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.   

In this week’s blog, read about the latest clinical guidelines in myeloma, including guidelines on treatment options for myeloma patients from the National Comprehensive Cancer Network. Discover clinical applications of mass spectrometry in myeloma, as well as a 2025 review of idecabtagene vicleucel or ide-cel (Abecma®), and ciltacabtagene autoleucel or cilta-cel (Carvykti®) across clinical studies and real-world evidence. Find out the results of two iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) studies that were published in Blood Advances and Leukemia. Additionally, catch up on some of the latest in myeloma research, clinical trials and FDA approvals. 

 

Guidelines and Recommendations 

 

Prevention and treatment of venous thromboembolism in patients with multiple myeloma: Clinical practice guidelines on behalf of the European Myeloma Network — HemaSphere (August 2025) 

Background 
Blood clots (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), are common and dangerous complications in people with multiple myeloma. They can worsen quality of life, interrupt treatment, and reduce life expectancy. 

What the new EMN-VTE guidelines recommend 

1. Patient awareness 

• Know the risk: MM increases your risk for clots. 
• Learn the signs: Swelling, pain in the leg, or sudden shortness of breath could mean a clot. 
• Get help quickly: Early treatment is critical. 

2. Regular risk checks 
Doctors should regularly assess your risk of clotting and bleeding, using tools available—though these tools aren’t perfect. 

3. Preventing clots (Thromboprophylaxis) 
Most myeloma patients starting IMiD- or carfilzomib-based therapy should receive medication to prevent blood clots, no matter their initial risk score. 

Medications include: 

• Low-molecular-weight heparin (LMWH) (injection) 
• Factor Xa inhibitors (oral pills like apixaban or rivaroxaban) 
• Low-dose aspirin (only for those at very low risk) 

4. Treating diagnosed clots 
If a clot is diagnosed, treatment should begin immediately using LMWH or factor Xa inhibitors. 

Treatment usually lasts at least 6 months, with longer treatment depending on individual risk. 

 
5. Personalized long-term care 
Ongoing treatment decisions should be tailored to your disease status, response to therapy, bleeding risk, and personal preferences. 

Low-dose apixaban is preferred for long-term prevention after initial treatment. 

 
6. Specialized clinics 
The guidelines recommend setting up specialized outpatient clinics for MM patients at risk of or dealing with VTE, to improve care coordination and outcomes. 

 

Key takeaways for patients 

• Blood clots are a serious but manageable risk in myeloma. 
• Preventive treatment is often necessary—especially when starting specific myeloma therapies. 
• Talk to your healthcare team about your individual risk, symptoms to watch for, and which preventive or treatment options are best for you. 

 
Looking ahead 

More research is needed to: 

• Improve risk assessment tools. 
• Determine the best types and durations of clot-prevention treatment for myeloma patients. 

In the meantime, these guidelines help ensure myeloma patients receive consistent, evidence-based care to reduce the risk of blood clots and improve quality of life. 

 
Reference: 
Gerotziafas, G., Fotiou, D., Nijhof, I., Ay, C., Lecumberri, R., Laroca, A., Cook, G., Engelhardt, M., Zweegman, S., Delforge, M., Maraveyas, A., Lefkou, E., Marchetti, M., Van de Donk, N.W.C.J., Gay, F., Ludwig, H., Einsele, H., San Miguel, J.F., Dimopoulos, M.A., Boccadoro, M., Sonneveld, P., Falanga, A. and Terpos, E. (2025), Prevention and treatment of venous thromboembolism in patients with multiple myeloma: Clinical practice guidelines on behalf of the European Myeloma Network. HemaSphere, 9: e70177. https://doi.org/10.1002/hem3.70177  

 

NCCN guidelines focus on treatment options for patients with multiple myeloma — Cancer (August 2025) 

 

Summary 

The National Comprehensive Cancer Network (NCCN) has released new updates to guide doctors in treating multiple myeloma—a type of blood cancer. These updates cover diagnosis, treatment, and care after initial treatment. 

1. Understanding High-Risk Multiple Myeloma (HRMM) 
Patients are now more clearly categorized as high-risk or standard-risk based on new genetic and lab test findings. High-risk patients may have: 

• Certain genetic mutations (e.g., TP53 or del(17p)) 
• Chromosome changes (e.g., 1q+, t(4:14)) 
• High levels of a blood protein called β2-microglobulin with normal kidney function. 

Everyone else is considered standard risk. 

 

2. Diagnostic updates 

• New tests like kidney biopsies and advanced genetic sequencing help detect complications and tailor treatment. 
• Doctors are now encouraged to store bone marrow samples at diagnosis to track minimal residual disease (MRD) later. 

 

3. High-risk smoldering myeloma (HR-SMM) 
For patients with high-risk smoldering myeloma (early disease with high chance of progression), daratumumab can now be used to help delay progression to active cancer. 

 

4. Treatment for active myeloma 

• New regimens are recommended based on patient eligibility for a stem cell transplant (HCT): 

          - Transplant-eligible patients: A 4-drug combo called Isa-VRd (isatuximab, bortezomib, lenalidomide, dexamethasone). 
          - Not eligible or deferring transplant: Options include Dara-VRd or Isa-VRd for patients under 80 who aren’t frail. 

• For cancer that spreads to the brain or spine (CNS involvement), a combination of treatments is now suggested, including radiation, chemotherapy, and new therapies like CAR T-cell therapy. 

 

5. Maintenance and supportive care 

• Infection prevention: 

         - Start antibiotics like levofloxacin if white blood cells are very low. 
         - Use immunoglobulin if levels are low or infections keep recurring. 

• Consider tocilizumab before starting BsAb therapy to reduce side effects. 
• Bone care: Patients on denosumab should continue treatment for up to 2 years, with ongoing review. 

 

6. Treatment after relapse 

• Patients may receive more than one BCMA-targeted therapy, but response may be lower if used back-to-back. 
• Other treatment options include belantamab mafodotin (Blenrep®) 
• For those with cancer outside the bone marrow (extramedullary disease), a combination of talquetamab (Talvey®) + teclistamab (Tecvayli®) may be used. 

 

7. Special populations 

• For older adults: Doctors should use the Myeloma Frailty Score Calculator to guide care decisions. 
• African American and Black patients: 

          - Have the highest rates of myeloma. 
          - Often have different genetic features and treatment responses. 
          - Need better inclusion in clinical trials. 
          - May experience different side effects, such as skin changes or higher risk of cytokine release syndrome. 

 

Why these updated NCCN guidelines matter 
These updated guidelines aim to personalize treatment, improve outcomes, and address diversity and inclusion in care. Your doctor will use these recommendations, along with your individual health needs, to create the best treatment plan for you. 

 

Reference: 
Nierengarten, M.B. (2025), NCCN guidelines focus on treatment options for patients with multiple myeloma. Cancer, 131: e70014. https://doi.org/10.1002/cncr.70014

 

Assessment and treatment of frail patients living with multiple myeloma. A guideline on behalf of the UK Myeloma Research Alliance Frailty Group — British Journal of Haematology (September 2025) 

 

Background 
These guidelines were created by a UK group of experts focused on frailty in myeloma patients. They followed a structured method used by the British Society for Haematology and used an international system (called GRADE) to judge the quality of evidence and strength of recommendations. 

 

Why frailty matters in myeloma treatment 

• Between 25% and 54% of newly diagnosed myeloma patients are considered frail. 
• As the disease relapses, up to 74% may become frail—often because of both ageing and side effects from earlier treatments. 
• More research is needed to fully understand how frailty changes over time in myeloma patients. 
• Most clinical trials focus on general treatment benefits but not enough on how to adjust treatments for frail patients. 
• Frailty affects how well someone tolerates treatment and recovers, so personalizing treatment based on frailty is key. 
• Frailty isn’t fixed — it can improve or worsen with treatment: About 15% of older patients improve after 1 year, but 33% may become frailer. 
• Many older patients (especially over 70) prioritize quality of life—like staying mentally sharp and physically able—over simply living longer. 

 

Frailty tools in myeloma 

These tools help predict how well a patient might tolerate treatment or recover. 

1. IMWG Frailty Score (IMWG-FS) – Gold Standard 

• Based on physical function, age, and health conditions. 
• Groups patients into fit, intermediate-fit, or frail. 
• Frail patients are more likely to have side effects and shorter survival. 
• It’s accurate but takes time (5–7 minutes), so it is not always practical in busy clinics. 

