A summary of some notable key multiple myeloma research from November-December 2025

Scope and Methodology

This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from November-December 2025. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, reviews, letters to the editor, correspondence, and the latest results of ongoing clinical trials, as well as the latest FDA news on myeloma drugs and treatments. It is intended for patients, care partners, and oncology professionals. This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on December 17, 2025. The blog reflects medical guidance available at the time of review and is not routinely updated.

At the end of each month, the International Myeloma Foundation (IMF) brings you some of the latest and most relevant news (myeloma research, clinical trials, treatments, drug authorizations, and more) to give a renewed sense of hope, courage, and resilience to the myeloma community.    

  
Guidelines and Recommendations

Sequencing BCMA- and GPRC5D-targeting immunotherapies in multiple myeloma: Practical guidance from the European Myeloma Network — Hemasphere (November 2025)

Background 
The treatment of multiple myeloma (MM), especially when the disease returns or stops responding to standard therapies, has changed rapidly. Several new immune-based treatments are now available. These include:

• CAR T-cell therapy 
• Bispecific antibodies (BsAbs) 
• Antibody-drug conjugates (ADCs)

These treatments target proteins in myeloma cells, mainly BCMA and GPRC5D.

Because there are now many options, deciding which treatment to use first – and how to sequence them – has become more complex. This guideline from the European Myeloma Network explains how to best use these therapies based on current evidence.

Key points

1. CAR T-cell therapy is preferred first (if possible)

• CAR T-cell therapy is usually the most effective treatment, offering high response rates, long remissions, and improved quality of life. 
• It is preferred before using BCMA-targeting bispecific antibodies or belantamab (belamaf), because these drugs may reduce how well later CAR T-cell therapy works. 
• Patients need good organ function and physical performance to qualify, and access may be limited.

2. When CAR T-cell therapy isn't possible.

Patients may receive:

• Belamaf-based combinations 
• Bispecific antibodies (off-the-shelf, no manufacturing wait)

These are helpful for patients who:

• Are not healthy enough for CAR T-cells 
• Need fast treatment because the disease is progressing quickly 
• Cannot access CAR T-cell therapy soon

Choice depends on side effects:

• Belamaf can cause eye problems 
• BCMA—bispecifics increase infection risk 
• GPRC5D—bispecifics can cause mouth and taste issues

3. Switching treatment targets often works best.

If one targeted therapy stops working, switching to a treatment that targets a different protein (BCMA → GPRC5D, or GPRC5D → BCMA) is usually more effective than using two therapies aimed at the same target.

4. If repeating the same target:

• Doctors should test the cancer again to make sure the target (like BCMA) is still present. 
• A treatment break (“drug-free interval”) of about 6–9 months between two BCMA-targeted therapies may improve outcomes. 
• A similar break may help when switching between bispecific antibodies.

5. Considering bispecific antibodies as “bridging therapy.”

If CAR T-cell treatment is planned but not immediately available:

• GPRC5D-directed bispecifics can be used temporarily (after cell collection) to control the disease. 
• BCMA-bispecifics should be avoided before CAR T, because they may reduce CAR T effectiveness.

Looking ahead 
Research is continuing to find the best order for these treatments, especially when used earlier in the disease. Future options may include:

• Dual-targeting treatments (e.g., therapies hitting BCMA and GPRC5D at the same time) 
• Trispecific antibodies (three targets) 
• New CAR T-cell therapies 
• Better testing to guide treatment decisions (e.g., identifying when the cancer has lost a target or when the immune system needs recovery)

These advances are expected to further improve survival and outcomes for patients with multiple myeloma.

Reference: 
van de Donk, N.W.C.J., Moreau, P., San-Miguel, J.F., Mateos, M.-V., Dimopoulos, M.A., Zweegman, S., Gay, F., Engelhardt, M., Mina, R., Zamagni, E., Delforge, M., Beksac, M., Spencer, A., Schjesvold, F., Driessen, C., Kaiser, M., Perrot, A., Wäsch, R., Korst, C.L.B.M., Broijl, A., Touzeau, C., Manier, S., Hajek, R., Bila, J., Seval, G.C., O'Dwyer, M., Ludwig, H., Fernandez de Larrea, C., Popat, R., Musto, P., Rodriguez-Otero, P., Yong, K., Kortüm, M., Rasche, L., Terpos, E., Raab, M.S., Boccadoro, M., Sonneveld, P., Einsele, H. and the EMN Guidelines Committee (2025), Sequencing BCMA- and GPRC5D-targeting immunotherapies in multiple myeloma: Practical guidance from the European Myeloma Network. HemaSphere, 9: e70260. https://doi.org/10.1002/hem3.70260

Optimizing the use of melflufen (melphalan flufenamide) in relapsed or refractory multiple myeloma: recommendations for clinical practice — Annals of Hematology (November 2025, Review)

What is melflufen? 
Melflufen is a newer type of chemotherapy medicine used to treat adults with relapsed or refractory multiple myeloma (RRMM)—a form of blood cancer that has come back or stopped responding to previous treatments. It’s given together with dexamethasone (a steroid).

Who can receive melflufen? 
It’s approved in the EU and UK for patients who:

• Have had at least three prior treatments, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. 
• Have disease progression after their last therapy. 
• If they had a previous stem cell transplant, at least three years should have passed since their last transplant.

How does it work? 
Melflufen is designed to enter cancer cells more easily than traditional chemotherapy. Once inside, it releases active substances that damage the DNA of the cancer cell, causing it to die. It can also work in cancer cells that have become resistant to other treatments.

How is it given? 
• Dose: 40 mg by intravenous (IV) infusion once every 28 days, with dexamethasone taken weekly. 
• For patients under 60 kg or with reduced kidney function, a lower dose (30 mg) is recommended. 
• It’s usually given through intravenously over 30 minutes and continued until the disease worsens or side effects become too strong.

Benefits seen in studies
• In studies with patients who had already tried many treatments, around 25–33% responded to melflufen. 
• Responses lasted an average of 4–6 months, and some patients stayed on treatment for more than a year. 
• It showed particular benefit in older patients, and those who had not recently received high-dose melphalan.

Common side effects
Most side effects are related to low blood counts. These include: 
• Low platelets (thrombocytopenia): may increase risk of bleeding. 
• Low white cells (neutropenia): may increase risk of infection. 
• Low red cells (anemia): can cause fatigue or weakness. 
• Infections: such as pneumonia, may occur in some patients. 
• Other mild effects can include nausea, diarrhea, and fatigue. Hair loss is rare, and nerve damage (neuropathy) is uncommon.

Managing side effects
• Blood counts should be checked regularly, especially during early cycles. 
• Transfusions or growth factors can be used to manage low blood counts. 
• Anti-nausea medications may be given before and after treatment. 
• Antibiotics may be needed for infections or in patients at high risk.

Who may benefit most
• Patients who have not recently received high-dose melphalan (or had a long response after it). 
• Older or frail patients unable to undergo intensive therapies like CAR-T cell therapy. 
• Patients with high-risk disease features (such as del(17p) or TP53 mutations). 
• Those with moderate kidney problems can also receive it with dose adjustments.

Who should avoid melflufen
• Patients with very poor bone marrow, liver, or kidney function (creatinine clearance <30 mL/min). 
• Patients progressing within 3 years after high-dose melphalan and stem cell transplant.

In summary
Melflufen plus dexamethasone is an effective treatment option for heavily pretreated or high-risk multiple myeloma patients, especially older adults or those unable to tolerate more aggressive therapies. It is generally well managed with standard precautions and regular monitoring.

Reference: 
Ludwig, H., Mai, E.K., Högner, M. et al. Optimizing the use of melflufen (melphalan flufenamide) in relapsed or refractory multiple myeloma: recommendations for clinical practice. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06659-6

Review

Optimizing oncology drug development: systematic review of 22 years of myeloma randomized controlled trials – Journal of the National Cancer Institute (November 2025)

What is the purpose of the study? 
This study looked at why some clinical trials for multiple myeloma (MM) succeed in meeting their main goals (endpoints) while others do not. Even though myeloma treatment has advanced greatly, some promising drugs fail in large trials after showing good early results.

How was the study conducted? 
Researchers reviewed 123 randomized controlled trials (RCTs) involving myeloma treatments published up to October 2023. They compared trial types and analyzed factors linked to success.

Key findings 
• Trials involving younger patients were more likely to meet their goals. 
• Trials that used progression-free survival as the main goal were more successful than those using overall survival. 
• Whether a trial compared two treatments directly (head-to-head) or tested adding a new drug to an existing treatment (add-on) did not affect the chance of success.

Why this study matters 
Trials in myeloma are more likely to succeed when they include younger participants and measure how long treatment controls the disease, rather than how long patients live overall. These findings can help researchers, doctors, and regulators design better trials and speed up progress in developing effective myeloma treatments.

Reference: 
Maria Mainou, Muatassem Alsadhan, Kalliopi Tsapa, Alissa Visram, Hira Mian, Rakesh Popat, Elias K Mai, Rajshekhar Chakraborty, Samer Al Hadidi, Meera Mohan, Aniko Szabo, Oliver Van Oekelen, Edward R Scheffer Cliff, Ghulam Rehman Mohyuddin, Optimizing oncology drug development: systematic review of 22 years of myeloma randomized controlled trials, JNCI: Journal of the National Cancer Institute, 2025;, djaf326, https://doi.org/10.1093/jnci/djaf326

CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization — Cell Communication and Signaling (November 2025)

Overview 
Natural killer (NK) cells are part of the body’s first line of defense against infections and cancers like multiple myeloma (MM). In MM, these NK cells often lose strength and number, especially in patients whose disease has returned or stopped responding to treatment.

New treatment approach 
Scientists are developing a new therapy that combines NK cells with chimeric antigen receptors (CARs) — special proteins that help NK cells better recognize and destroy myeloma cells. These “CAR-NK” cells are being studied as a promising “off-the-shelf” treatment, meaning they could be prepared in advance and used for many patients without needing to be customized each time.

Research findings 
• In laboratory and animal studies, CAR-NK cells strongly attacked and killed myeloma cells. 
• Newer designs, like dual CAR-NK cells, may prevent cancer cells from escaping immune attack. 
• Early human trials show CAR-NK therapy appears to be safe and well tolerated, though more studies are needed to confirm how effective it is.

