define Cytogenetic Risk in Multiple Myeloma: An Italian, Real-World, Survey-Based Report from the European Myeloma Network (EMN) Italy, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.03.011. March 29, 2025. 

Overview

Fluorescence in situ hybridization (FISH) is the standard test for detecting genetic changes in multiple myeloma (MM) that help predict patient outcomes. However, how FISH is applied in Italy varies across medical centers.

A 2023 survey of 70 MM treatment centers found that 71% of centers performed FISH locally, while smaller centers sent samples to outside labs. There were differences in testing methods, including how cells were purified and the thresholds used to detect abnormalities.

Most centers tested for key genetic markers linked to MM prognosis, such as del(17p), t(4;14), t(14;16), and 1q gains or amplifications. Nearly 94% used FISH results to determine a patient’s disease stage, while 69% used an updated staging system (R2-ISS).

While most centers tested all newly diagnosed patients, some skipped testing in older patients (over 80 years old). When MM relapsed, 53% of centers repeated FISH testing, while others only did so in specific cases.

This study highlights the need for standardized FISH testing guidelines in Italy to ensure all MM patients receive the most accurate prognosis and best possible treatment.

 

 

"Outcomes of patients with multiple myeloma undergoing autologous transplant with suboptimal pretransplant response"

Source

Pasvolsky O, Abid MB, Milton DR, Tanner MR, Bashir Q, Srour S, et al. Outcomes of patients with multiple myeloma undergoing autologous transplant with suboptimal pretransplant response. Br J Haematol. 2025; 00: 1–7. https://doi.org/10.1111/bjh.20062  March 30, 2025. 

Overview

This study focused on newly diagnosed multiple myeloma (NDMM) patients who underwent autologous hematopoietic cell transplantation (autoHCT) after not responding well enough to their initial treatment. Researchers looked at 1109 patients treated between 2005 and 2021, specifically those who had a response worse than very good partial response (<VGPR) before transplant.

The study found that the median progression-free survival (PFS) was about 39 months, and the median overall survival (OS) was about 104 months. However, patients with high-risk genetic factors had worse outcomes, with median PFS of about 25 months and median OS of 70 months.

Key findings showed that post-transplant maintenance treatment and achieving a complete response (CR) after the transplant were linked to better survival outcomes. Specifically, patients who achieved CR had significantly improved PFS and OS.

Overall, the study suggests that autoHCT for patients with less than optimal response to initial treatment still provides good long-term survival, with median PFS over 3 years and median OS over 8 years. Post-transplant maintenance therapy is important for improving these outcomes.

 

 

"Senescence profiling of monoclonal gammopathies reveals paracrine senescence as a crucial defense against disease progression"

Source

Borges, G.A., Diaz-delCastillo, M., Guilatco, A.J. et al. Senescence profiling of monoclonal gammopathies reveals paracrine senescence as a crucial defense against disease progression. Leukemia (2025). https://doi.org/10.1038/s41375-025-02572-z March 31, 2025. 

Overview

Multiple myeloma (MM) is a cancer of plasma cells that often develops from earlier conditions called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). While these early conditions have genetic similarities to MM, they do not cause organ damage, suggesting that plasma cells (PCs) in MGUS and SMM may enter a state of senescence—a type of growth arrest that stops cells from dividing.

This study found that senescent plasma cells were more common in MGUS patients compared to those with SMM or MM. In patients with stable (non-progressing) MGUS and SMM, researchers observed paracrine senescence—a process where senescent cells influence nearby cells in the bone marrow microenvironment to slow disease progression. These patients also showed specific senescence-associated secretory phenotype (SASP) signatures, which were linked to plasma cell burden and antibody levels.

However, in patients whose disease progressed from MGUS or SMM to MM, these senescence responses were missing. This suggests that the loss of senescence signals may be a key factor in disease progression.

These findings highlight the role of senescence in preventing MM and may open new pathways for targeting the bone marrow environment to delay or stop disease progression.

 

 

"Incidence of herpes zoster in transplant-ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone"

Source

Horigome, Y., Kamata, H., Michishita, Y. et al. Incidence of herpes zoster in transplant-ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-03980-8  March 31, 2025.  

Overview

The combination of daratumumab, lenalidomide, and dexamethasone (D-Rd) has significantly improved treatment outcomes for transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients. However, herpes zoster (shingles) and other infections can be serious complications, potentially interrupting treatment.

This study looked at 40 TIE-NDMM patients receiving D-Rd and found that 22.5% (9 patients) developed shingles, with cases occurring between 0.4 and 34.2 months after starting treatment (median: 10.7 months). The risk of shingles increased over time, reaching 13.3% at 12 months, 19.5% at 24 months, and 28.6% at 36 months. Researchers found no clear link between shingles and patient characteristics, disease features, or treatment response.

