July and August 2025: What’s New in Myeloma?
 
 

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, learn more about “a new chapter in relapsed/refractory myeloma;” an up-to-date overview of risk stratification systems on MGUS, smoldering myeloma, and multiple myeloma; practical guidance on the clinical management of belantamab mafodotin related to associated ocular events in myeloma; challenges and strategies in vaccination for myeloma patients; and the inclusion of linvoseltamab as a preferred agent in the newest myeloma practice guidelines of the National Comprehensive Cancer Network (NCCN). Additionally, catch up on some of the latest in myeloma research and clinical trials. 

Editorial 

A new chapter in relapsed or refractory multiple myeloma — The Lancet Haematology (August 2025, Editorial) 

 
Summary 
Even with decades of progressive research, multiple myeloma remains incurable, and most patients eventually relapse. New drugs like proteasome inhibitors, monoclonal antibodies, CAR T-cell therapies, and antibody–drug conjugates have improved outcomes and increased remission rates. However, treatments have become more complex, and options decline with each relapse, especially in resistant cases. There’s a growing need for more personalized and innovative therapies. 

 
Recent research and drug approvals are offering new hope: 

• The BELLINI trial (https://ashpublications.org/blood/article/138/Supplement%201/84/477532/Final-Overall-Survival-Results-from-BELLINI-a) tested venetoclax with other drugs. While it didn’t show a clear survival benefit for all patients, those with a specific genetic marker (t(11;14) or high BCL2 levels) may benefit—highlighting the need for targeted, biomarker-driven treatment. 
• The DREAMM-7 trial (https://www.myeloma.org/videos/dreamm-7-bvd-vs-dvd-relapsed-refractory-multiple-myeloma-phase-3-survival-efficacy-update) showed strong results for belantamab mafodotin (a BCMA-targeting antibody–drug conjugate) combined with bortezomib and dexamethasone (BVd). This combo improved survival compared to a standard treatment and maintained quality of life, even for those with vision-related side effects. 
• Regulatory bodies are currently reviewing belantamab mafodotin again, after it was previously withdrawn. The UK has already reapproved it based on new data, while the FDA's Oncologic Drugs Advisory Committee (ODAC) recently voted against it, with a final decision pending in October 2025 (https://us.gsk.com/en-us/media/press-releases/gsk-announces-extension-of-us-food-and-drug-administration-review-period-for-blenrep-belantamab-mafodotin-blmf-in-relapsedrefractory-multiple-myeloma/). 
• The FDA and EMA have also approved a new therapy, linvoseltamab (Lynozyfic™), for patients who have had three or more prior treatments. In early trials, 70% of patients responded, and nearly half had a complete response. Side effects like cytokine release syndrome (CRS) and neurotoxicity were mostly mild and manageable. 

These advancements are changing the way multiple myeloma is treated. However, with so many choices, it’s harder to know which treatment to use and when. Experts believe it’s time to use genetic and molecular testing—as done in other cancers—to guide personalized treatment plans for each patient. 

Reference: 
The Lancet Haematology, A new chapter in relapsed or refractory multiple myeloma, The Lancet Haematology, Volume 12, Issue 8, 2025, Page e561, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00205-4 (https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00205-4/fulltext).  

Guidelines, Recommendations, and Strategies  

Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma — Hemasphere (July 2025) 

What is the purpose of this review? 
This article reviews the growing evidence supporting the use of a powerful drug combination: carfilzomib, lenalidomide, and dexamethasone (KRd), for treating patients with newly diagnosed multiple myeloma (NDMM), especially when combined with anti-CD38 antibodies like daratumumab (D) or isatuximab (Isa). 

What are the key points? 