Ethical considerations 
Developing CAR-NK therapy requires strict attention to patient safety and ethics. Researchers must ensure: 
• Expert design and oversight of studies 
• Informed consent and privacy for participants 
• Careful monitoring of safety and long-term results 
• Fair access and cost control once the therapy reaches the market

Conclusion 
Multiple myeloma remains incurable, but CAR-NK therapy offers a hopeful new direction. By enhancing the body’s natural immune response, this approach could lead to safer, more effective treatments. Ongoing research will help determine the best ways to use CAR-NK therapy and understand its long-term benefits.

Reference: 
Yazdanparast, S., Bakhtiyaridovvombaygi, M., Davoodi-Moghaddam, Z. et al. CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization. Cell Commun Signal 23, 485 (2025). https://doi.org/10.1186/s12964-025-02443-1

Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials — Cureus (December 2025)

What is the purpose of this review? 
Relapsed or refractory multiple myeloma (RRMM) is hard to treat, especially when patients have already received many previous therapies. New drugs called BCMA-targeted bispecific antibodies (bsAbs) are being studied. These medicines help the immune system attack myeloma cells and may offer new hope for patients with advanced disease.

This review looked at all available clinical trials to understand how well these drugs work and how safe they are.

Key findings 
• Out of more than 2,200 papers, 11 clinical trials were identified, involving 910 patients who had received many previous treatments. 
• Seven bsAbs were studied, including teclistamab, elranatamab, ABBV-383, and ALNUC, among others. 
• Response rates were promising: 
       - Elranatamab: 61–64% of patients responded 
       - Teclistamab: 40–78% 
       - ALNUC: 51% 
       - ABBV-383: 57%

Even patients who had already received other BCMA-targeted treatments (such as CAR-T therapy or antibody-drug conjugates)responded: 
• Elranatamab: 54% 
• Teclistamab: 40%

Common side effects

• Cytokine release syndrome (CRS) – usually mild and manageable 
• Low blood counts (anemia, low white cells, low platelets) 
• Infections

Importantly: 
• No deaths from CRS were reported. 
• CRS was less common when drugs were given subcutaneously (injected under the skin). 
• Some patients needed dose adjustments or stopped treatment because of side effects, but this was uncommon.

How do bsAbs compare to other BCMA-targeted treatments? 
• CAR-T therapies and antibody-drug conjugates are effective but can cause more severe side effects and may not be available quickly. 
• Bispecific antibodies are “off-the-shelf,” meaning they can be given without having to create a personalized cell product. 
• Overall, bsAbs show strong activity with a manageable safety profile.

Limitations of current evidence 
• Most studies were early-phase trials with small groups of patients. 
• They did not include comparison groups, making it hard to measure how well these drugs perform against standard treatments. 
• Follow-up periods were short, so long-term safety is not yet known.

What this means for patients 
BCMA-targeted bispecific antibodies are a promising new treatment option for people with difficult-to-treat multiple myeloma. They have shown encouraging response rates—even in patients who have exhausted many other options—and side effects are generally controllable.

However: 
• More research is needed to know how long responses last. 
• Larger, longer-term studies will be required to understand which bispecific antibody works best, how to sequence treatments, and the long-term risks.

Conclusion 
BCMA-directed bispecific antibodies represent an important and growing treatment option for relapsed or refractory multiple myeloma. Early results are encouraging, but more robust clinical trials are needed to determine their long-term effectiveness and best use in patient care.

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

MRD contamination in peripheral blood autologous stem cell grafts: implications for relapse and prognosis in multiple myeloma — Leukemia & Lymphoma (December 2025)

Background 
Minimal residual disease (MRD) refers to the tiny number of myeloma cells that remain in the body after treatment. Detecting MRD has become one of the most important ways to understand how well a patient with multiple myeloma (MM) is responding to therapy and to estimate the risk of the disease returning.

• Patients who reach MRD negativity generally live longer and stay in remission longer. 
• Many large studies and clinical trials show that MRD negativity is one of the strongest predictors of good outcomes. 
• Because of this strong evidence, MRD is now being used more often to help guide treatment decisions.

Stem cell grafts and MRD 
Before an autologous stem cell transplant (ASCT), doctors collect a patient’s own stem cells from the blood. Sometimes these collections contain small numbers of clonal plasma cells (CPCs)—cancerous myeloma cells. Testing for MRD in these stem cell grafts helps estimate how much disease is left at the time of collection.

Key points
• Detecting MRD in the graft does NOT mean the graft itself will cause relapse. 
• Instead, it reflects a higher amount of remaining disease in the body at the time of collection. 
• Patients with MRD-positive grafts tend to have shorter remission and survival, making it a useful risk-stratification tool.

How MRD is measured 
Different technologies detect extremely small numbers of cancer cells: 
• Flow cytometry (standard or next-generation flow / NGF) 
• Next-generation sequencing (NGS) 
• PCR-based methods

NGS and NGF are the most sensitive, able to detect 1 myeloma cell among 100,000–1,000,000 normal cells.

Limitations of graft MRD testing 
• Graft MRD is tested only once, at the time of stem cell collection, so it cannot track changes over time. 
• It is best used alongside other clinical information, including bone marrow MRD and genetic risk.

Clinical implications 
For patients whose grafts test MRD-positive:

• It signals a higher-risk situation, but not an inevitable relapse. 
• Doctors may recommend: 
     - More intensive or tailored therapy before or after transplant 
     - Maintenance treatment with newer agents 
     - More frequent MRD monitoring in bone marrow or blood

• Removing myeloma cells from the graft (“graft purging”) is possible but has not consistently improved patient outcomes.

Stem cell mobilization 
Collecting stem cells usually requires medications like G-CSF, sometimes with chemotherapy or drugs such as plerixafor, to help release stem cells from the bone marrow. Different mobilization methods may impact stem cell yield and tumor contamination, but no single approach is yet proven ideal for every patient.

Relationship between graft MRD and bone marrow MRD 
Studies show a clear connection between MRD in the graft and MRD in the bone marrow. Because graft testing is less invasive and more consistent, it may become a useful supportive tool in monitoring disease burden.

Takeaways for patients 
• MRD is a powerful predictor of outcomes in multiple myeloma. 
• MRD detected in stem cell grafts does not directly cause relapse but reflects a higher level of remaining cancer at the time of transplant preparation. 
• Patients with MRD-positive grafts may benefit from closer monitoring and more individualized treatment plans. 
• Combining graft MRD with bone marrow MRD, genetic testing, and clinical features provides the clearest picture of patient risk and helps guide therapy.

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

Research

Evaluating the real-world value of daratumumab addition to multiple myeloma induction therapy by real-world minimal residual disease assessment and extended genetic profiling — Clinical Lymphoma Myeloma and Leukemia (November 2025)

Background 
For patients with newly diagnosed multiple myeloma (NDMM) who are eligible for a stem cell transplant, the combination of daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) has become the standard first treatment in Europe. Earlier studies, like the CASSIOPEIA trial, showed that adding daratumumab improves treatment responses and helps patients stay in remission longer compared with VTd alone.

What is the purpose of the study? 
Doctors at the Royal Marsden Hospital reviewed the outcomes of 173 patients treated with either Dara-VTd or VTd between 2021 and 2024. They looked at how well patients responded after stem cell transplant, including how many became minimal residual disease (MRD) negative — meaning no cancer cells could be detected with highly sensitive testing.

Key findings

• Overall response after transplant was better with Dara-VTd (97%) than VTd (87%). 
• Deep response (MRD negativity) was also higher with Dara-VTd (79%) than VTd (56%). 
• Patients with fewer high-risk genetic changes benefited most from Dara-VTd. 
• After 2 years, the percentage of patients who remained cancer-free (progression-free survival) was: 
     - Dara-VTd: 97% (no high-risk genes), 94% (1 high-risk), 64% (2 or more high-risk) 
     - VTd: 83%, 62%, and 56%, respectively. 
• Even though Dara-VTd was clearly better, patients with multiple high-risk genetic features still had worse outcomes, showing that more personalized treatment strategies are needed for this group.

Additional insights 
• Routine MRD testing after transplant can help doctors quickly assess how well new treatments work in real-world settings, without waiting many years for relapse data. 
• The study also showed that daratumumab did not prevent successful stem cell collection, an important step before transplant. 
• Comprehensive genetic testing was crucial for identifying patients at higher risk, and ongoing access to these advanced tests is important for personalized care.

Conclusion 
Adding daratumumab to standard VTd treatment improves the depth and quality of response for most transplant-eligible myeloma patients in real-world practice. However, those with multiple high-risk genetic abnormalities continue to have poorer outcomes and may need more intensive or tailored therapies. Continued MRD monitoring and genetic testing will be key to guiding future treatment decisions.

Reference: 
Giuseppe Bertuglia, Elisa Seneca, Timothy Corbett, James Croft, Pawel Kaczmarek, Lauren Ellis, Chin Neoh, Edward Renaudon-Smith, Lewis Vanhinsbergh, Jindriska Lindsay, Stefania Bonetto, Sigurdur Y Kristinsson, Dingle Spence, Guy Pratt, Graham Jackson, Mark Ethell, Emma Nicholson, Christina Messiou, Tommy Brown, Leonora Conneely, Tracy Thornton, Lynnsay Fuller, Mikel Valganon Petrizan, Alan Dunlop, Katy Smith, Francesca Gay, Charlotte Pawlyn, Kevin D Boyd, Martin F Kaiser, Evaluating the real-world value of daratumumab addition to multiple myeloma induction therapy by real-world minimal residual disease assessment and extended genetic profiling, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.11.003.

CD38-specific nanobody-based bispecific antibody recruiters (BARs) redirect complement-dependent cytotoxicity toward multiple myeloma cells — Scientific Reports (November 2025)

Background 
Researchers are developing a new type of treatment tool called bispecific antibody recruiters (BARs) that use nanobodies—very small antibody-like proteins—to help the immune system kill multiple myeloma (MM) cells. These BARs are designed to attach to CD38, a protein commonly found on myeloma cells, and then “recruit” the body’s own antibodies to destroy these cancer cells.

Key findings 
• BARs can effectively kill myeloma cells in lab tests. They worked both in cell lines and in patient samples. 
• Using two BARs together was much more powerful than using one alone. Targeting two different parts of CD38 helped the immune system activate complement (a natural cell-killing system) more effectively. 
• BARs did not harm red blood cells or cells protected by natural “shield” proteins, suggesting good safety potential. 
• Their activity depends on CD38 levels. Cells with higher CD38 were easier to kill. 
• Some BARs still work even when CD38 is blocked by daratumumab, a common MM drug—meaning they could be used alongside current treatments. 
• These BARs recruit many types of natural antibodies in the blood, not just a small subset, which could make them more effective than older technologies. 
• Their small size usually means they leave the body quickly, but binding to antibodies seems to help them stay in the bloodstream longer.