2. Modified IMWG Frailty Score 

• A simpler version used in some studies and clinics. 
• Easier to use but less detailed. 
• May misclassify patients by over- or underestimating frailty. 

3. Revised Myeloma Co-Morbidity Index (R-MCI) 

• Includes tests like lung function and genetic data about the myeloma. 
• Developed for younger, transplant-eligible patients. 
• Not always useful for older or less fit patients. 

4. UK Myeloma Risk Profile (UK-MRP) 

• Based on large UK trials. 
• Classifies patients as low, medium, or high risk. 
• Useful, quick, and validated in large studies, but may sometimes miss frailty signs. 

5. Mayo Clinic Frailty Score 

• Based on real-world patient data. 
• Similar to other tools but tends to place more people in the "intermediate risk" group. 

 

Clinical practice recommendations for NDMM 

 

• Use the full IMWG Frailty Score for newly diagnosed myeloma patients when possible. 
• Use simplified tools like the modified IMWG score or UK-MRP if time is limited. 
• Consider frailty assessments for patients with relapsed/refractory myeloma, although this is still being researched. 

 

Clinical practice recommendations for myeloma patients not receiving transplants 

 

Frailty assessment should be done for all patients not receiving a transplant at diagnosis. 

1. Fit patients under 80 can usually tolerate a 4-drug regimen (e.g., Dara-VRd). 
2. Intermediate-fit, frail, or over-80 patients may do better with a 3-drug combo like DRd, which is effective and better tolerated. 
3. Steroids can often be reduced or stopped early (after 2 cycles or if good response is achieved). 
4. Start with lower doses for frail or intermediate-fit patients and adjust treatment based on how they’re doing. 
5. For patients with kidney problems, certain drug doses (like lenalidomide, melphalan, or cyclophosphamide) should be further reduced. 

 

Early treatment in older/frailer patients with relapsed/refractory myeloma (RRMM) 

 

• Relapsed multiple myeloma (MM) can worsen frailty in older adults. 
• Starting treatment early—when blood tests show signs of relapse (biochemical progression)—can help prevent further decline. 
• Even in older or less fit patients, three-drug combinations (triplets) are usually better than two-drug combinations (doublets) and often well-tolerated. 
• When the disease progresses, switching to a different drug class and adding newer treatments (like monoclonal antibodies) is recommended. 
• It’s important to adjust treatment based on frailty level and side effects. 

 

New and promising treatments 

These advanced therapies are showing great success but come with specific side effects that must be carefully managed, especially in frail patients: 

1. Belantamab mafodotin (antibody drug conjugate) 

• More effective than some standard treatments. 
• Main side effect: eye problems, including blurred vision. 
• Most eye issues go away over time, but they could still affect daily living, especially in older patients. 

2. Bispecific antibodies (e.g., elranatamab, teclistamab, talquetamab) 

• Very effective in heavily pre-treated patients. 
• Key risks: infections, cytokine release syndrome (CRS), and neurological side effects (ICANS). 
• Infection risk is higher in frail patients, but giving immunoglobulin replacement and spacing out doses can help. 
• Talquetamab can cause skin changes, taste changes, weight loss, and nail changes—which may be harder on underweight or malnourished patients. 

3. CAR T therapy 

• Offers high response rates, even after many previous treatments. 
• Less common in routine care but promising for the future. 
• Side effects include CRS, neurological symptoms, and increased risk in frail patients. 
• Early studies suggest similar effectiveness in older adults, but frail patients may experience more complications and shorter survival. 

 

Clinical practice recommendations for supportive care 

 

1. Start treatment early when blood signs show progression. 
2. Adjust doses to reduce side effects and improve tolerance. 
3. Choose drug combinations based on how well they're tolerated in frail patients. 
4. Use newer therapies with caution in older/frailer patients, but don’t avoid them solely due to age. 
5. Minimize side effects through strategies like: 

        a. Spacing out doses (e.g., for belantamab or bispecific antibodies) 
        b. Giving immunoglobulin replacement 
        c. Monitoring nutrition and weight in patients on certain treatments 

     6. Always include supportive care at every stage. 

With careful planning and supportive care, even frail or older patients can safely receive effective myeloma treatments. The goal is to balance treatment benefits with side effect management to maintain quality of life. 

 

Future care  

 

1. Better assessment tools 
The Comprehensive Geriatric Assessment (CGA) is the best tool for evaluating frailty. It looks at: 

• Physical function 
• Other medical conditions 
• Falls 
• Nutrition 
• Memory and mental health 
• Medications and social support 

This approach gives a full picture of a patient’s health, beyond just age or blood test results. 

2. Team-based care 

• Future care models aim to bring together a team of specialists (doctors, nurses, physiotherapists, dietitians, pharmacists, social workers, etc.) to support frail patients. 
• Though resources may be limited, even partial adoption of this team-based model can improve care. 

3. Holistic support  

• Exercise programs, emotional support, and better communication can help patients manage frailty. 
• Tools like patient surveys (PROMs) and wearable devices may help detect early warning signs of health decline. 

4. Addressing psychological and social challenges 

• Many myeloma patients and their caregivers experience anxiety, depression, and stress. 
• Emotional support, managing caregiver fatigue, and removing practical barriers (like financial or memory issues) are just as important as managing the disease itself. 

5. Real-world evidence and frailty-focused trials 

• Most clinical trials don’t include the frailest patients. However, new trials (like Myeloma XIV "FiTNEss" and iFIT) are starting to focus on this group. 
• These studies aim to find the best ways to treat older or ultra-frail patients with tailored, flexible approaches. 

6. Ultra-frail patients 

• This group is the most vulnerable and hardest to treat. 
• For some of these patients, frailty may be more dangerous than the cancer itself. 
• New research (e.g. ULTRA FRAIL-MM trial) is exploring gentler, slower treatment plans for these individuals. 

7. Science and Innovation 

Researchers are exploring exciting new areas that may help reduce frailty: 

• Senolytics: Drugs that may slow aging and improve resilience (e.g. metformin, quercetin). 
• Sarcopenia: Muscle loss linked to frailty—but it can improve with exercise and nutrition. 
• Gut microbiome: A healthier gut (e.g. through a Mediterranean diet) may reduce frailty. 
• Metabolomics: Studying the body’s chemicals (like amino acids) may help us understand and manage frailty better. 

 

Why these guidelines matter 
Frailty plays a major role in how myeloma affects older adults. Better tools, personalized care plans, emotional support, and ongoing research are shaping a future where frail patients can receive safer, more effective treatment. Understanding and addressing frailty is just as important as treating the myeloma itself. 

 

Reference: 
Moore S, Miller H, Parrish C, Seymour F, Miller L, Chandler T, et al. Assessment and treatment of frail patients living with multiple myeloma. A guideline on behalf of the UK Myeloma Research Alliance Frailty Group. Br J Haematol. 2025; 00: 1–13. https://doi.org/10.1111/bjh.70041 

Minimal Residual Disease Negativity as the Primary Goal of Multiple Myeloma Therapy — Drugs (September 2025) 

 

Background 
Minimal residual disease (MRD) testing provides more accurate information about disease status than traditional methods. Patients who are MRD-negative usually have better outcomes. Repeated MRD tests over time (using bone marrow, blood, and imaging) give a more complete picture of the disease. 

 

How is MRD testing changing treatment? 
Clinical trials are using MRD to adjust treatment: 

• De-escalation: Stopping or reducing treatment in patients with MRD negativity. 
• Escalation: Adding treatment in patients with MRD positivity. 

MRD may help determine if a patient can safely avoid a stem cell transplant or stop maintenance therapy. 

 

Challenges with MRD testing 

• Access: High-sensitivity MRD tests aren’t available everywhere, and repeated bone marrow biopsies can be uncomfortable. 
• Cost and complexity: Testing can be expensive, and results may be hard to interpret. 
• Lack of guidelines: More research is needed to decide the best timing and how to act on MRD results. 

 

MRD positivity and resurgence 
If MRD remains positive or returns (resurgence), it may signal that the cancer will return—even before symptoms appear. 

Trials are ongoing to find out if changing treatment early (based on MRD resurgence) can delay or prevent relapse. 

 

Is MRD testing ready for everyday use? 
Many doctors are already using MRD results to help guide treatment decisions. For some patients—especially those with standard-risk disease—MRD negativity at a very sensitive level (10⁻⁶) may allow safe treatment reduction. 