• KRd is a strong treatment option for NDMM, especially in patients who are eligible for a stem cell transplant. 
• Adding anti-CD38 antibodies (Isa or D) to KRd forms a quadruplet regimen (Isa-KRd or D-KRd), which shows deep and lasting responses, even in high-risk patients. 
• Studies report high rates of minimal residual disease negativity (MRD−), meaning no detectable cancer cells remain using sensitive tests, which is linked to longer remissions. 
• For example: Isa-KRd led to MRD− rates up to 77% in Phase 3 trials; D-KRd achieved MRD− in 81% of patients at any time in one study. 
• These combinations may work especially well in: Patients at higher genetic risk; Those at higher risk for nerve damage (where KRd may be better tolerated than other regimens) 

What’s the current recommendation? 

• In the U.S., the NCCN now recommends Isa-KRd and D-KRd as preferred frontline treatments for NDMM. 
• In Europe, they are not yet widely approved, but that may change as more evidence becomes available. 

Why this review matters 
KRd combined with Isa or D is an effective, well-studied option for newly diagnosed multiple myeloma—offering deep responses and hope for longer remission, especially in high-risk patients. These combinations are likely to become more common in treatment as guidelines continue to evolve. 

Reference: 
Landgren, O., Biran, N., O'Donnell, E.K., Mikhael, J., Weisel, K.C., Broijl, A., Usmani, S.Z., Moreau, P., Gay, F.M., Mina, R., Rodríguez-Otero, P., Jakubowiak, A.J. and Derman, B.A. (2025), Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma. HemaSphere, 9: e70178. https://doi.org/10.1002/hem3.70178 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70178)

Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders — Leukemia (July 2025, Review) 

 
What is the purpose of this review? 
The purpose of the review is to provide an up-to-date overview of risk stratification systems across clonal plasma cell disorders to guide clinical decision-making and support personalized treatment strategies. 

Understanding a patient’s risk level is key to choosing the right treatment for plasma cell disorders—helping doctors give more intensive care to those who need it most, and lighter, safer options for those likely to do well. This review explains the best current methods for assessing risk and guiding personalized care. 

How doctors use risk stratification for MGUS, smoldering myeloma, and multiple myeloma 
Plasma cell disorders include a group of related diseases such as monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). 

These conditions vary widely in how they behave and progress, and doctors use risk stratification systems to estimate how serious the disease is and guide treatment decisions. 

Monoclonal Gammopathy of Undetermined Significance (MGUS) 
For MGUS, risk factors for progression include: 

• Abnormal blood light chain ratios 
• M-protein level ≥1.5 g/dL 
• A non-IgG type of protein 

Patients with more of these factors are at higher risk of developing serious disease. Low-risk patients often don’t need frequent testing or invasive procedures. 

Smoldering Multiple Myeloma  
For smoldering myeloma, one commonly used system is the “20/2/20” model, based on: 

• Bone marrow plasma cells >20% 
• M-protein >2 g/dL 
• Light chain ratio >20 

Patients with 2 or more of these features are considered high-risk, with up to 44–63% chance of progression in 2 years. These patients may benefit from early treatment or joining clinical trials. 

Multiple Myeloma  
For multiple myeloma, several systems have been used to estimate risk: 

• ISS and R-ISS: Use blood test results (albumin, beta-2 microglobulin, LDH). 
• Cytogenetic testing (FISH): Looks for specific changes in chromosomes (e.g., del(17p), t(4;14), 1q21 gain). 
• New 2024 System (IMS/IMWG): Classifies high-risk myeloma based on key genetic changes and abnormal blood markers. This newer model is more accurate and identifies about 20% of patients as high-risk. 

Doctors are also studying other risk factors like circulating tumor cells, genetic mutations, and immune system strength to better personalize care. 

Why risk stratification matters 
Risk stratification helps doctors: 

• Identify which patients need urgent or intensive treatment 
• Avoid unnecessary treatment in low-risk patients 
• Personalize care to improve outcomes and reduce side effects 

As research advances, risk models are becoming more precise, incorporating genetic, tumor, and immune system factors. This is helping guide the shift toward personalized and risk-adapted treatment in plasma cell disorders. 