These findings highlight the high risk of shingles in TIE-NDMM patients on D-Rd, emphasizing the need for preventive antiviral medication. In Japan, antiviral prophylaxis is not yet covered by health insurance, but this study supports the case for future coverage.

 

 

"Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma"

Source

Tobias Tix, Mohammad Alhomoud, Roni Shouval, Gloria Iacoboni, Edward R. Scheffer Cliff, Doris K. Hansen, Saad Z. Usmani, Gilles Salles, Miguel-Angel Perales, David M. Cordas dos Santos, Kai Rejeski, Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma, Molecular Therapy,2025, ISSN 1525-0016, https://doi.org/10.1016/j.ymthe.2025.03.048. March 31, 2025. 

Overview

Bispecific antibodies (BsAb) are a promising treatment for B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), but they can cause serious immune-related side effects. This study analyzed data from 29 studies, including 2,535 patients, to assess non-relapse mortality (NRM)—deaths not caused by cancer progression. The overall NRM was 4.7%, with no significant difference between NHL (4.2%) and MM (6.2%). In NHL patients, real-world studies showed higher NRM than clinical trials, while in MM, higher response rates and longer follow-up were linked to increased NRM.

Infections were the leading cause of non-relapse deaths, accounting for 71.8% of cases, with nearly half attributed to COVID-19. A meta-regression comparing BsAb and CAR-T therapy found no significant difference in NRM. When COVID-19-related deaths were excluded, the overall NRM estimate dropped to 3.5%. These findings provide a benchmark for BsAb-related mortality and underscore the importance of infection prevention and monitoring in patients receiving this therapy

 

 

"Home-Based Daratumumab in Patients With Multiple Myeloma"

Source

Rosenberg, T., Kirkegaard, J., Gundesen, M.T., Rasmussen, M.K., Dieperink, K.B. and Lund, T. (2025), Home-Based Daratumumab in Patients With Multiple Myeloma. Eur J Haematol. https://doi.org/10.1111/ejh.14409   March 31, 2025. 

Overview

This study explored whether primary care nurses could safely administer subcutaneous daratumumab to multiple myeloma patients at home instead of in the hospital. Researchers followed 30 patients—18 who had already completed at least six treatment cycles and 12 who were newly starting. New patients received every second dose at home over six cycles, while ongoing patients had two out of three treatments at home over seven cycles.

Of the 123 planned hospital treatments, 122 (97.6%) were completed, while three were canceled. For the 144 planned home treatments, 133 (92.4%) were successful, six were redirected to the hospital, and five were canceled. There was no significant difference in the number of cancellations or redirections between hospital and home settings. Patients spent significantly less time on treatment at home, even when factoring in travel time, and reducing hospital visits did not lead to extra unplanned healthcare visits. These findings suggest that home-based administration of daratumumab is a safe, effective, and time-saving option for multiple myeloma patients.

 

 

"Hallmarks of terminal T-cell exhaustion are absent in multiple myeloma from diagnosis through maintenance therapy"

Source

Carolyn Shasha, David R Glass, Ernest Moelhman, Laura Islas, Yuan Tian, Tony Chour, Guoyue Xu, Gregory L. Szeto, Tao Peng, Xiaoling Song, Michelle Wurscher, Andrew J Cowan, Thomas F. Bumol, Troy R. Torgerson, Philip D Greenberg, Damian J Green, Evan W. Newell; Hallmarks of terminal T-cell exhaustion are absent in multiple myeloma from diagnosis through maintenance therapy. Blood 2025; blood.2024025655. doi: https://doi.org/10.1182/blood.2024025655  March 31, 2025. 

Overview

In multiple myeloma (MM), changes in the bone marrow environment can weaken the immune system’s ability to fight cancer. One way tumors suppress the immune response is by causing T cells—key immune defenders—to become "exhausted," a state where they lose their ability to attack cancer cells. While T cell exhaustion is well known in solid tumors, its role in MM remains unclear.

To better understand this, researchers analyzed CD8+ T cells from newly diagnosed MM (NDMM) patients using advanced single-cell sequencing and mass cytometry. Samples were taken from the bone marrow and blood at multiple stages of treatment, including diagnosis, induction therapy, stem cell transplant, and maintenance therapy. The study found a group of T cells with some exhaustion-like traits, but they lacked typical exhaustion markers and were not common in NDMM patients. Another group of T cells showed signs of activation, particularly in the blood, driven by cytokines rather than direct tumor interaction. Further testing revealed no evidence of fully exhausted, tumor-experienced T cells at any stage of the disease. These findings suggest that MM may use different immune evasion strategies than solid tumors, which could impact future treatment approaches.