Advantages and future potential 
• BARs can be customized easily, allowing: 
    - Targeting two different locations on CD38  
    - Targeting two different tumor proteins at once (e.g., CD38 + BCMA), which may improve effectiveness and overcome treatment resistance.

• This approach builds on the success of nanobody-based CAR-T therapies already approved for multiple myeloma.

Conclusion 
These early laboratory results show that nanobody-based CD38 BARs can strongly and specifically kill myeloma cells, especially when two BARs are used together. They are promising candidates for future myeloma treatments, but animal studies and clinical trials are needed to determine their safety and effectiveness in patients.

Reference: 
Pape, L.J., Gebhardt, A.J., Dannenberg, M. et al. CD38-specific nanobody-based bispecific antibody recruiters (BARs) redirect complement-dependent cytotoxicity toward multiple myeloma cells. Sci Rep 15, 40376 (2025). https://doi.org/10.1038/s41598-025-25194-y

Functional and molecular analyses reveal impaired HSPCs in Multiple Myeloma patients post-induction — Stem Cells Translational Medicine (November 2025)

What is the purpose of the study? 
Autologous stem cell transplantation (ASCT) is a standard treatment for eligible people with multiple myeloma (MM). It works by giving high-dose chemotherapy and then returning the patient’s own blood stem cells to help the bone marrow recover.

However, some patients still relapse, and some experience slow or incomplete recovery of the immune system. This study looked closely at the quality and function of stem and progenitor cells collected from MM patients—both at diagnosis and after chemotherapy—to understand how to improve future transplants.

Key findings

1. Stem and progenitor cells from treated MM patients function poorly.

After chemotherapy, patients’ hematopoietic stem and progenitor cells (HSPCs) were less able to rebuild the blood and immune system, especially B cells, compared with cells from healthy donors or newly diagnosed patients.

2. Chemotherapy-treated patients’ CD34+ cells develop a “high-risk” myeloma-like gene signature.

Even though MM is a cancer of plasma cells, the researchers found that myeloid progenitors—cells that normally become granulocytes, monocytes, or platelets—showed gene activity similar to high-risk myeloma cells after treatment. These changes were not seen in true stem cells (HSCs), which kept a normal gene profile.

3. Problematic cells are mainly in specific progenitor groups.

The “abnormal” MM-like signature was found mostly in:

• Granulocyte–macrophage progenitors (GMPs) 
• Megakaryocyte–erythroid progenitors (MEPs) 
• Monocytes

These cell types appear to pick up disease-related traits, possibly influenced by MM cells or chemotherapy.

4. Removing these abnormal progenitors may improve transplant outcomes.

Because these altered cells may carry disease-linked programs back into the patient during ASCT, the study suggests that purifying the transplant product to enrich for true stem cells (HSCs) and remove GMPs/MEPs/monocytes could reduce relapse risk and improve recovery.

Why are these results important? 
• The findings challenge the assumption that only plasma cells are abnormal in MM. 
• They point to a broader impact of MM and chemotherapy on the blood-forming system, including early precursor cells. 
• Improving transplant purity—by removing progenitors with MM-like features—may help prevent relapse and improve immune recovery. 
• The study provides a potential explanation for why some patients experience poor recovery or early relapse after ASCT.

Limitations 
• The number of patient samples was small. 
• More research is needed to confirm that removing certain progenitors truly improves clinical outcomes. 
• Some hypotheses—such as myeloma cells influencing myeloid progenitors—require further experimental proof.

In summary 
Stem and progenitor cells collected after chemotherapy in MM patients may already show disease-related genetic changes and reduced ability to rebuild the immune system. Focusing on purer stem cell collections (with fewer altered myeloid progenitors) could potentially make autologous transplants safer and more effective.

Reference: 
Thanh Mai Baumhardt, Amanda Amoah, Markus Hoenicka, Andreas Liebold, Vadim Sakk, Karin Soller, Angelika Vollmer, Miriam Kull, Jan Kronke, Jan-Philipp Mallm, Hartmut Geiger, Medhanie Mulaw, Functional and molecular analyses reveal impaired HSPCs in Multiple Myeloma patients post-induction, Stem Cells Translational Medicine, Volume 14, Issue 11, November 2025, szaf061, https://doi.org/10.1093/stcltm/szaf061

Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics — Communications Biology (November 2025)

What is the purpose of the study? 
Multiple myeloma grows in the bone marrow — a very organized tissue where the location of each cell matters. This study used a new technology called spatial transcriptomics to look at gene activity directly within bone marrow tissue, keeping track of where different cells are located. The research included healthy mice, mouse models of myeloma, and bone marrow samples from myeloma patients.

How was the study conducted? 
• They used the 10X Visium Spatial Gene Expression platform to study bone marrow from preserved (FFPE) samples. 
• Because bone tissue is hard and must be decalcified (a process that can damage RNA), the team developed special methods to keep the samples usable. 
• They combined spatial data with single-cell RNA sequencing to identify which cells were present and how they interacted in the bone marrow.

Key findings

1. Myeloma cells (MM plasma cells) form distinct “spatial zones.”

The team identified: 
• Hotspots: areas rich in MM cells 
• Border zones: surrounding areas 
• Remote zones: farther away from the tumor

These zones showed different patterns of immune cell behavior and gene activity.

2. Myeloma cells are not all the same, even within the same tumor. 

Different groups of cancer cells showed different gene programs, which may help explain why patients with similar tumor sizes can have very different disease outcomes.

3. Immune cells change depending on their distance from the cancer. 
• More active T cells were found near MM hotspots. 
• More exhausted T cells (weaker, worn-out immune cells) were found farther away. This pattern resembles what is seen in solid tumors.

4. Certain disease-related pathways change across the bone marrow.

Pathways involving IL-17 signaling, NETosis (a process linked to inflammation and neutrophils), and osteoclast activity were different depending on how close the region was to the tumor. These patterns were seen in both mouse models and human bone marrow samples.

The technique works in human FFPE bone marrow biopsies. Despite technical challenges, the findings from mice were largely confirmed in MM patients with different levels of tumor burden.

Limitations 
• Only a small number of samples were studied. 
• The Visium technology does not provide true single-cell resolution. 
• Some cell types are too rare to analyze well. 
• Sample quality (affected by bone decalcification) may reduce accuracy. 
• Only one slide per sample was analyzed, which may miss variations in other parts of the bone marrow. 
• Current technology cannot measure patient-specific immune signatures like V(D)J sequences, which are important in myeloma biology.

Why this study matters 
This study shows it is possible to map out where myeloma cells and immune cells sit within the bone marrow and how they interact. Understanding this spatial “map” may help researchers discover:

• why the disease behaves differently from patient to patient, 
• how the tumor environment suppresses the immune system, and 
• new therapeutic targets based on the tumor’s surroundings.

Key takeaways 
The study demonstrates that spatial transcriptomics can successfully analyze bone marrow structure and identify important patterns in how myeloma develops and spreads. This approach may eventually support better diagnosis, disease monitoring, and treatment strategies.

Reference: 
Muiños-Lopez, E., Lopez-Perez, A.R., Sudupe, L. et al. Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics. Commun Biol 8, 1620 (2025). https://doi.org/10.1038/s42003-025-08975-z

Clinic-biological features and prognostic significance of MGUS-like myeloma who underwent to autologous stem cell transplantation – Clinical Lymphoma Myeloma and Leukemia (November 2025)

What is the purpose of this study? 
Multiple myeloma (MM) behaves differently from patient to patient. A newer model—the MGUS-like model—classifies MM patients into three groups based on the number and type of plasma cells in the bone marrow:

• MGUS-like 
• Intermediate 
• MM-like

These groups differ in how long patients stay in remission. This study looked at whether the MGUS-like classification can also help predict which patients benefit most from autologous stem cell transplantation (ASCT).

Key findings

1. MGUS-like patients have milder disease features.

Patients in the MGUS-like group had:

• lower disease stage (low ISS/R-ISS), 
• less anemia and kidney problems, 
• fewer cancerous plasma cells in the bone marrow, 
• lower levels of abnormal protein in the blood, 
• but more bone lesions and plasmacytomas (similar to “macro-focal myeloma”).

2. MGUS-like patients responded better to ASCT.

After transplant, 70% of MGUS-like patients reached: 
• complete response, and 
• minimal residual disease (MRD) negativity

This was significantly higher than: 
• 47% in the intermediate group
• 41% in the MM-like group

3. MGUS-like profile predicts longer remission.

The MGUS-like signature independently lowered the risk of relapse or death by 40–60% compared with the other groups—even though these patients often received less intensive post-transplant treatment.

What does this mean for patients?

• The MGUS-like profile can be measured before treatment using routine bone marrow tests. 
• It identifies a subgroup of MM patients with better responses to high-dose melphalan and ASCT. 
• Patients with an MGUS-like profile tend to have longer remission and better outcomes after transplant.

The MGUS-like classification helps pinpoint multiple myeloma patients who are most likely to benefit from autologous stem cell transplantation. These patients typically have milder disease but achieve deeper, longer-lasting remissions after transplant.

Reference: 
Borja Puertas, Elena Alejo, José J. Pérez-Morán, Fe Serra-Toral, Irene Padilla, Julio Dávila-Valls, Aránzazu García-Mateo, José María Alonso-Alonso, Roberto Hernández, Carlos Aguilar-Franco, Rosa López-López, Alfonso García-Coca, Alberto Cantalapiedra-Diez, Abelardo Bárez, Beatriz Rey-Búa, Lucía López-Corral, Juan Flores-Montero, M. Belén Vidriales-Vicente, Norma C. Gutiérrez, Verónica González-Calle, Fernando Escalante, Noemi Puig, Maria-Victoria Mateos, Clinic-biological features and prognostic significance of MGUS-like myeloma who underwent to autologous stem cell transplantation, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.11.007.

Lynozyfic (Linvoseltamab): A First-in-Class Off-the-Shelf T-Cell Redirector for Refractory Multiple Myeloma — eJHaem (November 2025, Letter to the Editor)

Summary 
On July 2, 2025, the U.S. FDA approved Lynozyfic (linvoseltamab-gcpt) for adults with relapsed or refractory multiple myeloma (RRMM) who have already received at least four treatments, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.