What is the takeaway for patients?  
If you’ve been diagnosed with a plasma cell disorder, your doctor will use risk assessment tools—mostly based on blood tests, bone marrow results, and genetic testing—to determine how likely your condition is to progress. This helps decide how often you need monitoring and whether treatment should begin. 

Understanding your risk can empower you to make informed decisions and work with your care team to find the best strategy for your situation. 

Reference: 
Zanwar, S., Rajkumar, S.V. Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders. Leukemia (2025). https://doi.org/10.1038/s41375-025-02654-y (https://www.nature.com/articles/s41375-025-02654-y) 

 
Vaccination in Multiple Myeloma: Challenges and Strategies — European Journal of Haematology (July 2025, Review) 

 
Summary 
People with multiple myeloma have weakened immune systems due to both the disease and its treatments, which makes them more vulnerable to infections. Vaccines can help prevent these infections, but responses to vaccines are often weaker in myeloma patients. 

Key Points 

• Vaccines for flu, pneumonia, and COVID-19 are recommended and can help lower the risk of serious infections, even if the immune response is not as strong as in healthy individuals. 
• Some treatments—especially anti-CD38 and BCMA-targeted therapies—can reduce vaccine effectiveness, making booster shots or antibody treatments helpful in some cases. 
• Shingles, hepatitis B, and Haemophilus influenzae vaccines are also important, especially after stem cell transplant. 
• Doctors may use immune tests to check how well your body can respond to vaccines and to help plan your vaccine schedule. 
• Timing and type of vaccine matter. For example, using two types of pneumonia vaccines in a specific order can reduce lung infections. 
• Research continues on stronger or next-generation vaccines to better protect people with myeloma. 

Why this review matters 
Vaccines are an essential part of staying healthy with myeloma. Even if the response isn't perfect, they help reduce infections and hospital visits. A personalized vaccination plan, based on your treatment and immune health, gives the best protection. 

Reference: 
E. A. Martino, E. Vigna, A. Bruzzese, et al., “Vaccination in Multiple Myeloma: Challenges and Strategies,” European Journal of Haematology (2025): 1–10, https://doi.org/10.1111/ejh.70013. (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70013) 

 
Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events — American Journal of Hematology (July 2025, Critical Review) 

Summary 
Belantamab mafodotin (belamaf) is an antibody-drug conjugate that targets and kills myeloma cells. However, it can cause eye-related side effects, such as dry eyes, light sensitivity, or temporary changes in vision. These issues are usually reversible once treatment is paused or adjusted. 

Because this is a newer drug, doctors need clear guidance on how to manage these eye problems. A group of experts developed practical recommendations based on clinical trial data, so that treatment with belamaf can be given safely and effectively, while protecting patients’ vision. 

What is the purpose of the review? 
Belantamab mafodotin (belamaf) is an effective treatment for relapsed or hard-to-treat multiple myeloma, but it can cause common eye-related side effects.  

This review provides expert recommendations on how doctors can safely recognize, monitor, and manage eye-related side effects caused by the drug (mostly through adjusting the dose, using eye drops, and regular eye check-up) without reducing the treatment’s effectiveness. 

Because belamaf can cause eye issues (like blurry vision or dry eyes), the study offers practical advice on: 

• When patients should have eye exams 
• How to adjust treatment doses if vision changes happen 
• Ways to protect vision without reducing the cancer treatment’s effectiveness 

The goal is to help doctors use belamaf safely and effectively, while keeping patients’ vision and quality of life in mind. 

What are the key points for patients? 

• Baseline eye check: An eye exam is recommended before starting belamaf. If a patient’s disease is worsening, treatment can begin while waiting for the eye exam. 
• Cataracts and other eye conditions: Common in older patients and those who’ve had past treatments. These do not prevent you from receiving belamaf. 
• Monitoring during treatment: Eye checks should be done before doses 2, 3, and 4. After that, doctors may use a short questionnaire to check your symptoms and decide if you need to see an eye doctor again. 
• Dose adjustments: If vision changes occur, doctors may pause or reduce the dose. This does not reduce how well the treatment works. 
• Common eye symptoms: Blurred vision, dry eyes, feeling like something is in your eye, or trouble with bright lights. Most symptoms get better within 8–12 weeks if the drug is paused. 
• Vision impact: Most patients don’t stop daily activities like reading or driving, and eye symptoms generally don’t affect overall quality of life long-term. 
• Communication: It’s important to tell your care team about any eye problems right away. Doctors and eye specialists work together to manage your care. 
• Patient education: Patients should receive clear information about possible eye side effects and what to expect. Educational tools are available to support understanding. 