However, in high-risk patients, stopping treatment (even with MRD negativity) can be risky. 

 

Looking ahead 

• Future studies will clarify when and how to use MRD results in real time. 
• Blood-based MRD tests may soon reduce the need for invasive bone marrow biopsies. 
• Better tools and training are needed so all patients and doctors can benefit from MRD-guided care. 

Why MRD testing matters 
MRD testing is a powerful tool in managing multiple myeloma. It helps identify patients who may need more or less treatment, aiming for the best outcomes with the least side effects. While more research is needed, MRD is leading the way toward personalized and adaptive treatment in myeloma care. 

 

Reference: 
Cooperrider, J.H., Derman, B.A. Minimal Residual Disease Negativity as the Primary Goal of Multiple Myeloma Therapy. Drugs (2025). https://doi.org/10.1007/s40265-025-02232-7 

 

Review 

 

Protocol for a scoping review of time to treatment in adults with newly diagnosed multiple myeloma — PLOS One (August 2025) 

 

Background 
In many types of cancer, delays in starting treatment can make the disease worse and reduce chances of survival. These delays can allow tumors to grow, cause more symptoms, damage organs, and increase emotional stress. While clear guidelines exist for when to start treatment in cancers like breast, colon, and lung cancer, no such guidelines exist for multiple myeloma. 

 

What is the purpose of the review? 
This study aims to explore what is currently known about how delays between diagnosis and starting treatment (called Time to Treatment Initiation, or TTI) affect people with newly diagnosed multiple myeloma. 

Although myeloma treatments have improved greatly since the year 2000, we still don’t know enough about how treatment timing impacts outcomes. Early evidence suggests that delays in myeloma treatment can worsen symptoms, cause organ damage, and reduce the time patients stay in remission. 

Researchers will: 

• Look at existing studies since 2000 on when treatment starts after diagnosis in MM. 
• Identify how TTI is defined and measured. 
• Examine how long patients usually wait before starting treatment. 
• Explore reasons for treatment delays. 
• Review how delays affect patient outcomes like survival, disease progression, and symptoms. 
• Highlight gaps in current research to guide future studies. 

 

How will the review be conducted? 

• A team will search major medical research databases (like PubMed and Embase). 
• They will include studies that focus on adults newly diagnosed with MM. 
• Only studies with available English translations and published since 2000 will be used. 
• Two independent reviewers will screen and select studies to make sure the review is accurate and unbiased. 

 

Why this review matters  
This review is the first step toward creating clinical guidelines for when myeloma treatment should begin. Better understanding of treatment timing can lead to improved care and outcomes for patients with multiple myeloma. 

Reference: 
LeBlanc MR, Taylor AO, Ansah OO, Conklin J. Protocol for a scoping review of time to treatment in adults with newly diagnosed multiple myeloma. PLOS One. 2025 Aug 25;20(8):e0330907. doi: 10.1371/journal.pone.0330907. 

 
From Physician-Driven to Patient-Centered: Transforming Multiple Myeloma Care Decisions — JCO Oncology Practice (September 2025, Editorial) 

What is the purpose of this editorial? 
This editorial on the accompanying original report, Patient Preferences on Clinical Decision Making in Multiple Myeloma, talks about improving myeloma outcomes and why patient voices matter. 

Over the past decade, survival for people with multiple myeloma has improved significantly.  New treatments are approved more quickly now, often based on early results like: 

• Progression-Free Survival (PFS) – how long patients live without the disease worsening 
• MRD negativity – a sign of deep treatment response 

However, many of these treatments are approved before we know if they help patients live longer overall (OS). Waiting for this long-term data can delay access to promising treatments. Still, these early markers (called surrogate endpoints) don't always predict better long-term survival, and they may not reflect what truly matters to patients. 

 

Survival vs. Quality of Life 
Modern myeloma treatments are often ongoing, with no clear end. This can cause: 

• Financial stress (cost of drugs, time off work) 
• Emotional burden (anxiety, depression) 
• Time toxicity (frequent appointments that reduce personal time) 

While clinical trials focus on PFS and MRD, they often miss patient concerns like: 

• Side effects 
• Impact on daily life 
• Whether the treatment improves overall survival 
• Quality of life during and after treatment 

 

What do patients really want? 

• Quality of life was the top priority for nearly half (49%) 
• Side effects were a major concern for 35% 
• Only 23% said they’d accept more side effects or burden unless the treatment extended life (OS) 
• Many patients were not interested in more treatment if it only added a couple of months without improving overall survival 

Preferences also changed over time: 

• Newer patients or those with higher education tended to prefer aggressive treatments 
• Longer-term survivors often preferred less intensive approaches 

This study shows a disconnect between clinical trials and real patient values. Trials often: 

• Focus on short-term data (PFS/MRD) and ignore long-term side effects 
• Don’t report real-world patient experience 
• Fail to include tools that measure emotional, financial, or lifestyle impact 

To truly improve myeloma care: 

• Clinical trials should include patient-reported outcomes like fatigue, anxiety, daily functioning, and financial stress 
• Patients and doctors should have honest conversations about what matters most—not just living longer, but living better 
• Treatment decisions should reflect both medical benefits and patient preferences 
• As treatments for myeloma continue to improve, it’s time to also focus on what patients value most—living longer, yes, but also living well. 

 

Reference: 
Richa Thakur et al. From Physician-Driven to Patient-Centered: Transforming Multiple Myeloma Care Decisions. JCO Oncol Pract 0, OP-25-00712 DOI:10.1200/OP-25-00712 

 

Clinical applications of mass spectrometry in multiple myeloma – Blood Advances (September 2025) 

 

What is the purpose of this review? 
This review discusses the clinical applications and advancements of mass spectrometry in the detection and monitoring of multiple myeloma, highlighting its sensitivity compared to traditional methods. 

 

Clinical applications in myeloma 
Mass spectrometry (MS) is revolutionizing the detection and monitoring of monoclonal proteins in multiple myeloma, offering enhanced sensitivity compared to traditional methods. 

• Detects and quantifies monoclonal proteins in peripheral blood with sensitivity orders of magnitude greater than serum protein electrophoresis (SPEP) and immunofixation. 
• Intact light chain (top-down) and clonotypic peptide (bottom-up) MS approaches show sensitivity comparable to or surpassing bone marrow (BM) assessments. 
• MS assays have transitioned from research to commercial availability, providing non-invasive monitoring tools that reduce reliance on BM biopsies. 

 

Advancements in peripheral blood assessments 
The development of liquid biopsies and MS has improved the sensitivity of MRD detection in multiple myeloma. 

• Liquid biopsies using next-generation sequencing (NGS) and next-generation flow cytometry (NGF) face challenges due to low circulating MM cells. 
• MS can detect monoclonal gammopathies at a sensitivity level surpassing SPEP/IFX, enabling frictionless, serial monitoring of disease. 
• MS is particularly relevant for achieving sustained MRD, necessitating frequent measurements. 

 

Prognostic value  
MS has demonstrated superior prognostic capabilities compared to traditional methods and BM MRD assays. 

• Studies show that MS can detect paraprotein where SPEP/IFX cannot, translating to better prognostication. 
• In trials, MALDI-MS showed 83% agreement with BM NGS, with LC-MS detecting residual disease cases missed by NGS. 
• Combining MS with BM assessments enhances prognostic accuracy, particularly in newly diagnosed patients. 

 

Monitoring disease progression  

MS can serve as an early indicator of disease progression in multiple myeloma. 

• Biochemical progression, defined by increased monoclonal protein levels, is critical for treatment decisions. 
• MS can detect changes in monoclonal protein levels earlier than conventional methods, potentially guiding treatment adjustments. 
• Studies indicate that MS positivity after maintenance therapy correlates with poor prognosis. 

 
 

Defining ‘cure’ in myeloma 
MS may contribute to defining a cure in multiple myeloma by identifying long-term disease control. 

• "Double negative" status by LC-MS and BM MRD may indicate patients with sustained disease control. 
• The sensitivity of clonotypic peptide MS could further refine definitions of cure in myeloma. 
• Multimodal MRD assessments are essential for guiding treatment decisions and defining long-term outcomes. 

 
 

Additional clinical applications  

• MS can distinguish therapeutic monoclonal antibodies from endogenous paraproteins, improving response assessments. 
• It can also detect disease in nonsecretory or oligosecretory patients, facilitating monitoring. 
• MS routinely identifies post-translational modifications like N-glycosylation, which have clinical implications for disease progression. 