What makes Lynozyfic different? 
• It is the first approved bispecific antibody that targets BCMA on myeloma cells and CD3 on T cells. 
• It is given by IV infusion. 
• No lymphodepletion or personalized cell manufacturing is needed (unlike CAR-T therapy). 
• It is an “off-the-shelf” treatment that uses your own T cells immediately to kill cancer cells.

Current treatment landscape 
• Newly diagnosed patients often receive combination therapies (triplets or quadruplets), sometimes followed by stem-cell transplant. 
• Newer guidelines recommend quadruplet regimens with drugs like daratumumab to improve deep responses. 
• For relapse, options include CAR-T cell therapy and bispecific antibodies, but CAR-T can be limited by long manufacturing times and the need for chemotherapy before treatment. 
• Patients whose disease no longer responds to the main three drug classes (“triple-class refractory”) have very limited options.

How Lynozyfic works 
Lynozyfic is a bispecific T-cell engager that: 
• Grabs onto BCMA on myeloma cells. 
• Connects to CD3 on T cells. 
• Pulls them together so the T cells can directly kill the cancer cells.

This approach provides CAR-T–like activity without the delays and complications of manufacturing a personalized product.

Clinical results 
In a key phase I/II study:

• 64.5% of patients responded to treatment. 
• Nearly half had a very good partial response or better. 
• About 24% reached a complete response. 
• Responses were fast (about 1 month). 
• Responses lasted a median of ~29 months. 
• The drug worked well across different ages, races, and disease types.

Safety 
• Side effects were generally manageable. 
• Cytokine release syndrome (CRS) occurred in about half of patients but was mostly mild (Grade 1–2) and happened early in treatment. 
• Studies suggest lower rates of severe infections and neurologic side effects compared with some other bispecific antibodies.

Bottom line 
Lynozyfic offers a powerful, faster-to-access, off-the-shelf treatment for people with heavily pretreated or triple-class refractory myeloma. It combines strong effectiveness with a generally manageable safety profile and avoids the major logistical hurdles of CAR-T therapy.

Reference: 
Ur Rehman, R. (2025), Lynozyfic (Linvoseltamab): A First-in-Class Off-the-Shelf T-Cell Redirector for Refractory Multiple Myeloma. eJHaem, 6: e70182. https://doi.org/10.1002/jha2.70182

Defining the proteome of bone marrow plasma in multiple myeloma and monoclonal gammopathy of undetermined significance – Blood Cancer Journal (November 2025, Correspondence)

Background 
Plasma cell disorders include precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). These diseases develop in the bone marrow (BM), a key part of the immune system. While previous research has studied cancerous plasma cells themselves, much less is known about the proteins in the bone marrow fluid, which reflect what is happening in the tumor’s surrounding environment.

What is the purpose of the study? 
In this study, researchers used a sensitive technology called Olink proteomics to measure hundreds of proteins in bone marrow samples from people with MGUS, MM, and healthy controls. Their goal was to find proteins that could help diagnose or track these conditions and possibly point to new treatment targets.

Key findings 
• Many proteins differed between healthy individuals, MGUS, and MM. The protein patterns clearly separated healthy samples from disease samples. 
• Several proteins increased as the number of cancerous plasma cells went up. These included: 
   - BCMA, TACI, FCRL5, and CD79B — proteins involved in B-cell signaling. 
   - BCMA is already a treatment target for MM. 
   - FCRL5 and CD79B may be useful for future targets.

• Proteins that help cancer cells interact with or evade the immune system—such as SLAMF7 (a current MM drug target), CD48, LY9, SDC1 (CD138), PD-L1, and complement C3—were higher in MM. 
   - Some of these proteins (e.g., C3) were elevated even in MGUS, suggesting they may help detect early disease. 
• Metabolic proteins, involved in cholesterol, fat, and sugar processing, were also increased in both MGUS and MM. This suggests that metabolic changes begin early in the disease process. 
• The study also identified less well-known proteins (e.g., TXNDC5, EPO, ST6GAL1, CNTN5) that may play a role in MM development and may become future biomarkers or treatment targets. 
• Using public single-cell data, the researchers confirmed that many of these proteins are mainly produced by plasma cells, supporting their relevance to the disease.

Why this study matters 
• The bone marrow environment contains many proteins that may help doctors detect plasma cell diseases earlier, distinguish MGUS from MM, or monitor disease progression, especially in cases where traditional blood markers are not reliable (such as non-secretory MM). 
• Some proteins identified may offer new treatment opportunities in the future.

Limitations 
• The study had a small sample size, and patient groups differed in age and clinical features. 
• Larger studies are needed to confirm these findings and test whether these proteins can reliably track disease over time.

Reference: 
Hsu, JS., Yadav, U., Garapati, K. et al. Defining the proteome of bone marrow plasma in multiple myeloma and monoclonal gammopathy of undetermined significance. Blood Cancer J. 15, 202 (2025). https://doi.org/10.1038/s41408-025-01417-3

Comprehensive Review on Outcomes from Phase 3 Clinical Trials of Drugs in Multiple Myeloma — Cancer Treatment and Research Communications (November 2025)

Background  
Multiple myeloma often comes back after treatment. Over the past several years, major advances have greatly improved survival and quality of life for many patients.

Key points 
• Adding monoclonal antibodies, such as daratumumab, to standard treatment has significantly improved outcomes for both newly diagnosed patients and those whose cancer has returned. 
• Combination treatments that mix different types of medicines—like proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs)—provide better response rates. A common example is the VRd regimen (bortezomib, lenalidomide, dexamethasone). 
• For patients who have relapsed many times or whose disease no longer responds to standard therapy, CAR-T cell treatments, especially those targeting BCMA (such as cilta-cel), can offer deep and long-lasting remissions. 
• Maintenance therapy, usually with lenalidomide, is often used after initial treatment to keep the cancer under control for as long as possible. 
• New drugs, new combinations, and newer immune therapies (including bispecific antibodies) continue to be actively studied to give patients more effective and safer options.

Future directions 
• Treatment is becoming increasingly personalized, taking into account a patient’s age, overall health, and specific genetic features of cancer. 
• Minimal residual disease (MRD is becoming an important tool for deciding how long to continue treatment. 
• Researchers are working to make advanced therapies, including CAR-T cells, more widely available and affordable. 
• “Off-the-shelf” immune therapies, such as allogeneic CAR-T cells and bispecific antibodies, may make treatment faster and easier to access. 
• As research progresses, the goal is to move closer to a functional cure, making multiple myeloma a long-term manageable condition rather than a life-threatening illness.

Reference:
Sandeep Singh, Vivek Uttam, Shafiul Haque, Hardeep Singh Tuli, Pallavi Mishra, Aklank Jain, Comprehensive Review on Outcomes from Phase 3 Clinical Trials of Drugs in Multiple Myeloma, Cancer Treatment and Research Communications, 2025, 101041, ISSN 2468-2942, https://doi.org/10.1016/j.ctarc.2025.101041.

A multicenter observational retrospective study of second-line treatment with daratumumab–bortezomib–dexamethasone (DaraVd) in multiple myeloma patients refractory to lenalidomide — Clinical and Experimental Medicine (November 2025)

Background 
Lenalidomide is commonly used as the first treatment for newly diagnosed multiple myeloma. However, many patients eventually become “lenalidomide-refractory,” meaning the disease no longer responds to the drug. Treating these patients at their first relapse can be difficult.

What is the purpose of the study? 
This study looked back at the real-life experience of 85 patients in Italy who were treated with the combination of daratumumab, bortezomib, and dexamethasone (DaraVd) as their second treatment after lenalidomide stopped working.

Key findings 
• Good response rates: 86% of patients responded to treatment, and 61% had a deep response (very good partial response or better). 
• Treatment duration: The median time before the cancer worsened again was 15 months, and the median overall survival was 47 months. 
• Best outcomes:Patients who achieved a strong response (VGPR or better) had significantly longer periods without disease progression.

Side effects
About 85% of patients had at least one moderate or severe side effect. The most common problems were:

• Low blood counts 
• Infections (including pneumonia) 
• Fatigue 
• Nerve damage/tingling from bortezomib

Many patients needed dose reductions, especially for bortezomib, but only three stopped treatment because of side effects.

How DaraVd fits into current treatment options 
• More patients are now refractory to lenalidomide after first-line therapy, making second-line choices more complicated. 
• Many modern options (like CAR-T cell therapy or bispecific antibodies) are not available everywhere or may not be suitable for older or frailer patients. 
• Compared with some other drug combinations, DaraVd: 
    - Has a manageable side effect profile 
    - Can be used safely in older patients 
    - Is less demanding in terms of hospital visits 
• Remains effective even when other options are not possible

Bottom line 
For patients whose myeloma stops responding to lenalidomide after initial treatment, DaraVd is a practical and effective second-line therapy, especially for:

• Older or frail patients 
• Patients who cannot receive more intensive treatments 
• Those without access to advanced immunotherapies

Although newer treatments are emerging, DaraVd continues to be an important and accessible option for many people facing their first relapse.

Reference: 
Rizzello, I., Sacchetti, I., Barbato, S. et al. A multicenter observational retrospective study of second-line treatment with daratumumab–bortezomib–dexamethasone (DaraVd) in multiple myeloma patients refractory to lenalidomide. Clin Exp Med 26, 43 (2026). https://doi.org/10.1007/s10238-025-01956-w

The impact of CD81 on immune cells and clinical prognosis in multiple myeloma — Annals of Hematology (November 2025)

Background  
Even with modern treatments, myeloma often comes back and can be difficult to cure. Researchers are trying to understand why some patients do worse than others and how the immune system and certain cell markers influence outcomes. 

What is the purpose of the study? 
This study focused on CD81, a protein found on the surface of many cells, including myeloma cells. Among 178 newly diagnosed MM patients:

• About 60% had CD81-positive myeloma cells. 
• Patients with CD81-positive disease had shorter overall survival, even though the time before the cancer worsened (progression-free survival) was not significantly different. 
• High CD81 levels were linked to: 
   - Lower numbers of CD8 T cells in the blood (these are key immune cells that help kill cancer cells) 
   - Higher numbers of M2 macrophages, a type of immune cell that tends to support tumor growth and weaken the immune response

Together, these patterns suggest that CD81-positive myeloma creates a more “immunosuppressive” environment—meaning the immune system is less able to fight the myeloma.