Why this review matters 
Eye side effects from belamaf can be managed effectively without reducing its benefit in treating multiple myeloma. With close monitoring, good communication, and appropriate dose adjustments, patients can continue treatment safely and maintain quality of life. 

Reference: 
E. Terpos, S. Trudel, M.-V. Mateos, et al., “Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events,” American Journal of Hematology (2025): 1–12, https://doi.org/10.1002/ajh.70015. (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70015) 

Lynozyfic™ (linvoseltamab-gcpt) included as a ‘preferred agent’ in the newest practice guidelines for multiple myeloma (July 2025, News Article) 

According to a July 31 news article from AJMC, (https://www.ajmc.com/view/linvoseltamab-added-as-preferred-agent-in-newest-mm-practice-guidelines) the National Comprehensive Cancer Network (NCCN) recently added Lynozyfic™ (linvoseltamab-gcpt) as “a preferred agent in the newest multiple myeloma practice guidelines.”  

On July 2, the U.S. Food and Drug Administration granted accelerated approval for Lynozyfic™ (linvoseltamab-gcpt) “to treat adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti‑CD38 monoclonal antibody. Lynozyfic was granted accelerated approval based on response rate and durability of response in the LINKER-MM1 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial,” stated Regeneron in a press release (https://investor.regeneron.com/news-releases/news-release-details/lynozyfictm-linvoseltamab-gcpt-receives-fda-accelerated-approval). 

Lynozyfic is now a preferred treatment for RRMM patients, after 4 or more prior therapies. It joins 3 other similar "bispecific antibody" treatments already recommended. 

Key points 

• FDA approval: Linvoseltamab was approved in July 2025 after a clinical trial (LINKER-MM1) showed it helped 70% of patients respond to treatment, and 45% achieved a complete response. 
• How it works: It's a bispecific antibody that helps the immune system target and kill myeloma cells by connecting immune T cells to the cancer. 
• New guidelines: The National Comprehensive Cancer Network (NCCN) added linvoseltamab as a preferred option for patients who’ve already tried other treatments (including a CD38 antibody, proteasome inhibitor, and immunomodulatory drug). 

Additional guideline updates 

1. More accurate response tracking: New definitions for how doctors measure response to treatment, including minimal residual disease (MRD) testing and relapse. 

2. Special populations section: Includes guidance for: 

• Older or frail adults 
• Black/African American patients, who may have different myeloma biology and outcomes 

3. Expanded topics covered: 

• Diagnosis and treatment of: 

                - Smoldering myeloma (early, symptom-free form) 
                - Myeloma with brain/spinal cord involvement 

• Updates to follow-up care, supportive care, and imaging guidelines 

Why these guideline updates matter 

• Linvoseltamab adds another effective option for patients who have run out of others. 
• Broader, updated guidelines help ensure more personalized, equitable, and evidence-based care for all people living with multiple myeloma. 

Reference: 
AJMC, “Linvoseltamab Added as a Preferred Agent in Newest MM Practice Guidelines, (https://www.ajmc.com/view/linvoseltamab-added-as-preferred-agent-in-newest-mm-practice-guidelines)” July 31, 2025. 

 
Research 

Whole body MRI by MY-RADS for imaging response assessment in multiple myeloma — Blood Cancer Journal (July 2025) 

Background 
In multiple myeloma, minimal residual disease (MRD) testing is important to check if cancer remains after treatment. However, MRD tests that use bone marrow samples can overlook cancer due to uneven distribution of disease in the body. 