 

Limitations and considerations  

• Delayed clearance of monoclonal proteins can confound MS results, particularly in assessing treatment response. 
• The requirement for baseline samples in clonotypic assays limits their applicability in many patients. 
• Understanding the optimal timing for MS testing is crucial for accurate interpretation of results. 

 

Advantages in MRD assessment 
MS provides a non-invasive and patient-friendly method for monitoring MRD in multiple myeloma. 

• MS allows for more frequent and dynamic monitoring without the need for bone marrow aspirations. 
• Patients prefer non-invasive methods, making MS a welcome change in their treatment regimen. 
• MS can help determine sustained MRD negativity, guiding treatment de-escalation decisions. 

 

Ongoing research and future directions 
Continued research is essential to fully realize the potential of mass spectrometry in multiple myeloma care. 

• Research will focus on comparing the costs of MS with other MRD assessment methods. 
• Further studies are needed to incorporate MS effectively into routine MM care. 
• The promise of MS in MRD assessment is contingent on ongoing advancements and validation in clinical settings. 

 

Reference: 
Benjamin A. Derman, Andrew J. Yee; Clinical applications of mass spectrometry in multiple myeloma. Blood Adv 2025; bloodadvances.2024015685. doi: https://doi.org/10.1182/bloodadvances.2024015685 

 

 
From Trials to Practice: A 2025 Review of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel Efficacy Across Clinical Studies and Real-World Evidence — European Journal of Haematology (September 2025) 

 

What is the purpose of the review? 
This 2025 review discusses the efficacy and real-world evidence of BCMA-directed CAR T-cell therapies: idecabtagene vicleucel or ide-cel (Abecma®), and ciltacabtagene autoleucel or cilta-cel (Carvykti®), in the treatment of relapsed/refractory multiple myeloma based on clinical trials and real-world evidence. 

 

How effective are these treatments? 

 

1. Ide-cel  

• Response rate: About 73%–89% of patients responded to treatment, even those who had many prior therapies. 
• Progression-free survival (PFS): On average, patients lived about 9–13 months without disease worsening. 
• Best results: Seen in patients who received higher doses or had fewer prior treatments. 
• Real-world data: Similar benefits were seen outside of clinical trials, including in older and frail patients. 

 

2. Cilta-cel 

• Response rate: Up to 98% of patients responded, with over 60% achieving complete remission. 
• PFS: Many patients remained disease-free for 2–3 years or longer. 
• Earlier treatment leads to better results – patients treated sooner after diagnosis had longer remissions. 
• Real-world use: Very effective even in patients who would not qualify for clinical trials. 

 

Side effects 
The most common serious side effects of CAR T-cell therapy include: 

• Cytokine Release Syndrome (CRS): An immune reaction that may cause fever, low blood pressure, or difficulty breathing. It occurs in 75–95% of patients but usually mild to moderate. 
• Neurotoxicity (Brain-related side effects) 

          - Symptoms: Confusion, speech changes, memory issues, or seizures. 
          - Seen in 15–21%, usually mild and short-lived. 

 

Other side effects 

• Low blood counts (anemia, neutropenia, thrombocytopenia) 
• Infections (especially respiratory) 
• Fatigue 
• Rare but possible: second cancers, including blood or skin cancers 

 

Key points for patients 

 

• High response rates, even in patients who've tried many other treatments. 
• Better results when used earlier in the disease course. 
• Real-world data confirms safety and effectiveness, even in older, frail, or diverse patient groups. 
• Side effects are common but mostly manageable, and teams are well-prepared to treat them. 

 

Who benefits the most? 

• Patients with relapsed or refractory multiple myeloma 
• Those who have had at least 3 prior therapies 
• Patients without active brain involvement or certain other exclusions (though newer data shows expanding eligibility) 

 

Challenges and considerations 

• Access to CAR T-cell therapy can be limited due to cost, hospital capacity, or waitlists. 
• Close follow-up is needed for side effects. 
• Not a cure but offers a potentially long remission in difficult-to-treat myeloma. 

 

Why ide-cel and cilta-cel matter 
CAR T-cell therapies like ide-cel and cilta-cel are transforming treatment for multiple myeloma. While not without risks, they offer hope for patients who have few options left. Ongoing research continues to improve outcomes and expand access. 

 

Reference: 
H. G. Pleitez, S. Saowapa, A. O. Maldonado, C. Kanitthamniyom, D. O. Bernal, and L. Tijani, “ From Trials to Practice: A 2025 Review of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel Efficacy Across Clinical Studies and Real-World Evidence,” European Journal of Haematology (2025): 1–14, https://doi.org/10.1111/ejh.70025. 

Research 

Next-generation flow cytometry analysis of clonal bone marrow plasma cells identifies an indolent subset of MGUS — Blood Advances (August 2025, Letter) 

 

What is the purpose of the study? 
This letter discusses the identification of an indolent subset of MGUS using next-generation flow cytometry analysis. The study identifies clonal bone marrow plasma cells in MGUS using next-generation flow cytometry (NGF).   

 

How was the study conducted? 

• The study was part of the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) trial, screening 75,422 adults in Iceland for MGUS.   
• 122 participants with IgA and/or IgG M-protein underwent NGF analysis.   
• Bone marrow samples were processed using standardized EuroFlow protocols. 

 

Key findings 

• Clonal plasma cells were detected in 84.4% of individuals, with higher detection in IgA MGUS (93.3%) compared to IgG MGUS (71.2%).   
• Among 40 MGUS individuals with repeat sampling, 34 remained clonal-positive.   
• Detection correlated with MGUS risk score, increasing from 43.2% in low risk to 100% in high-intermediate risk.   

 

Clinical implications 

• Absence of detectable clonal plasma cells indicates an indolent MGUS subset with transient or stable low-level IgG M-proteins.   
• Over 6.2 years, 52.6% of clonal-negative individuals had transient M-proteins, while 19.4% of clonal-positive individuals progressed to more advanced disorders.   

 

Why this study matters 
NGF-based detection can identify MGUS individuals unlikely to require ongoing monitoring, providing insights into isotype-related differences in progression risk. 

 

Reference: 
Jon Thorir Oskarsson, Sigrún Thorsteinsdóttir, Sæmundur Rögnvaldsson, Andri Ólafsson, Gunnhildur Viðarsdóttir, Elfa Rún Guðmundsdóttir, Elias Eythorsson, Asbjorn Jonsson, Bryjnar Vidarsson, Pall T Onundarson, Bjarni A Agnarsson, Margret Sigurdardottir, Ingunn Þorsteinsdóttir, Isleifur Olafsson, Stephen Harding, Brian G.M. Durie, Thorvardur Jon Love, Sigurdur Yngvi Kristinsson; Next-generation flow cytometry analysis of clonal bone marrow plasma cells identifies an indolent subset of MGUS. Blood Adv 2025; bloodadvances.2025017270. doi: https://doi.org/10.1182/bloodadvances.2025017270 

 

Challenging the Concept of Functional High-Risk Myeloma through Transcriptional and Genetic Profiling — Blood (August 2025) 

 

What is the purpose of the study? 
The study discusses functional high-risk multiple myeloma (FHR-MM), highlighting the importance of comprehensive genetic and transcriptional profiling in identifying patients at risk of early relapse. 

 

How was the study conducted? 
The study analyzed a uniformly treated cohort from the UK NCRI Myeloma XI trial to assess the prevalence of functional high-risk multiple myeloma (FHR MM) using comprehensive profiling.   

• 135 transplant-eligible patients from the MyXI trial were included, all receiving autologous stem-cell transplantation and lenalidomide maintenance. 
• The median follow-up period was 88 months.   
• Patients were profiled for high-risk cytogenetic aberrations and gene expression profiling (GEP).   

 

Key takeaways 

• Unexpected early relapse in multiple myeloma without known high-risk features is very rare when patients receive thorough testing at diagnosis. 
• “Functional high-risk” refers to patients who relapse early (within 18 months) despite appearing low risk at diagnosis. But this depends on what tests were done and what treatment was given. 
• In a UK clinical trial (Myeloma XI), only 2 out of 135 patients (1.5%) had true FHR MM when both genetic (cytogenetic) and gene activity (transcriptional) testing were used. 
• A gene activity test called SKY92 (also known as GEP-HR) helped find additional high-risk patients that standard genetic tests missed. 
• Combining both genetic and gene activity testing identified 84% of early relapses, allowing doctors to better predict who is truly high-risk. 
• Patients with both types of high-risk markers had the shortest survival, showing the importance of comprehensive testing at diagnosis. 