The study also found:

• High CD206 (an M2 macrophage marker) was linked to worse survival. 
• High CD68 (a general macrophage marker, more associated with beneficial M1 macrophages) was linked to better outcomes. 
• CD81 did not significantly correlate with standard inflammation markers (like CRP or IL-6).

What this means 
• CD81 may be an important prognostic marker in multiple myeloma. 
• Patients with higher CD81 expression may have: 
   - A weaker antitumor immune response (fewer CD8 T cells) 
   - A stronger pro-tumor immune environment (more M2 macrophages) 
• This may explain why these patients have shorter survival, especially after the disease relapses. 
• CD81 might eventually become a target for new treatments, but more research is needed to understand exactly how it affects immune cells.

Key takeaways 
CD81 appears to influence both the behavior of myeloma cells and the surrounding immune environment. Patients with CD81-positive myeloma may have poorer outcomes because their immune system is less able to fight the disease. Future research may help clarify whether targeting CD81 or related immune pathways can improve treatment for MM.

Reference: 
Zhao, Q., LV, M., Yan, Q. et al. The impact of CD81 on immune cells and clinical prognosis in multiple myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06712-4

Patients and healthcare professionals’ perspectives on the implementation of shared decision making in multiple myeloma: a multinational qualitative study — BMC Medical Informatics and Decision Making (November 2025) 
 

What is the purpose of the study? 
Shared decision making (SDM) means that patients and healthcare professionals make treatment decisions together. This study looked at how well SDM is used in the care of people with multiple myeloma (MM). Researchers interviewed patients, hematologists, and nurses in nine countries to understand how SDM currently works, what gets in the way, and how it can be improved.

Key findings 
• Patients want different levels of involvement. 
Some want to be very involved in choosing treatments, while others prefer to let their doctor decide. Most still want clear information, a chance to ask questions, and to have their opinions respected.

• Experiences vary widely. 
Many hematologists felt they were practicing SDM, but patients often felt their preferences and concerns were not asked about directly. Patients also said their preferred way of receiving information was almost never checked.

• Some important topics are not discussed enough. 
Options such as no treatment or palliative care were rarely talked about, even when relevant. Patients said they would appreciate honest conversations about these choices.

• Nurses and others play a key role. 
Hematology nurses, other team members, families, and patient organizations provide vital support—explaining information, exploring concerns, and helping patients make decisions.

Barriers to shared decision making 
• Doctors’ reluctance to involve patients or share difficult information 
• Patients feel overwhelmed or emotional 
• Limited easy-to-understand information for patients 
• Lack of access to hematology nurses 
• Time pressure in appointments

Tools for support  
Participants supported the use of patient decision aids (PtDAs)—simple tools that explain treatment options, pros and cons, and help patients clarify what matters most to them. Most felt these tools would make SDM easier.

Key recommendations

• Personalize involvement. 
Ask each patient how much they want to be involved—this can change over time—and revisit this regularly.

• Discuss all options, including “no treatment.” 
Patients should receive clear and honest information about all choices, including palliative care, when appropriate.

• Address feelings and fears. 
Doctors and nurses should ask about emotional concerns and refer patients to psychological or social support when needed.

• Create more awareness of SDM. 
Health professionals need more training, and patient organizations can help patients understand their right to be involved.

• Provide clear educational materials and decision aids. 
Information should be written in plain language and developed together with patients.

• Increase the role of hematology nurses. 
Nurses should be more involved in discussions about treatment options, as they often help patients understand and process information.

Strengths and limitations 
The study included many participants from different countries, giving a broad picture. However, people already interested in SDM may have been more likely to participate, and some vulnerable patients might have been underrepresented.

Conclusion 
Shared decision-making is happening in MM care, but not consistently. Asking patients about their preferences, discussing all options openly, and involving hematology nurses and patient organizations more fully could greatly improve the decision-making experience. Better decision aids and clearer information can help patients feel more confident, supported, and involved in their care.

Reference: 
Schoefs, E., Verbeke, C., Broekmans, J. et al. Patients and healthcare professionals’ perspectives on the implementation of shared decision making in multiple myeloma: a multinational qualitative study. BMC Med Inform Decis Mak 25, 432 (2025). https://doi.org/10.1186/s12911-025-03229-8 
 

Utilization of real-world evidence in regulatory approvals for multiple myeloma therapies — Blood Cancer Journal (November 2025)

Background 
Multiple myeloma (MM) is a rare and incurable blood cancer that often relapses after treatment. Because patients may need many different treatments over time, researchers and regulators are pushing for faster ways to evaluate new therapies.

Why is real-world evidence important? 
Real-world evidence (RWE) uses information collected from everyday clinical care (such as electronic health records) instead of traditional clinical trials. This type of data is especially useful in MM because:

• Many patients relapse frequently, making long, controlled trials difficult. 
• Treatment standards change quickly. 
• MM is rare, so it can be hard to run large, randomized studies. 
• Patients with advanced disease often have limited treatment options, making it challenging or even unethical to include a placebo or control group.

Regulatory agencies like the U.S. FDA and Europe’s EMA now accept RWE to help support approvals of new MM therapies.

RWE helps in two major ways:

1. Natural history studies 
These show what happens to patients who receive standard care, helping regulators understand unmet medical needs.

2. External comparator arms 
These act like a comparison group for single-arm trials (studies without a control group). They allow new treatments to be judged against real-world outcomes.

Recent approvals for therapies such as CAR-T cells (Abecma®, Carvykti®) and bispecific antibodies (elranatamab, linvoseltamab) included RWE to support their applications.

From 2021–2025: 
• 44% of all new MM approvals used RWE. 
• Most of these were in patients who had already received several prior treatments. 

What are the challenges? 
RWE must meet strict quality standards. Data must be:

• Relevant (the right patients, treatments, and outcomes) 
• Reliable (complete, accurate, and well-documented)

Regulators have rejected RWE submissions when:

• Data came from too many different sources, 
• Key clinical information was missing, 
• Follow-up differed between the real-world group and the clinical trial group.

Because of these challenges, RWE is often used to support (not replace) clinical trial evidence.

Future implications 
RWE will continue to play a growing role in developing and approving new MM therapies, especially for patients with advanced disease. To use RWE successfully, companies must work closely with regulators early on and ensure the underlying data is high quality and appropriate for the intended purpose.

Bottom line 
Real-world evidence is helping speed up access to new multiple myeloma treatments by filling gaps that traditional trials cannot easily address. High-quality data from real clinical practice can provide valuable insights, especially for patients with few remaining treatment options.

Reference: 
Taylor, L., Chen, A. & Pierre, A. Utilization of real-world evidence in regulatory approvals for multiple myeloma therapies. Blood Cancer J. 15, 210 (2025). https://doi.org/10.1038/s41408-025-01420-8   
 

Comparative Efficacy of Talquetamab vs. Real-World Physician’s Choice of Treatment in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: Updated Analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent — Advances in Therapy (November 2025)

What is the purpose of the study? 
People with relapsed or refractory multiple myeloma (RRMM) who have already been treated with the three main types of myeloma drugs (“triple-class exposed”) often have limited treatment options and poor outcomes. Talquetamab is a newer immune-based therapy that targets a protein called GPRC5D on myeloma cells. It is already approved for patients who have received many prior treatments.

This study compared how well talquetamab works versus the treatments doctors commonly use in real-world practice, using data from several clinical and observational studies.

How was the study conducted? 
• Researchers compared patients from the MonumenTAL-1 trial who received talquetamab with similar patients from two real-world studies (LocoMMotion and MoMMent) who received their doctor’s choice of treatment. 
• Three groups of patients were studied: 
    - No prior T-cell–redirecting therapy (two talquetamab dosing schedules) 
    - Prior BCMA-directed therapy (CAR-T or bispecific antibody) 
• Statistical methods were used to account for differences between the groups so the comparison would be fair.

Key findings

1. Patients with no prior T-cell–redirecting therapy

Compared with real-world treatments, talquetamab led to:

• Higher response rates (more patients’ cancer shrank) 
• Deeper responses (more very good or complete responses) 
• Longer time before the cancer worsened 
• Longer time before another treatment was needed 
• Improved overall survival

These results were similar with both talquetamab dosing schedules.

2. Patients who previously received BCMA-directed therapy (CAR-T or bispecific antibody)

Talquetamab still performed better than real-world treatments, with:

• Higher response rates 
• Much longer periods before cancer progression or death 
• Improved overall survival

This benefit was seen regardless of whether patients had received prior CAR-T or bispecific antibody treatment.

Long-term follow-up 
With over 2–3 years of follow-up in some groups:

• The benefit of talquetamab stayed consistent. 
• Median overall survival had not yet been reached in some talquetamab groups, suggesting durable benefit.

What this means for patients 
• Talquetamab offers stronger and longer-lasting disease control than the treatments typically used in real-world practice for people with heavily pre-treated multiple myeloma. 
• It appears effective both before and after BCMA-targeted therapies like CAR-T. 
• These results support talquetamab as an important treatment option for patients with limited remaining therapies.

Limitations 
• Real-world comparison groups included fewer newer therapies because many were not widely available at the time of the studies. 
• Safety differences were not evaluated in this analysis. 
• Some groups were small, especially patients with prior T-cell–redirecting therapy.

Bottom line 
Across multiple patient groups and with longer follow-up, talquetamab consistently outperformed commonly used real-world treatments for people with triple-class-exposed multiple myeloma, offering higher response rates and longer survival—even in patients who had already received advanced treatments like CAR-T.

Reference: 
Einsele, H., Moreau, P., Bahlis, N. et al. Comparative Efficacy of Talquetamab vs. Real-World Physician’s Choice of Treatment in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: Updated Analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent. Adv Ther (2025). https://doi.org/10.1007/s12325-025-03409-y

Characterizing circulating rare cells in peripheral blood for detecting and monitoring multiple myeloma and precursor states — npj Precision Oncology (December 2025)

Background 
Multiple myeloma (MM) is a cancer that develops from abnormal plasma cells. It usually starts as earlier conditions (MGUS or smoldering myeloma/SMM)—before progressing to full multiple myeloma. Today, detecting progression from these early stages often requires bone marrow biopsies, which are invasive and uncomfortable.

How was the study conducted? 
Researchers tested a liquid biopsy, a simple blood test, to look for small numbers of circulating plasma cells (PCs) in 68 patients across the disease spectrum (MGUS, SMM, newly diagnosed MM, and relapsed MM). They used advanced immunofluorescence imaging and machine learning to identify rare cancer-related cells.