Findings from the iTIMM trial 
The iTIMM clinical trial tested the use of whole-body MRI (WB-MRI), a radiation-free imaging method, to detect remaining cancer after treatment and stem cell transplant. 

• 70 patients with newly diagnosed or relapsed myeloma had WB-MRI scans before treatment and again 100 days after stem cell transplant. 
• Patients with no visible cancer on MRI (RAC1) had much better outcomes than those with signs of remaining disease (RAC2 or higher): 

            - Progression-free survival (PFS): 42 months vs. 24 months 
            - Overall survival (OS): Not reached vs. 47 months 

Patients with no signs of disease on MRI lived longer without their cancer returning—and lived longer overall. 

Why these results matter 

• WB-MRI adds valuable information beyond bone marrow MRD and blood tests. 
• It can detect disease even when other tests show no cancer. 
• The imaging technique (using MY-RADS criteria) is standardized, non-invasive, and does not use radiation. 

Advanced imaging techniques 
Modern MRI tools can also: 

• Measure how active the cancer is (using ADC and fat fraction maps). 
• Distinguish between active disease and scar tissue or benign lesions. 
• Help predict how well a patient will respond to treatment. 

Strengths and limitations of the study 

• Strengths: Prospective design, real-world setting, and use of advanced imaging and MRD testing. 
• Limitations: Conducted at a single center with one MRI machine type; fewer patients received anti-CD38 therapies (now more common). 

Despite these, the results strongly support using WB-MRI in routine care. 

Why this study matters 
This study supports whole-body MRI as a powerful tool to detect remaining cancer in myeloma patients and predict outcomes after treatment. It may soon become a new standard for monitoring multiple myeloma alongside bone marrow and blood-based tests. 

Reference:  
Messiou, C., Porta, N., Koh, DM. et al. Whole body MRI by MY-RADS for imaging response assessment in multiple myeloma. Blood Cancer J. 15, 122 (2025). https://doi.org/10.1038/s41408-025-01327-4  (https://www.nature.com/articles/s41408-025-01327-4)

 
Quantifying Preferences for CAR-T Compared to Standard of Care as a First-Line Treatment Among Patients With Multiple Myeloma — Cancer Medicine (July 2025) 

Background 
CAR-T cell therapy is currently used for relapsed/refractory multiple myeloma but is now being studied as a first-line treatment. Unlike long-term maintenance therapy (which can be burdensome), CAR-T may offer longer periods without relapse and fewer daily treatment disruptions—but it also comes with potential short-term serious risks. 

What is the purpose of the study? 
Researchers asked myeloma patients to choose between different hypothetical treatment options. The goal was to understand how patients weigh: 

• Longer time without relapse 
• Fewer limits on daily life 
• Risk of serious side effects, like hospitalization or treatment-related death 

What are the key findings? 

• Most patients (65%) were willing to accept higher short-term risks in exchange for longer relapse-free time and more freedom from daily treatment limitations. 
• On average, patients valued 2 extra years without relapse and no activity limitations more than avoiding a 20% risk of severe side effects. 
• A smaller group (28%) was less willing to accept treatment-related death, even if it meant longer relapse-free time. 
• A few patients (7%) gave inconsistent or unclear answers. 

For example, many were willing to accept up to an 8% risk of treatment-related death for two more years of relapse-free life with minimal disruption. 

What were the patients’ responses? 

• Younger and college-educated patients were more likely to trade short-term risks for long-term benefits. 
• Older patients and those without a college degree were more likely to avoid any risk of treatment-related death. 

What to keep in mind 

• Patients have different preferences. Not everyone is willing to accept the same level of risk for a potential benefit. 
• These findings highlight the importance of shared decision-making between patients and doctors. Each patient’s values and concerns should guide treatment choices. 

What were the limitations of the study? 

• These were hypothetical treatment scenarios, and real-life decisions may differ. 
• The study didn't cover all possible side effects or treatment features. 
• Participants were mostly white and well-educated, which may limit how broadly the results apply. 