 

Why this study matters 
Thorough genetic and gene activity testing at the start of treatment can better identify patients at risk for early relapse in multiple myeloma, helping guide more personalized care. 

 

Reference: 
Sina Alexandra Beer, David A Cairns, Charlotte Pawlyn, Amy Elizabeth Holroyd, Elsa Ferris, Gordon Cook, Mark Drayson, Kevin D Boyd, Paula Zuzanna Proszek, Faith E Davies, Ruth M de Tute, Matthew W Jenner, Gareth J Morgan, Roger G. Owen, Michael J Hubank, Richard S. Houlston, Graham H Jackson, Martin F Kaiser; Challenging the Concept of Functional High-Risk Myeloma through Transcriptional and Genetic Profiling. Blood 2025; blood.2025029987. doi: https://doi.org/10.1182/blood.2025029987 

 

Impact of Dara-VTD induction therapy on stem cell mobilization outcomes in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation: a multicenter study — Annals of Hematology (September 2025) 

 

Background 
For patients newly diagnosed with multiple myeloma (NDMM), a common and effective treatment is a combination of chemotherapy followed by an autologous stem cell transplant (ASCT). One powerful treatment before transplant is Dara-VTD, which combines daratumumab with bortezomib, thalidomide, and dexamethasone. However, there have been concerns that daratumumab might make it harder to collect enough stem cells for transplant. 

 

What is the purpose of the study? 
To find out whether daratumumab affects the ability to collect stem cells needed for a successful transplant, and how to best manage this process. 

 

Key findings 

• Stem cell collection was successful in most patients treated with Dara-VTD. 

          - 96% collected enough stem cells for transplant. 
          - Median stem cell count was 5 million cells per kg of body weight. 

• Mobilization support (to help release stem cells from the bone marrow): 

          - The drug plerixafor was needed more often in the Dara-VTD group than in older treatment groups (56% vs. 4%). 
          - Using cyclophosphamide (CTX) helped improve stem cell yield. 

• Transplant outcomes were not worse with Dara-VTD. In fact, recovery of white blood cells and platelets was faster after transplant compared to older regimens. 
• Factors that affected success include: 

          - Stage of the disease (more advanced disease made mobilization harder). 
          - Previous treatments. 
          - Type of mobilization regimen used (CTX worked better than chemo-free approaches). 

 

Why does daratumumab make mobilization harder? 

Daratumumab targets a protein called CD38, found on myeloma and other bone marrow cells. While effective against the cancer, it can: 

• Interfere with how stem cells are released from the bone marrow. 
• Affect the bone marrow environment needed for stem cell growth and movement. 

 

What this means for patients 

• Dara-VTD is a safe and effective treatment before stem cell transplant. 
• While daratumumab may make stem cell collection a bit more challenging, using the right medications (like CTX and plerixafor) can ensure success. 
• Patients often recover faster after transplant with Dara-VTD. 
• Stem cell transplant remains a key part of treatment and is still possible after Dara-VTD. 

 

Why this study matters 
Dara-VTD does not prevent a successful stem cell transplant. With the right approach to stem cell collection, patients can receive this powerful therapy without compromising their chances of a successful transplant and long-term treatment success. 

 

Reference: 
Della Pepa, R., Palmieri, S., Rocco, S. et al. Impact of Dara-VTD induction therapy on stem cell mobilization outcomes in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation: a multicenter study. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06581-x 

Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies — Annals of Hematology (September 2025) 

 

Background 
Multiple myeloma remains incurable, especially when it develops into relapsed/refractory myeloma (RRMM) after treatment. New immunotherapy treatments are being developed that target a protein found on most myeloma cells called B-Cell Maturation Antigen (BCMA).  

Two main types of BCMA-targeted treatments are: 

• CAR-T cell therapy: A personalized treatment using your own immune cells, modified to attack cancer. 
• BiTEs (bispecific antibodies): Off-the-shelf drugs that help immune cells find and kill myeloma cells. 

 

What is the purpose of the study? 
Researchers reviewed 26 studies involving over 2,200 patients to compare how effective and safe CAR-T therapies are compared to BiTEs in treating RRMM. 

 

Key findings  

• CAR-T therapy had a higher response rate (84%) and deeper remissions (complete response in 55%) than BiTEs (65% response rate, 41% complete response). 
• Dual-target CAR-T therapies (which attack BCMA + another target) had the best outcomes (92% response rate). 
• Both treatments can achieve minimal residual disease (MRD) negativity, which is linked to better long-term survival. 

 

Side effects and risks 

CAR-T therapies had more serious side effects, especially: 

• Cytokine release syndrome (CRS): a common but manageable immune reaction. 
• Blood-related issues: like low white cells (neutropenia) and platelets. 

BiTEs had fewer severe side effects but caused more infections, possibly due to long-term effects on the immune system. 

 

Special considerations 

• BiTEs may be a better option for older adults or those who can’t tolerate intensive treatments. 
• CAR-T therapy is personalized and takes longer to prepare, while BiTEs are ready to use. 
• Patients who have already had BCMA-targeted therapy may not respond as well to another BCMA treatment. 

 

Why this study matters 

• CAR-T therapies provide stronger and deeper responses but come with more side effects and longer preparation time. 
• BiTEs are safer and easier to access, making them a good option for some patients, though they may not work as well as CAR-Ts. 
• These findings help doctors and patients choose the best treatment based on individual health, prior treatments, and personal preferences. 

 

If you have relapsed/refractory multiple myeloma, BCMA-targeted therapies are promising new options. CAR-T might offer better chances of remission but comes with more risks and time delays. BiTEs may be safer and faster to start. Talk to your doctor about which option fits your condition and lifestyle best. 

 

Reference: 
Techaapornkun, P., Rojpalakorn, W., Mejun, N. et al. Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06524-6 

 

Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study — Leukemia (September 2025) 

 

What is the purpose of the study? 
Infections are a serious issue for myeloma patients. Smoldering multiple myeloma (SMM) may still affect the immune system. This study explored whether people with SMM are more likely to get infections, even before developing full-blown myeloma. 

 

How was the study conducted? 

• The research used data from the iStopMM study in Iceland, where over 75,000 people aged 40+ were screened for early signs of myeloma. 
• 188 people diagnosed with SMM were compared to:

           - 188 people with monoclonal gammopathy of undetermined significance (MGUS) — the precursor to myeloma. 

           - 810 healthy individuals with no MGUS nor SMM (healthy controls) 

• The study looked at medical records and prescription data to track infections and antibiotic use. 

 

Key findings 

• People with SMM had more infections than both MGUS and healthy individuals. 

          - They were 36% more likely to get infections than healthy people. 
          - They also had more antibiotic prescriptions, suggesting more bacterial infections or concerns. 

• Even low-risk SMM (not requiring immediate treatment) showed increased infection risk. 
• Compared to MGUS, SMM had a higher infection rate, though the difference was smaller. 

 

What kind of infections were observed? 

• Respiratory infections were the most common across all groups. 
• SMM patients had more frequent infections overall, not necessarily more severe ones. 
• More antibiotics were prescribed to SMM patients, which may reflect increased bacterial infections. 

 

Limitations of the study 

• Most people studied had low-risk SMM, so results may not fully apply to those with high-risk SMM. 
• The study didn't measure infection severity, only whether infections occurred. 
• Some infections may not have been recorded if patients didn’t seek care. 

 

Why these findings matter 

• These findings show that SMM may impair the immune system, even before symptoms appear or treatment begins. 
• Immunoparesis—a condition where healthy antibodies are reduced—seems to partly explain the risk but not completely. 
• This suggests a hidden vulnerability to infections in people with SMM, even those considered low risk. 

 

What does this mean for patients? 

• If you have SMM, especially if you’re newly diagnosed, you may be more prone to infections than you realize. 
• This could affect future decisions about monitoring, vaccination, or possibly early treatment. 
• While current guidelines don’t offer special recommendations for people with SMM, this study suggests doctors should pay closer attention to infection risks in this group. 

 

Conclusion 

• People with SMM have a higher risk of infections, even when considered low-risk and not yet needing treatment. 
• This risk is partly due to reduced immune function and highlights the need for better awareness, monitoring, and possibly preventive care. 
• Future research should explore whether those with frequent infections are at higher risk of progressing to full myeloma, and if early treatment or other measures could help. 