Key findings 
• Circulating plasma cells were detected at increasing levels as disease became more advanced, from MGUS → SMM → overt MM. 
• A specific cell type (called D | CD138 | BCMA-Memb) was the best predictor of disease stage. 
• The test accurately distinguished early precursor conditions from active myeloma 86% of the time. 
• Changes in cell markers (BCMA and CD45) also reflected disease activity and the effects of previous treatment. 
• Results from blood samples correlated with standard bone marrow tests, showing biological consistency.

Why this study matters 
• A blood test could offer a non-invasive alternative to bone marrow biopsies. 
• It may allow earlier detection of progression, especially in MGUS and SMM, where identifying high-risk patients is a major challenge. 
• Regular blood-based monitoring could help track disease evolution, response to treatment, development of treatment resistance. 
• More comfortable testing for patients with fewer bone marrow biopsies. 
• More frequent monitoring, giving doctors real-time information about disease changes. 
• Potential for earlier treatment in patients at high risk of progressing from MGUS or SMM. 
• Better understanding of how MM cells change with treatment, helping guide personalized therapy.

Limitations & future directions 
• The study included a small number of patients, so larger studies are needed. 
• The test still needs further refinement to improve sensitivity and define clear thresholds for clinical use. 
• Longer follow-up is required to learn how well these circulating cell patterns predict survival. 
• Future research will combine this test with other blood-based markers (like cell-free DNA) for a more complete disease picture.

Takeaways for patients 
This study shows that a simple blood test can detect and characterize rare plasma cells associated with multiple myeloma. It has strong potential as a non-invasive tool to diagnose, monitor, and predict disease progression—especially in early stages—offering a more comfortable and informative alternative to bone marrow biopsies.

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

Enhanced Detection of Multiple Myeloma Cells by Next-Generation Flow Cytometry Following Density Gradient Medium Separation — European Journal of Haematology (December 2025)

Background 
Multiple Myeloma (MM) often returns because of measurable residual disease (MRD) that remains in the blood or bone marrow after treatment. As treatments improve and more patients reach remission, doctors need MRD tests that are faster, more sensitive, and more affordable.

What is the purpose of the study? 
Researchers compared three different ways of preparing blood or bone marrow samples to make MRD testing by flow cytometry more sensitive and efficient. They tested:

1. Bulk lysis (BL) – the current standard 
2. Density gradient medium (DGM) separation 
3. Negative selection (NS)

They analyzed samples from 32 patients with active MM and 122 patients in remission.

Key findings

• DGM separation was the most sensitive and practical method. 
     - It removes unnecessary white blood cells (mainly granulocytes), allowing laboratories to test more useful cells from each sample. 
     - Because of this, DGM detected much smaller amounts of MRD—meaning it can catch relapse earlier. 
     - DGM had a lower detection limit (better sensitivity) than the standard BL method.

• DGM was also faster and more cost-effective than the other methods. 
• Negative selection (NS) could process large cell numbers but was too expensive, slower, and lost important cells, making it unsuitable for routine clinical use. 
• The study did not recommend “positive selection” because it can damage cell markers needed for accurate MRD measurement.

Why this study matters 
• More sensitive MRD tests help doctors identify relapse earlier and guide treatment decisions. 
• A method that is faster and less expensive helps clinical laboratories handle increasing patient volumes. 
• Although DGM works well, its results don’t fit perfectly with current reporting standards, so clinical guidelines may need adaptation before DGM becomes routine.

Conclusion 
The DGM separation method improves sensitivity, reduces testing time, and lowers costs compared with the current standard method. It may become a valuable tool for monitoring MM patients, especially when larger sample volumes are needed, but adjustments in reporting practices will be required before widespread clinical use.

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

Outcomes of elranatamab in relapsed/refractory multiple myeloma: prognostic impact of monocyte count, MyCARe, and R2-ISS — International Journal of Hematology (December 2025)

What is the purpose of the study? 
Elranatamab is a newer type of immunotherapy called a bispecific antibody used for people with relapsed or refractory multiple myeloma (RRMM). Although clinical trials have shown good results, information from everyday medical practice (“real-world data”) is still limited.

This study looked back at how patients treated with elranatamab at one medical center actually did and explored factors that might predict who benefits most.

How was the study conducted? 
• 37 patients with advanced RRMM 
• Median age: 67 
• Average previous treatments: 5 different lines of therapy 
• Followed for 7.5 months on average

Key findings 
• 67.6% of patients responded to the treatment 
• 46% had a deep response (very good partial response or better) 
• Median progression-free survival: 9.7 months 
• One-year overall survival: 66.3%

These results are similar to earlier clinical trials, confirming elranatamab’s benefit in routine practice.

Certain factors were linked to shorter survival and quicker relapse: 
• Extramedullary disease (myeloma outside the bone marrow) 
• High-risk genetic features 
• Plasma cells found in the bloodstream 
• Low monocyte count (<300/µL) 
• High-risk categories on two risk-scoring systems: 
 - Modified MyCARe model 
 - Dynamic R2-ISS stage IV

Many of these features reflect weaker immune health, which may reduce the effectiveness of immunotherapies like elranatamab.

Safety profile 
The safety profile was similar to what clinical trials reported:

• Cytokine release syndrome (CRS) and infections were the most common side effects 
• One case of severe neurotoxicity (ICANS) occurred 
• Overall, side effects were manageable.

Why these results matter 
• Elranatamab is an effective real-world treatment option for heavily pretreated multiple myeloma. 
• Simple blood tests—like monocyte and lymphocyte counts—may help doctors predict how well a patient might respond. 
• Risk scoring systems used for other BCMA-targeted therapies may also help guide expectations with elranatamab.

Limitations 
• The study included small numbers and came from one center. 
• Follow-up time was limited. 
• Some important biological markers (like soluble BCMA) weren’t measured.

Conclusion 
Elranatamab shows strong real-world effectiveness for patients with difficult-to-treat multiple myeloma. Certain disease features and immune-related blood counts can help identify patients who may need additional or alternative treatment approaches. Larger studies are needed to confirm these findings and guide personalized treatment strategies.

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

Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis — Annals of Hematology (December 2025)

What is the purpose of the study? 
Extramedullary disease (EMD) is an aggressive form of multiple myeloma where the cancer spreads outside the bone marrow into soft tissues or organs. Patients with EMD often respond poorly to standard myeloma treatments.

This study combined data from nine clinical trials to better understand how patients with EMD do compared with those without EMD when treated with standard therapies.

How was the study conducted? 
Researchers analyzed results from older studies of standard treatments used for relapsed/refractory multiple myeloma—including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies like daratumumab.

They compared:

• 158 patients with EMD 
• 2706 patients without EMD

They looked at:

• Overall response rate (ORR): how many patients’ cancer shrank 
• Progression-free survival (PFS): how long until the cancer worsened 
• Overall survival (OS): how long patients lived

They also adjusted results for age, number of previous treatments, and disease stage.

Key findings 
Patients with EMD did much worse than patients without EMD on standard myeloma treatments:

1. Response rates

• 20.7% responded with EMD 
• 66.2% responded without EMD 
• Patients with EMD were 87% less likely to respond

2. Progression-Free Survival (PFS)

• 6.3 months with EMD 
• 12.9 months without EMD 
• Patients with EMD were almost twice as likely to have their cancer worsen sooner

3. Overall Survival (OS)

• 21 months with EMD 
• 39 months without EMD 
• Patients with EMD were almost twice as likely to die sooner

Importantly, among the small group of patients who did respond, how long the response lasted was similar in both EMD and non-EMD groups.

What does this mean? 
• Standard treatments do not work as well for patients with EMD. 
• EMD remains a high-risk condition with major unmet needs. 
• Achieving a response is crucial because responders can do reasonably well, but responses are harder to achieve.

Why are outcomes worse in EMD? 
EMD tumors often:

• Spread outside the bone using different biological pathways 
• Have genetic changes that make them more aggressive 
• Show less consistency in treatment targets like BCMA and GPRC5D

These features may make cancer more resistant to therapy.

How do newer treatments compare? 
Newer options like CAR-T therapy and bispecific antibodies show better response rates overall, but patients with EMD still have lower and shorter-lasting responses compared with those without EMD.

Examples:

• CAR-T response rates: 52–58% with EMD vs. 82–96% without 
• Bispecific antibodies: 31–49% with EMD vs. 68–74% without

Combination approaches (e.g., dual-target bispecific antibodies) are being studied and show early promise.

Limitations 
• Not all modern treatments were included. 
• Data on some patient characteristics were missing. 
• Some studies had small numbers of EMD patients. 
• Only “true EMD” was included (soft tissue tumors not touching bone).

Bottom line 
Patients with extramedullary disease have significantly worse outcomes on standard myeloma treatments. There is a clear need for more effective therapies—especially modern immune-based treatments like CAR-T and bispecific antibodies, which may offer hope for this high-risk patient group.

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

Clinical Trials
 

Shared Decision-Making in Treatment Selection in Multiple Myeloma in Spain: The PRISMMA Study — European Journal of Haematology (November 2025)

What is the purpose of the study? 
This study explored how patients with multiple myeloma and their hematologists in Spain view and experience shared decision-making (SDM)—that is, how both sides work together to choose the best treatment.

How was the study conducted? 
Two anonymous online surveys were completed: one by 72 hematologists and one by 76 MM patients. Questions focused on treatment goals, discussion of options, and who makes the final treatment decisions.

Key findings

• Shared main goal: Both patients and doctors agreed that the most important goal is to live longer while maintaining a good quality of life. 
• Second goals differed: 
   - Patients ranked being symptom-free next in importance. 
   - Doctors tended to prioritize quality of life over extending survival, especially in later treatment stages.

• Least important goal: Both groups agreed that reducing hospital visits mattered least. 
• Communication gap: 
   - While 92% of doctors said they discussed treatment goals with patients, only 17% of patients recalled such conversations. 
   - Most doctors said they offered several treatment options, yet 83% of patients said they were given only one.

• Decision-making gap: 
   - 85% of doctors believed decisions were made together. 
   - 65% of patients felt their doctor made the final decision alone. 
   - Still, 80% of patients were satisfied overall, showing trust in their doctor’s judgment.

What this means 
Although doctors and patients agree on the main treatment goal, their communication and perceptions differ greatly. Patients often feel less involved than doctors believe they are. Improving how treatment options and goals are discussed could help patients feel more empowered and ensure treatments match their values and needs.

Why this study matters 
When patients and doctors truly share decisions, it can improve treatment satisfaction, adherence, and well-being. Tools like structured discussion guides or visual aids could make these conversations clearer and more meaningful.