Why this study matters 
Most patients with multiple myeloma are willing to accept some serious short-term risks—like hospitalization or even a small risk of death—for a longer time without relapse and fewer daily treatment burdens. 
 
This underscores the need for open, personalized conversations about treatment goals, side effect risks, and what matters most to each patient—especially as new therapies like CAR-T become available earlier in treatment. 

Reference: 
J. Sutphin, T. W. LeBlanc, E. Janssen, et al., “Quantifying Preferences for CAR-T Compared to Standard of Care as a First-Line Treatment Among Patients With Multiple Myeloma,” Cancer Medicine 14, no. 14 (2025): e71072, https://doi.org/10.1002/cam4.71072.  (https://onlinelibrary.wiley.com/doi/10.1002/cam4.71072)

Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement — Blood Cancer Journal (July 2025) 

What is the purpose of the study? 
This study looked at 80 patients with extramedullary myeloma (EMD) treated with either CAR T-cell therapies (cilta-cel and ide-cel) or bispecific antibodies (bsABs) (teclistamab and talquetamab) at three German hospitals. 

What are the key findings? 

• Better responses with CAR T-cell therapy: 

                - Response rates: 100% with cilta-cel and 82% with ide-cel, compared to 36% (teclistamab) and 29% (talquetamab) with bsABs. 
                - Complete disappearance of EMD: Higher with CAR T-cells (41–50%) than with bsABs (14–16%). 
                - Progression-free survival (PFS): Patients stayed in remission longer with CAR T-cell therapy. 

• Debulking therapy (used before CAR T-cell treatment to reduce tumor size) helped improve outcomes and extend remission. 
• Location matters: EMD in soft tissue or organs responded worse than other EMD areas, regardless of treatment. 
• CAR T-cells may be more powerful because they expand in the body after infusion and are less affected by certain factors (like low T-cell numbers or proteins in the blood) that can limit bsABs. 

What these findings mean 

• CAR T-cell therapy may be more effective than bsABs for treating EMD, especially if patients receive debulking treatment beforehand. 
• However, CAR T-cell therapy is not a cure, and EMD still predicts a poorer outcome overall. 
• Both types of treatment are important, and patients may need multiple therapies over time. 
• More research is needed, especially on the best ways to prepare patients for CAR T-cell therapy and to track responses with imaging. 

Why this study matters 
For patients with EMD, CAR T-cell therapies offer hope, with better response rates and longer remissions compared to bispecific antibodies. Still, EMD remains challenging, and treatment plans should be individualized, often including debulking before CAR T-cell therapy and ongoing monitoring with imaging. 

Reference: 
Steinhardt, M.J., Schaefers, C., Leypoldt, L.B. et al. Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement. Blood Cancer J. 15, 126 (2025). https://doi.org/10.1038/s41408-025-01330-9 (https://www.nature.com/articles/s41408-025-01330-9) 

 
Extramedullary myeloma is genomically complex and characterized by near-universal MAPK pathway alterations — Blood Advances (July 2025) 

What is the purpose of the study? 
This study looks at extramedullary disease (EMD) in multiple myeloma — a form of the disease where cancer spreads outside the bone marrow. EMD is harder to treat and linked to worse outcomes. Researchers wanted to better understand the genetic changes that drive EMD to find possible new treatment options. 

What are the key takeaways? 

• EMD has unique and more complex genetics than typical myeloma. 
• Almost all EMD tumors have mutations in the MAPK pathway (involved in cell growth and survival). 
• EMD tumors show: 

           - A higher number of mutations (called tumor mutational burden or TMB) 
           - Frequent gains in chromosome 1q, linked to aggressive disease 
           - Common changes in genes like NRAS, KRAS, BRAF, MAX, and CDKN2C 
           - Some involvement of genes linked to cell movement and chromatin regulation (ARID1A, EP300, ROBO1/2) 

Limitations of the study 

• The study included a small number of patients (18). 
• More research is needed to confirm these findings and explore new treatments. 