 

Reference: 
Andersen, L.S., Navarro, R.B., Ekberg, S. et al. Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study. Leukemia (2025). https://doi.org/10.1038/s41375-025-02762-9 

 

A discrete choice experiment analysis to understand patient preferences for multiple myeloma treatments — Frontiers in Oncology (September 2025) 

 
 

What is the purpose of the study? 
With many new treatment options becoming available for relapsed/refractory multiple myeloma (RRMM), it’s important to understand what matters most to patients when choosing a therapy. This study asked RRMM patients what treatment features they value most—such as effectiveness, side effects, or how the treatment is given. 

 

How was the study conducted? 

• 149 RRMM patients in the U.S. completed an online survey (Nov 2023 – Mar 2024). 
• They were given hypothetical treatment choices and asked to choose between them. 
• The survey included features like treatment success, survival, and side effects. 

 

Key findings 

• Patients strongly preferred treatments that helped them live longer and delayed disease progression. 

          Most important factors: 
                    - Progression-free survival (PFS) and overall survival (OS) (36.4% importance) 
                    - Overall response rate (ORR) (22.1%) 

• Patients were most concerned about serious side effects like: 

          - Cytokine release syndrome (CRS) (15.2%) 
          - Infections (11.9%) 
          - Milder issues (e.g., taste changes, nail/skin problems, hospitalization time) were less concerning. 

• Patients are willing to make trade-offs. Many would accept a high risk of CRS (up to 72%) for a 29% improvement in treatment response. 

 

What do these key findings mean? 

• Most patients prioritize living longer and better treatment outcomes over concerns about side effects—especially mild ones. 
• However, they still want to be informed about all possible side effects, even minor ones, to make balanced decisions. 

 

Additional insights: 

• Patients' current health and personal experiences heavily influence their choices. 
• Some new side effects (like those from newer drugs targeting GPRC5D) may be underappreciated simply because patients aren’t yet familiar with them. 
• Despite this, survival benefits tend to outweigh worries about these unfamiliar side effects. 
• The study suggests that clear and full communication between doctors and patients is essential for making the best treatment decisions. 

 

What are the limitations of the study? 

• Most participants were White and well-educated, so results may not reflect the views of all patients, especially minorities. 
• Many hadn’t tried newer treatments yet, so their views on related side effects may not be fully informed. 
• Cost, comorbidities, and other real-world factors weren't included but can be important in actual decisions. 

 

Why this study matters 
Patients with RRMM deeply value treatments that offer better outcomes—even if they come with certain risks. But to make the best choices, they need full information and strong communication with their healthcare providers. Including patient preferences in treatment planning can help achieve better, more personalized care. 

 

Reference: 
Faiman B, Le HH, Laurent J, Patel S, Paner-Straseviciute A, Zhang X and Mikhael J (2025) A discrete choice experiment analysis to understand patient preferences for multiple myeloma treatments. Front. Oncol. 15:1628121. doi: 10.3389/fonc.2025.1628121 

 
Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses — JCO Oncology Practice (September 2025) 

 
 

What is the purpose of the study? 
Talquetamab is a treatment approved for patients with relapsed or hard-to-treat multiple myeloma (a type of blood cancer). One known side effect is cytokine release syndrome (CRS)—a reaction caused by immune system activation.  

This study looked at how often CRS happened after each step-up dose of talquetamab in real-world patients. 

 

How was the study conducted? 
Researchers reviewed 50 patients who received step-up doses of talquetamab between September 2023 and November 2024. They analyzed when and how often CRS occurred at each dosing step. 

 

Key findings 

• CRS occurred in 80% of patients overall. 
• CRS was more common after the first (28%) and second (34%) doses. 
• Only 4% had CRS after the fourth dose, and it was very mild (grade 1). 
• The timing of CRS was similar across doses. 
• Previous use of similar immune therapies didn’t increase CRS risk. 

 

Why this study matters 
The fourth dose of talquetamab is well-tolerated and can likely be safely given in an outpatient clinic instead of requiring hospital stay. This could help reduce healthcare costs and make treatment more convenient. 

 

Reference: 
Issam S. Hamadeh et al. Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses. JCO Oncol Pract 0, OP-25-00224 DOI:10.1200/OP-25-00224  

 

Clinical Trials 

 

Elranatamab Fixed Dosing: A Safe, Effective, and Convenient Dosing Approach — Targeted Oncology (August 2025) 

 
 

Background 
Elranatamab (ELREXFIO®) is a new treatment for relapsed/refractory multiple myeloma (RRMM). It helps the immune system target and kill cancer cells. While many drugs are dosed based on a patient’s body weight, this study looked at whether elranatamab works just as well using the same fixed dose for everyone. 

 

What is the purpose of the study? 
To see if body weight affects how well elranatamab works, how safe it is, and how the body processes the drug. 

 

How was the study conducted?  
Researchers studied data from a clinical trial where all patients received the same fixed weekly dose (76 mg) of elranatamab, regardless of weight. They compared how the drug worked in patients grouped by body weight (from lowest to highest). 

 

Key findings 

• The amount of drug in the body was similar across all weight groups. Slight differences in the highest weight group were not clinically important. 
• The treatment worked equally well across all weight groups, with no major differences in response or how long the benefits lasted. 
• Side effects were consistent across all body weights, including the risk of infections and low blood counts. 
• No increase in Cytokine Release Syndrome (CRS) was seen in patients with different body weights. 
• There was no sign that smaller patients were getting too much drug or larger patients too little. 

 

Conclusion 
A fixed dose of elranatamab is safe and effective for patients of all body weights. This simplifies treatment, reduces dosing errors, and improves access—especially in community healthcare settings. 

 

Why this study matters 
Unlike some other similar treatments that require dosing based on body weight, elranatamab can be given at the same dose to everyone, making it easier and more practical to use without compromising safety or effectiveness. 

 

Reference: 
Elmeliegy, M., Soltantabar, P., Hibma, J. et al. Elranatamab Fixed Dosing: A Safe, Effective, and Convenient Dosing Approach. Targ Oncol (2025). https://doi.org/10.1007/s11523-025-01170-4 

 

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

 
Summary 

• Frailty, not just age, plays a major role in how well older adults with multiple myeloma respond to treatment and how long they live. 
• Many clinical trials don’t specifically study frail patients, so there’s limited information on how effective or tolerable newer treatments are for them. 
• The HOVON 143 trial was the first study designed for frail patients using a standard frailty measure (IMWG-FI). 

 

How was the study conducted? 
Patients were treated with a combination of ixazomib, daratumumab, and low-dose dexamethasone, followed by maintenance therapy. 

 

Key findings 

• The average time before the disease worsened was 13.8 months. 
• The average survival was 34.0 months (less than 3 years). 
• Not all frail patients are the same. 
• Some are frail due to age only (e.g. over 80). 
• Others have physical or health impairments that make them more vulnerable. 
• Those with impairments had worse outcomes and higher risk of early death than those who were frail due to age alone. 

 

Why this study matters 
These findings suggest that we need better ways to define and assess frailty, so doctors can identify patients most at risk and tailor treatments accordingly. 

Reference: 
Febe Smits, Kaz Groen, Mark-David Levin, Claudia A.M. Stege, Roel J.W. van Kampen, Ellen van der Spek, Inger S. 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 MB 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; Frail subgroups determine heterogeneous outcomes in older patients with NDMM - long-term follow-up of the HOVON 143 trial. Blood Adv 2025; bloodadvances.2025017394. doi: https://doi.org/10.1182/bloodadvances.2025017394 

 

Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1 — Blood Advances (August 2025) 

 
 

Background 

• Talquetamab is a new treatment for relapsed/refractory multiple myeloma (RRMM), approved for targeting a protein called GPRC5D. 
• It is given by injection under the skin either once a week (QW) or every other week (Q2W). 

 
 

Key findings 

In a study of 339 patients, talquetamab showed: 

• Lower rates of serious infections (grade 3/4) compared to similar treatments. 
• Fewer patients had to stop treatment or died due to infections. 
• Most infections were mild, usually affecting the lungs (like COVID-19). 
• Serious infections were most common in the first 1–2 cycles of treatment. 

Talquetamab helps preserve the immune system: 

• B cells stayed stable or increased during treatment. 
• Immunoglobulin G (IgG), a key antibody, improved over time. 
• Few patients needed IVIG (immune support therapy). 