Limitations 
The study included a limited number of participants and may not fully represent all MM patients and doctors in Spain. Some responses may reflect memory or social bias.

Conclusion 
Patients and hematologists share similar priorities for MM treatment but differ in how they perceive discussions and decisions. Strengthening shared decision-making can help ensure each patient receives the most suitable, personalized care.

Reference: 
V. Cabañas, M. Casanova, B. Barragán, I. López, A. Raya, and B. Santiago-Josefat, “Shared Decision-Making in Treatment Selection in Multiple Myeloma in Spain: The PRISMMA Study,” European Journal of Haematology (2025): 1–10, https://doi.org/10.1111/ejh.70062. 

Integrated clinical and single-cell profiling of BCMA CAR-T therapy in relapsed/refractory multiple myeloma — Journal of Translational Medicine (November 2025)

Background 
Multiple myeloma remains incurable, especially when it comes back after treatment. A new therapy called BCMA-targeted CAR-T cell therapy—already approved by the FDA in some forms—uses a patient’s own immune cells to attack myeloma cells. However, access to these treatments can be limited, so this study tested a version made locally.

Study design 
Six patients with relapsed or hard-to-treat MM received locally made BCMA CAR-T cells. The main goals were to assess safety and how well the treatment worked.

Safety 
• 83% of patients developed mild cytokine release syndrome (CRS)—a temporary immune reaction managed successfully with medication (tocilizumab). 
• No serious side effects or nerve-related problems were observed. 
• Blood-related side effects were temporary and recovered quickly. 
• Overall, the treatment was considered safe and well-tolerated.

Effectiveness 
• 83% of patients responded to treatment. 
• 67% achieved a stringent complete response (no detectable disease). 
• Responses occurred even in patients with aggressive or high-risk disease. 
• After about 20 months of follow-up, most responders remained in remission. 
• The 12-month survival rate was 83%, and progression-free survival (PFS) was 67%.

Cell behavior and research findings 
Advanced single-cell studies showed that:

• The CAR-T cells remained in the body for several months and adapted over time. 
• Different groups of immune cells (CD8⁺ “fighter” cells) played specialized roles in attacking cancer. 
• Long-lasting remissions were linked to active and adaptable CAR-T cells, while relapse was associated with early T-cell exhaustion and immune-suppressing T cells (Tregs).

Conclusion 
Locally produced BCMA CAR-T therapy appears safe and highly effective for patients with multiple myeloma that has returned after several treatments. The immune analyses suggest that healthy, adaptable CAR-T cells and strong immune coordination are key for long-term success. Larger studies are needed to confirm these results and further improve CAR-T therapy.

Reference: 
Fang, C., Wang, L., Zhao, W. et al. Integrated clinical and single-cell profiling of BCMA CAR-T therapy in relapsed/refractory multiple myeloma. J Transl Med 23, 1251 (2025). https://doi.org/10.1186/s12967-025-07106-w 

Prognostic Impact of the Hevylite Assay in Patients with IgG or IgA Multiple Myeloma Treated Within the GMMG-MM5 Trial — European Journal of Haematology (November 2025)

Background 
In multiple myeloma, doctors track how well treatment is working by measuring abnormal antibodies (called paraproteins) in the blood using tests such as immunofixation or serum electrophoresis. However, these tests can struggle to measure very small amounts of certain paraproteins, especially IgA.

The Hevylite Assay is a newer blood test that separately measures two parts (called kappa and lambda) of the IgG and IgA antibodies. It can show whether these are balanced, which may indicate how well treatment is working.

In this study, researchers tested the Hevylite Assay on blood samples from 360 patients in the large German GMMG-MM5 clinical trial. Patients were followed through various stages of treatment, including chemotherapy, stem cell transplantation, and maintenance therapy.

The researchers found that:

• The number of patients with a normal Hevylite kappa/lambda ratio increased steadily during treatment. 
• Having a normal ratio by the end of consolidation therapy showed a trend toward longer time without disease worsening (called progression-free survival, or PFS), but this was not statistically significant. 
• There was no effect on overall survival (how long patients lived overall).

Interestingly, when patients were grouped by maintenance treatment: 
• Those who continued lenalidomide maintenance therapy and achieved a normal Hevylite ratio tended to stay in remission longer. 
• This effect was not seen in patients whose maintenance treatment stopped early.

These results suggest that the Hevylite test might be more informative for patients who continue long-term maintenance therapy and reach deep responses. However, overall, the test did not reliably predict how long patients would remain in remission or live.

The researchers note that newer, more sensitive methods—such as mass spectrometry (MS), next-generation flow cytometry, or cell-free DNA testing—can detect much smaller amounts of disease and may soon replace the need for the Hevylite test in most cases.

In summary 
• The Hevylite test measures abnormal myeloma proteins more precisely than older tests. 
• It showed some promise but wasn’t a strong or consistent predictor of treatment success. 
• It may still help in certain cases, but newer and more accurate blood tests are becoming available.

Reference: 
Richardson, T., Mai, E., Menis, E., Benner, A., Tichy, D., Miah, K., Hänel, M., Besemer, B., Boquoi, A., Blau, I.W., Michel, C.S., Lindemann, H.W., Janjetovic, S., Brossart, P., Bernhard, H., Reimer, P., Salwender, H., Hose, D., Seckinger, A., Raab, M., Goldschmidt, H., Scheid, C. and For the German-Speaking Myeloma Multicenter Group (GMMG) HD5 Investigators (2025), Prognostic Impact of the Hevylite Assay in Patients With IgG or IgA Multiple Myeloma Treated Within the GMMG-MM5 Trial. Eur J Haematol. https://doi.org/10.1111/ejh.70061

Linvoseltamab in Patients with Relapsed/Refractory Multiple Myeloma in the LINKER-MM1 Study: Longer Follow-Up and Subgroup Analyses — Clinical Lymphoma Myeloma and Leukemia (November 2025)

Summary 
Linvoseltamab is a new type of antibody treatment being studied for people with relapsed or refractory multiple myeloma (RRMM.

After about 21 months of follow-up, results from the LINKER-MM1 study showed: 
• Strong and lasting responses: 71% of patients responded to treatment, and over half (52%) had a complete response (no detectable cancer). Many of these deep responses lasted more than two years. 
• Effective in difficult cases: Linvoseltamab worked well even in patients with high-risk or advanced disease, including those who had already received many other treatments. 
• Survival benefits: Most patients were still living without their disease getting worse, and the average overall survival was about 31 months. 
• Manageable side effects: The most common were cytokine release syndrome (46%)—usually mild and seen early during dose increases—and low white blood cell counts (44%). 
• Fewer infections over time: Although infections were common early on, their rate dropped after the first six months of treatment. 
• No new safety concerns were found with longer follow-up.

Conclusion 
Linvoseltamab continues to show strong and lasting benefits for patients with hard-to-treat multiple myeloma, with side effects that are generally manageable and decrease over time.

Reference: 
Hans C. Lee, Jeffrey A. Zonder, Madhav V. Dhodapkar, Sundar Jagannath, James E. Hoffman, Attaya Suvannasankha, Mansi R. Shah, Suzanne Lentzsch, Rachid Baz, Joseph J. Maly, Swathi Namburi, Matthew J. Pianko, Jing Christine Ye, Ka Lung Wu, Rebecca Silbermann, Chang-Ki Min, Marie-Christiane Vekemans, Markus Munder, Ja Min Byun, Joaquín Martínez-Lopez, Michelle DeVeaux, Tito Roccia, Dhruti Chokshi, Megan Seraphin, Kate Knorr, Anita Boyapati, Anasuya Hazra, Karen Rodriguez Lorenc, Glenn S. Kroog, Naresh Bumma, Joshua Richter, Linvoseltamab in Patients with Relapsed/Refractory Multiple Myeloma in the LINKER-MM1 Study: Longer Follow-Up and Subgroup Analyses, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.11.004.

TSCM-predominant allogeneic anti-BCMA CAR-T therapy for relapsed/refractory multiple myeloma: preclinical characterization and interim results from a phase 1 trial — Nature Communications (November 2025)

Background 
P-BCMA-ALLO1 is an “off-the-shelf” CAR-T cell treatment being developed for people with relapsed/refractory multiple myeloma (RRMM). Unlike standard CAR-T therapy, which is made from each patient’s own cells, this treatment is made from healthy donor cells and can be given quickly after a patient enrolls.

How it works 
• The therapy targets BCMA, a protein found in multiple myeloma cells. 
• CAR-T cells are made to have many T stem-cell memory (TSCM) cells—long-lasting, flexible immune cells that can multiply and fight cancer over time. 
• These cells grow and change into “effector” cells after infusion, which directly attack cancer.

Early clinical results (Phase I) 
• 33 patients were treated; all received the infusion without needing “bridging” chemotherapy. 
• Among 11 patients who received stronger (enhanced) pre-treatment chemotherapy (lymphodepletion): 
   - 82% responded to therapy. 
   - Nearly two-thirds (63.6%) had a very good partial response or better. 
• The CAR-T cells expanded in the body around 10 days after infusion and were found in the bone marrow, where myeloma grows.

Safety 
• Side effects were generally mild. 
• Cytokine release syndrome (CRS) occurred in about 21% of patients, all grade 1–2 (low severity). 
• No severe neurologic effects or dose-limiting toxicities were reported. 
• Because of a good safety profile, treatment can be given as an outpatient.

Why TSCM cells matter 
• Lab and early clinical data show that having more TSCM cells in the product: 
   - Improves cancer-killing ability 
   - Supports long-term persistence of CAR-T cells 
   - May reduce side effects

• This memory-rich cell mix expands quickly after infusion and then becomes active cancer-fighting cells.

Advantages of “off-the-shelf” CAR-T 
• Ready when needed: patients can start treatment within days, not weeks or months. 
• Helps avoid delays or failures seen with manufacturing personalized (autologous) CAR-T cells. 
• Improves access for more patients.

What needs more research 
• Why stronger pre-treatment chemotherapy improves CAR-T expansion 
• The role of CD4 vs. CD8 T-cell balance in treatment success 
• How long donor-derived CAR-T cells persist and protect patients over time 
• How best to refine manufacturing to improve consistency and potency

Bottom line 
P-BCMA-ALLO1 is an allogeneic (donor-derived) CAR-T therapy showing promising early effectiveness, rapid availability, and a favorable safety profile for patients with relapsed or refractory multiple myeloma. Its strong performance appears linked to its high level of long-lasting T-memory stem cells, which enable robust cancer control with fewer severe side effects. Further study is underway.