 

Why this study matters 
Overall, talquetamab appears to be a safer, less immune-suppressing option for patients with RRMM, especially those who have already had multiple other treatments. 

 
Reference: 
Carolina Schinke, Paula Rodriguez-Otero, Niels W.C.J. van de Donk, Brea C. Lipe, Noa Lavi, Leo Rasche, Samir Parekh, Oliver Van Oekelen, Deeksha Vishwamitra, Sheri Skerget, Diana Cortes-Selva, Raluca I. Verona, Brandi W. Hilder, Tara Masterson, Michela Campagna, Sheetal Khedkar, Thomas Renaud, Jaszianne Tolbert, Colleen Kane, Kathleen Gray, Ibrahim Saber, Christoph Heuck, Ajai Chari; Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1. Blood Adv 2025; bloodadvances.2025016613. doi: https://doi.org/10.1182/bloodadvances.2025016613 

 

A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma — Blood (August 2025) 

 

What is the purpose of the study? 
This study looked at the effectiveness and safety of a new drug, modakafusp alfa, in patients with relapsed/refractory multiple myeloma (RRMM). 

 

Key findings 

• Modakafusp alfa is a new type of drug that targets CD38-positive myeloma cells using interferon alfa, an immune-stimulating protein. 
• Two doses were tested: 

           - 120 mg every 4 weeks 
           - 240 mg every 4 weeks 

• Overall response rates (ORR): 

         - 32% of patients responded to the 120 mg dose 
        - 41% of patients responded to the 240 mg dose 

• Responses were better in patients who had not previously received BCMA-targeted therapy (51% response with 240 mg vs 31% in those who had). 
• The drug showed promising activity even in patients who had received multiple prior treatments (median of 6). 

 

Side effects 

• Most common side effects were low blood counts: 

          - Thrombocytopenia (low platelets) and neutropenia (low white blood cells) occurred in most patients, especially at the higher dose. 

• Serious side effects occurred in: 

         - 39% (120 mg group) 
         - 44% (240 mg group) 

• These side effects were generally manageable with supportive care. 
• Importantly, no patients experienced cytokine release syndrome or severe immune-related brain issues, which are concerns with some other immune therapies. 

 

Why was the study discontinued? 

• The drug development was discontinued by the sponsor (the company funding the trial) for strategic reasons, not because of safety or lack of effectiveness. 
• The fast-changing landscape of multiple myeloma treatments and long development timelines contributed to this decision. 

 

What does this mean for patients? 

• Modakafusp alfa showed meaningful results, even in patients who had run out of treatment options. 
• While this specific drug will not continue in development, the results support further research into similar immune-based treatments for RRMM. 
• The study also shows that new approaches—like targeting CD38 and using immune-stimulating agents—hold promise in the fight against myeloma. 

 

Reference: 
Sarah A. Holstein, Shebli Atrash, Hira Mian, Meletios A. Dimopoulos, Fredrik Schjesvold, Rakesh Popat, Nishi Shah, Moshe E. Gatt, Christian B. Gocke, Laurent Frenzel, Cyrille Touzeau, Meral Beksac, Salomon Manier, Hila Magen, Patrick Travis, Omar Nadeem, Kaveri Suryanarayan, Cheryl Li, Shuli Li, Allison Nelson, Dasha Cherepanov, Xavier Parot, Dan T. Vogl; A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma. Blood 2025; 146 (9): 1051–1064. doi: https://doi.org/10.1182/blood.2024027873 

 
Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial — Haematologica (September 2025) 

 

What is the purpose of the study? 
Frail patients with multiple myeloma often have worse outcomes. The IMROZ trial studied whether adding a drug called isatuximab (Isa) to a standard treatment (VRd: bortezomib, lenalidomide, and dexamethasone) could improve results, especially for patients who are not healthy enough for a stem cell transplant. 

 

How was the study conducted? 

• Patients received either Isa-VRd followed by Isa-Rd, or VRd followed by Rd. 
• Frailty was measured using a score that considered health conditions and physical function. 
• About 27% of patients were classified as frail. 
• The study excluded people over 80 years old but not based on frailty alone. 

 

Key results 

• After nearly 5 years of follow-up, Isa-VRd helped both frail and non-frail patients live longer without their disease getting worse (called progression-free survival). 
• Among frail patients, Isa-VRd more than doubled the rate of deep treatment responses (including undetectable cancer levels) compared to VRd alone. 
• Side effects and treatment tolerability were similar between frail and non-frail patients, and between treatment groups. 
• Patients on Isa-VRd stayed on treatment longer than those on VRd, suggesting better disease control. 

 

Comparison to other treatments 

• Similar studies with other drugs (like daratumumab) also showed benefits for frail patients, but Isa-VRd showed higher response rates in this analysis. 
• Isa-VRd appears to be a promising option for frail patients under age 80, with results suggesting both effectiveness and manageable side effects. 

 

Safety and tolerability 

• Frail patients tolerated the quadruplet (4-drug) treatment well. 
• Rates of serious infections, nerve problems, and other side effects were not significantly higher in frail patients. 
• Preventive antibiotics helped lower infection risk. 
• Medication dosing was similar across frail and non-frail groups, showing good tolerability. 

 

Limitations of the study 

• The study did not include patients over 80, so results might not apply to that age group. 
• Frailty was assessed based on existing health records, which might have missed some information. 
• More research is needed on "ultra-frail" patients (those with the poorest health). 

 

Why this study matters 
Isa-VRd is a safe and effective treatment option for frail patients under age 80 who are newly diagnosed with multiple myeloma and not eligible for transplant. This is the first study to show that a 4-drug regimen including isatuximab can benefit frail patients in this setting. 

 

Reference: 
Manier S, Dimopoulos M-A, Leleu XP, Moreau P, Cavo M, Goldschmidt H, Orlowski RZ, Tron M, Tekle C, Brégeault M-F, Shafer AT, Beksac M, Facon T. Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial. Haematologica 2025;110(9):2139-2150; https://doi.org/10.3324/haematol.2024.287200. 

Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study — Haematologica (September 2025) 

 
What is the purpose of the study? 
This study looked at how well two advanced tests—next-generation flow cytometry (NGF) and next-generation sequencing (NGS)—can detect minimal residual disease (MRD) in patients with multiple myeloma after a stem cell transplant and ongoing treatment with lenalidomide. 

Even when tests show no signs of cancer, small amounts of disease can remain. Detecting this early helps doctors better understand a patient’s risk of relapse and make informed treatment decisions. 

 

Key findings 

• 52 patients in Japan who had a stem cell transplant and achieved complete response were followed. 
• MRD was measured in bone marrow at 3 different times: within 1 year after transplant, then at 1 and 2 years. 
• Both tests (NGF and NGS) gave very similar results. 
• Patients who remained MRD-negative for more than 6 months had a much better chance of staying in remission. 
• After 3 years: 

         - 76.5% of patients had no disease progression. 
         - 96.2% were still alive. 

• Patients who stayed MRD-negative had better outcomes than those who became MRD-positive again. 
• In some cases, MRD was missing due to the patchy nature of the disease or technical issues with bone marrow sampling. 
• Peripheral blood tests and more sensitive methods (like mass spectrometry) may improve future MRD detection. 

 

Treatment implications 

• Patients who stay MRD-negative may one day reduce or stop treatment. 
• Those who become MRD-positive again may benefit from early additional treatment. 

 

Side effects 

• Serious side effects from lenalidomide were seen in 16% of patients, mainly infections and low white blood cell counts. 
• No secondary cancers were reported, possibly due to the short follow-up. 

 

What are the limitations of the study? 

• Although the target number of patients was enrolled, only 52 were analyzed, and subgroup analyses had limited statistical power. This makes it harder to draw firm conclusions, especially for high-risk subgroups. 
• 17% of patients were excluded because they received other maintenance treatments (not lenalidomide). This further reduced the number of patients analyzed. 
• Only 17% of patients had PET/CT scans at the start. This might have missed cases with disease outside the bone marrow, leading to false-negative MRD results. 
• Bone marrow samples were collected differently across centers, which may have caused variability in MRD results. 
• Possible dilution with blood or different sample timing may have led to inconsistent detection. 
• Autograft samples (stem cells used for transplant) were only 2 mL, limiting MRD test sensitivity. 
• NGS testing failed in 6% of patients due to poor DNA quality. 
• The follow-up period may have been too short to detect long-term effects like second cancers or very late relapses. 
• The study included patients with a mix of standard- and high-risk genetic features, but only one ultra–high-risk case. 
• This limits conclusions about how well MRD negativity predicts outcomes in the highest-risk patients. 

While the study provides valuable insights into MRD testing in multiple myeloma, larger, longer-term studies are needed to confirm the results and guide treatment decisions based on MRD status. 

 

Why this study matters 

• Regular, sensitive MRD testing is useful for monitoring response and guiding treatment. 
• Staying MRD-negative is linked to excellent long-term outcomes. 
• Larger studies are needed to confirm whether early treatment changes based on MRD status improve survival. 

 

Reference: 
Yoroidaka T, Takamatsu H, Urushihara R, Itagaki M, Yoshihara S, Sato K, Takezako N, Ozaki S, Suzuki K, Kohno K, Muta T, Matsumoto M, Terasaki Y, Yamashita T, Fuchida S- ichi, Sakamoto J, Ishida T, Suzuki K, Murakami H, Durie BG, Shimizu K. Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study. Haematologica 2025;110(9):2160-2170; https://doi.org/10.3324/haematol.2025.287411. 

 
Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study — Targeted Oncology (September 2025) 

 
Background 
Belantamab mafodotin is a type of targeted cancer therapy used to treat relapsed or refractory multiple myeloma (RRMM). It is combined with the drugs pomalidomide and dexamethasone (called BPd therapy). The DREAMM-8 study tested how effective and safe this treatment is. 

 

What is the purpose of the study? 
Researchers wanted to understand how the amount of belantamab mafodotin given in the first cycle of treatment (either 2.5 mg/kg or 1.9 mg/kg) affected: 

• How well the cancer responded to treatment 
• The risk of side effects, especially eye problems 

 

Key findings 

1. Starting with a 2.5 mg/kg dose led to deeper responses (more patients achieved strong treatment effects, like complete remission or no detectable cancer). A lower dose of 1.9 mg/kg resulted in weaker responses. 
2. Even though eye-related side effects (like vision changes) are common with this drug, starting at 2.5 mg/kg did not increase the risk of serious eye problems compared to the lower dose. 
3. Patients with more aggressive disease tend to break down the drug faster, which may lower its effectiveness. Starting at a higher dose helps overcome this and gives the drug time to work before reducing the dose in later cycles. 
4. After the first cycle, the dose is reduced to 1.9 mg/kg every 4 weeks. This approach allows strong early treatment while minimizing long-term side effects. Additional dose changes are made based on each patient's needs. 
5. Eye issues seem to happen because the drug is absorbed into the surface of the eye (not because of how much drug is in the blood). These effects are usually manageable and can be addressed by adjusting the dose if needed. 

 

Why this study matters 
Starting with a 2.5 mg/kg dose of belantamab mafodotin in BPd treatment gives patients a better chance of responding well to therapy, without increasing serious side effects, especially to the eyes. This supports the dosing approach used in the DREAMM-8 study. 

 

Reference: 
Hanafin, P., Ho, Y.L., Papathanasiou, T. et al. Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study. Targ Oncol (2025). https://doi.org/10.1007/s11523-025-01174-0 

 
Phase 1/2 Clinical Trial for RRMM Patients: Cell Centric Initiates Dosing of Inobrodib in Combination with Bispecific Antibodies in Multiple Myeloma 

On Wednesday, September 3, Cell Centric (a clinical-stage biotechnology company developing inobrodib — a first-in-class, oral p300/CBP inhibitor for the treatment of multiple myeloma) announced via a press release “that it has initiated dosing in new cohorts evaluating inobrodib in combination with B-cell maturation antigen (BCMA) directed CD3 T-cell engagers.” 

“The ongoing Phase 1/2 clinical trial for the treatment of patients with relapsed/refractory myeloma has now initiated new dosing cohorts evaluating inobrodib in combination with teclistamab-cqyv and inobrodib in combination with elranatamab-bcmm (NCT0406857). Approximately 40 patients are expected to receive the combination of inobrodib with either bispecific agent. Initial safety evaluation data is expected by the end of 2025. Other treatment regimens are also being assessed as part of this study,” stated Cell Centric further about the clinical trial. 

 
K36 Therapeutics: Clinical Trial Update on KTX-1001 in Multiple Myeloma  

 

On Tuesday, September 16, K36 Therapeutics provided a clinical update on KTX-1001 — “a first-in-class NSD2/MMSET inhibitor, in combination with carfilzomib and dexamethasone. NSD2 (also known as MMSET) is overexpressed in MM patients with the t(4;14) chromosomal translocation, one of the highest-risk genetic subtypes of the disease," as stated in a press release. 

According to K36 Therapeutics, it has also “begun dosing patients in a separate cohort evaluating KTX-1001 in combination with mezigdomide, a novel investigational therapy from Bristol Myers Squibb (BMS) currently completing enrollment in two pivotal late-stage trials.”   

K36 Therapeutics and BMS “have entered into a clinical trial supply agreement under which K36 will sponsor and run the trial to evaluate the novel triplet of KTX-1001 mezigdomide and dexamethasone in patients with relapsed/refractory multiple myeloma,” stated the press release further. 

 
Johnson & Johnson: Updated Results of Phase 2 MajesTEC-5 Trial  

On Friday, September 19, Johnson & Johnson announced via a press release that "an investigational immune-based induction regimen with TECVAYLI® (teclistamab-cqyv) and DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) demonstrated meaningful clinical efficacy in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM)." 

According to the press release, 49 patients received one of three treatment combinations that included TECVAYLI®, DARZALEX FASPRO®, and lenalidomide, with or without bortezomib, using a steroid-sparing approach. 

Results of the Phase 2 MajesTEC-5 trial revealed: 

• 100% of patients responded to treatment after the initial therapy phase. 
• Among 46 patients tested for minimal residual disease (MRD), all showed no detectable cancer after treatment, based on sensitive lab tests. 
• After six treatment cycles, 85.7% (42 out of 49) had a complete response or better and were MRD-negative. 
• 96% of patients successfully completed stem cell collection, with a strong average yield. 

These results suggest high response rates and effective disease clearance in all treatment groups. 

In terms of safety, the treatment was generally well-tolerated. 

• The most common side effects were related to low blood counts. 
• Serious side effects occurred in 53% of patients, and 36.7% had serious infections. 
• Importantly, no patients had to stop treatment because of side effects, and no life-threatening (Grade 5) events were reported. 
• No cases of ICANS (a serious type of brain-related side effect) were seen. 
• Cytokine release syndrome (CRS) occurred in 65% of patients, but all cases were mild or moderate (Grade 1 or 2). 

These results support the overall safety of the treatment approach. 

 

U.S. Food and Drug Administration (FDA) 

 
U.S. Food and Drug Administration (FDA) Approves BILPREVDA® (denosumab-nxxp) 

 
On Tuesday, September 2, the U.S. Food and Drug Administration (FDA) approved BILPREVDA® (denosumab-nxxp) injection 120 mg/1.7 mL, “a RANK ligand (RANKL) inhibitor indicated for multiple myeloma and bone metastasis from solid tumors,” states Organon in a press release. 

“BILPREVDA is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors,” the press release stated further. 

 

U.S. FDA Approves Lenalidomide Capsules Manufactured at Lupin Limited in India  

On Wednesday, September 17, Lupin Limited announced via a press release that the U.S. Food and Drug Administration (FDA) has approved the Abbreviated New Drug Application for Lenalidomide Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg.  

“Lenalidomide Capsules are bioequivalent to Revlimid®* Capsules, 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg, of Bristol-Myers Squibb Company. This product will be manufactured at Lupin’s Pithampur facility in India.”  

“Lenalidomide Capsules are indicated for the treatment of adult patients with multiple myeloma: in combination with dexamethasone; and as maintenance following autologous hematopoietic stem cell transplantation (auto-HSCT,” stated the press release further. 

According to CNBC TV 18 News, the FDA previously issued six observations for the company’s Nagpur injectable facility.  

In response, Lupin Limited stated: “We will address the observations and respond to the U.S. FDA within the stipulated timeframe. We are committed to be compliant with current good manufacturing practices (CGMP) quality standards across all our facilities.” 

(*Safe Harbor Statement: Revlimid® is the registered trademark of Celgene Corporation, a Bristol-Myers Squibb Company.) 

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