Reference: 
Tseng, H., Dholaria, B., Cranert, S.A. et al. TSCM-predominant allogeneic anti-BCMA CAR-T therapy for relapsed/refractory multiple myeloma: preclinical characterization and interim results from a phase 1 trial. Nat Commun 16, 10050 (2025). https://doi.org/10.1038/s41467-025-65267-0 
 

Frail subgroups determine heterogeneous outcomes in older patients with NDMM: long-term follow-up of the HOVON 143 trial — Blood Advances (November 2025)

Background 
Frailty (not age alone) is a major factor affecting how well older adults with multiple myeloma (MM) respond to treatment.

What is the purpose of the study? 
The HOVON 143 trial focused on patients considered frail by using a standard frailty score (IMWG-FI).

Key findings 
• Overall outcomes for frail patients were limited. 
• Median survival was less than 3 years, even with modern combination therapy. 
• Not all frail patients are the same. Frailty can come from: 
  - Age over 80 alone, 
  - Health issues affecting daily functioning (geriatric impairments), 
  - Other medical conditions (comorbidities), or 
  - A combination of these.

• Patients frail due to health impairments or multiple issues had the poorest results. Many of these “ultrafrail” patients died early, often before their cancer progressed. 
• Patients who are frail only because of age (over 80) did better and had much lower early death rates.

Why this study matters 
• Current frailty tools may group very different patients together even though their risks differ widely. 
• A more precise frailty definition is needed to identify: 
 - Patients who might benefit from standard treatment, and 
 - Patients who need gentler, more personalized therapy.

Related research 
• Some trials are testing whether adjusting treatment doses based on frailty improves outcomes. Early results are mixed. 
• Different frailty tools (like the SFI) may misclassify patients, making it hard to compare results across studies. 
• Newer treatments such as CAR-T cells and bispecific antibodies look promising even in older adults, but data in frail and ultrafrail patients are still very limited.

Bottom line 
• Frail patients with multiple myeloma are a highly diverse group. 
• Those with multiple health impairments have the highest risk and need better-tailored, more tolerable treatments. 
• Future clinical trials must focus specifically on frail subgroups to improve care for those most vulnerable.

Reference: 
Febe Smits, Kaz Groen, Mark-David Levin, Claudia A. M. Stege, Roel van Kampen, Ellen van der Spek, Inger Nijhof, Yavuz M. Bilgin, Noortje Thielen, Inge Ludwig, Esther G. M. de Waal, Yorick Sandberg, Alain Kentos, Gert-Jan Timmers, Josien C. Regelink, Matthijs Westerman, Koen de Heer, Marie-Christiane Vekemans, Nazik Durdu-Rayman, Nicole C. H. P. de Graauw, Maarten R. Seefat, Niels W. C. J. van de Donk, Paula F. Ypma, Kazem Nasserinejad, Sonja Zweegman; for the HOVON 143 Study Group , Frail subgroups determine heterogeneous outcomes in older patients with NDMM: long-term follow-up of the HOVON 143 trial. Blood Adv 2025; 9 (22): 5828–5836. doi: https://doi.org/10.1182/bloodadvances.2025017394

Selinexor-based treatments are associated with increased expression of T-cell activation markers in multiple myeloma — Blood Immunology and Cellular Therapy (December 2025)

What is the purpose of the study? 
This study looked at how the multiple myeloma drug selinexor (SEL) affects both cancer cells and immune cells in the bone marrow. Researchers studied samples from patients treated in the STOMP clinical trial.

Key points 
• T cells (a type of immune cell) taken from patients after treatment with selinexor (SEL)–based regimens showed signs of activation and healthy growth, suggesting SEL may help support the immune system. 
• Myeloma cells from patients whose disease became resistant to SEL showed higher levels of PARP1, a protein involved in DNA repair, but did not show increases in immune “brakes” (immune checkpoints).

Findings

1. SEL may help activate T cells rather than exhaust them. 
  • After treatment, T cells showed increased levels of proteins linked to activation and attack against cancer, including granzyme B (a protein used to kill cancer cells). 
  • Importantly, T cells did NOT show increases in exhaustion markers like PD-1, LAG3, or CTLA-4, even in patients whose cancer eventually progressed. 
  • This means SEL does not seem to “wear out” T cells, which is important for patients who may receive immune-based treatments later—like CAR-T cells or bispecific antibodies.

2. SEL may be a good “bridging therapy.”

Because SEL appears to control myeloma, avoid damaging T cells, and possibly support T-cell function, it may be a useful treatment before or after advanced immune therapies, such as CAR-T or bispecific antibodies.

Early real-world reports show patients treated with SEL before CAR-T or after relapse from CAR-T often responded well to the next treatment.

3. Clues about why some myeloma cells resist SEL: 
  • Before treatment, myeloma cells with high levels of growth-related proteins (pMEK1 and pAKT) were more likely to resist SEL. 
  • Myeloma cells from patients who became resistant later showed higher levels of PARP1, a protein that helps repair DNA. 
  • This suggests PARP1 inhibitors (drugs already used in some cancers) might be useful to combine with SEL in the future.

Takeaways for patients  
• Selinexor not only fights myeloma directly but also appears to support healthy immune function. 
• It does not seem to “shut down” T cells, which is encouraging for patients considering CAR-T or bispecific antibody treatments. 
• Researchers are exploring ways to combine SEL with other therapies to improve outcomes, prevent resistance, and make immune-based treatments more effective.

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

U.S. Food and Drug Administration

FDA Grants Breakthrough Therapy Designation for Tecvayli (teclistamab) plus Darzalex Faspro (daratumumab and hyaluronidase-fihj) as a Second Line for Patients with Relapsed/Refractory Multiple Myeloma

On Tuesday, December 9, Johnson & Johnson announced via press release that the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation (BTD) for Tecvayli® (teclistamab-cqyv) plus Darzalex Faspro® (daratumumab and hyaluronidase-fihj) as early as a second line for patients with relapsed/refractory multiple myeloma (RRMM).

According to Johnson & Johnson, there is "new data from the investigational Phase 3 MajesTEC-3 study that demonstrate the potential of TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) as early as second line for patients with relapsed/refractory multiple myeloma (RRMM). Results show an 83% reduction in the risk of disease progression or death compared to standard regimens at nearly three-years follow-up (hazard ratio [HR], 0.17; 95 percent confidence interval [CI], 0.12-0.23; P<0.0001). Ninety-one percent of patients who were progression-free at six months remained progression-free at three years."

The MajesTEC-3 study "evaluated the efficacy and safety of the investigational immunotherapy combination of TECVAYLI® plus DARZALEX FASPRO® versus DARZALEX FASPRO® and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with RRMM who have received 1-3 prior lines of therapy."

This data was presented at the 2025 American Society of Hematology (ASH) Annual Meeting and published in The New England Journal of Medicine.  

Reference: 
Unprecedented results from the Phase 3 MajesTEC-3 study support TECVAYLI® plus DARZALEX FASPRO® as a potential standard of care as early as second line for patients with relapsed/refractory multiple myeloma, Johnson & Johnson press release, December 9, 2025.

FDA Awards National Priority Voucher to sBLA Application for Tecvayli and Darzalex Faspro Combination Based on MajesTEC-3 Trial Results

On Monday, December 15, Johnson & Johnson announced via press release that the U.S. Food and Drug Administration “has selected the teclistamab MajesTEC-3 supplemental Biologics License Application (sBLA) to participate in the Commissioner’s National Priority Voucher (CNPV) Pilot Program as it aligns with the program’s priority to deliver more innovative therapies for American people.”

“We’re on a mission to deliver more cures and meaningful treatments to the American people. This means proactively identifying potentially transformative therapies. Within hours of the results being published in the American Society of Hematology conference program, FDA leaders read the study, consulted with internal experts, and the following day contacted the company to discuss a national priority voucher. When a treatment demonstrates outstanding trial results, we have a duty to patients to move swiftly,” stated FDA Commissioner Marty Makary, M.D., M.P.H. in an FDA news release.

“The sBLA is based on the Phase 3 MajesTEC-3 results, which showed TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) demonstrated a statistically significant progression-free survival (PFS) and overall survival advantage compared to standard treatment after three years in patients with relapsed/refractory multiple myeloma. These results support the combination as a potential standard of care as early as second line. The U.S. FDA is reviewing the sBLA through the Real-Time Oncology Review (RTOR) program,” according to Johnson & Johnson.

Published in The New England of Medicine and presented as a late-breaking oral abstract (LBA-6) at the recently concluded American Society of Hematology (ASH) Annual Meeting, results of the MajesTEC-3 trial revealed that "patients with relapsed/refractory multiple myeloma who received a combination of teclistamab, a bispecific monoclonal antibody, and daratumumab, a CD38-directed monoclonal antibody, were 83% more likely to be alive without disease progression compared with those who received standard second-line therapies at a median of nearly 35 months of follow-up," stated ASH in a press release.

The Commissioner’s National Priority Voucher (CNPV) Pilot Program “offers an unprecedented opportunity to reduce drug and biological product application or efficacy supplement (ES) review times from 10-12 months to just 1-2 months. Announced in June 2025, this innovative program uses a collaborative tumor board style review process to accelerate approvals for companies aligned with critical U.S. national health priorities,” states the FDA.  

“The CNPV pilot program reflects the FDA's broader commitment to create more efficient approval processes and modernize regulatory frameworks for greater agility to meet emerging public health needs,” the FDA further said.

References: 
• TECVAYLI® plus DARZALEX FASPRO® combination selected for Commissioner’s National Priority Voucher Pilot program, Johnson & Johnson press release, December 15, 2025.

• FDA Proactively Awards National Priority Voucher Based on Strong Phase 3 Study Results, FDA news release, December 15, 2025.

• Costa LJ, Bahlis NJ, Perrot A, Nooka et al. MajesTEC-3 Trial Investigators. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2514663.

• María-Victoria Mateos, et al. Presentation ID LBA-6: Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. 67th ASH Annual Meeting Late-Breaking Abstracts Session, December 9, 2025.

• Tec-Dara Combination Offers Substantial Improvement Over Standard Second-Line Therapies for Relapsed or Refractory Multiple Myeloma, American Society of Hematology press release, December 9, 2025.

• Commissioner's National Priority Voucher (CNPV) Pilot Program, U.S. Food and Drug Administration. November 6, 2025.

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.