Why this study matters 

• Current treatments often don't work well for EMD, so new approaches are needed. 
• The high number of MAPK pathway mutations could offer a target for future therapies (like MEK inhibitors). 
• Some of the identified genes may help explain why myeloma spreads outside the bone marrow. 
• The higher mutation load might suggest that immune therapies (like checkpoint inhibitors) could be helpful—though this still needs more research. 

Extramedullary multiple myeloma is genetically more complex and often involves mutations in the MAPK pathway, offering possible new directions for treatment. Researchers believe targeted and immune-based therapies may hold promise for the future. 

Reference: 
Saurabh Zanwar, Joseph Novak, Wilson Gonsalves, Michael Howe, Esteban Braggio, S. Vincent Rajkumar, Moritz Binder, Dragan Jevremovic, Surendra Dasari, Shaji Kumar; Extramedullary myeloma is genomically complex and characterized by near-universal MAPK pathway alterations. Blood Adv 2025; 9 (15): 3979–3987. doi: https://doi.org/10.1182/bloodadvances.2025016619  (https://ashpublications.org/bloodadvances/article/9/15/3979/537300/Extramedullary-myeloma-is-genomically-complex-and)

Global, regional, and national burden of multiple myeloma, 1990 to 2021 and predictions to 2035: an analysis of the Global Burden of Disease Study 2021 — Frontiers of Medicine (July 2025) 

What is the purpose of the study? 
This study provides the most up-to-date overview of the global burden of multiple myeloma, based on data from 1990 to 2021 and future projections up to 2035. 

What are the key findings? 

• The number of new cases, deaths, and overall disease burden from myeloma has increased steadily since 1990. 
• In 2021, there were about 148,755 new myeloma cases worldwide. 
• Rates are rising: Global myeloma rates (new cases, deaths, and disability) have increased from 1990 to 2021 and are expected to keep rising through 2035. 
• Higher in wealthier regions: Countries with higher income and better healthcare (high SDI regions) have higher myeloma rates. This may be due to better diagnosis but also poor management of risk factors and treatment gaps. Poorer regions may underreport MM due to late diagnosis and limited healthcare access. 
• Age and gender differences: Myeloma mainly affects people over 50, with rates rising steadily with age. Men generally have higher rates than women, though in some regions, like parts of Africa and Oceania, women are more affected—possibly due to social and healthcare differences. 
• Obesity as a risk factor: 

          - High body mass index (BMI) is a key risk factor for myeloma, responsible for about 8% of myeloma-related disability worldwide in 2021. 
          - The impact is highest in regions like North Africa and the Middle East. 
          - Obesity increases myeloma risk through inflammation and changes in fat cells that support cancer growth. 

• Geographic highlights: 

          - In 2021, Monaco, the Bahamas, and New Zealand had the highest myeloma rates. 
          - Some countries, like Mali, reported almost no cases, possibly due to underreporting. 

Future predictions (2021–2035) 

• Myeloma cases, deaths, and disability are expected to continue rising, especially due to aging populations. 
• Men and older adults will likely remain the most affected groups. 
• Healthcare systems must prepare for more cases by improving early detection, diagnosis, treatment, and care—especially for the elderly. 

What can be done? 

• Improve screening and early diagnosis, especially for older adults. 
• Focus on preventing obesity through healthier lifestyle programs. 
• Ensure better access to treatment, especially in lower-income regions. 
• Customize public health strategies based on each region’s needs and resources. 

Limitations 

• The study relied on existing global data, which may not fully represent every region. 
• Only high body-mass index was analyzed as a risk factor due to limited data on others. 

Why this study matters 
Multiple myeloma is a growing global health issue. With aging populations and rising obesity rates, the burden is expected to increase. Countries need to act now by focusing on prevention, early diagnosis, and equal access to treatment to manage and reduce the impact of this disease. 

Reference: 
Miao X, Wang Z, Wang H, Zeng X, Wang J, Luo B, Yang Y, Yang J, Zhao L. Global, regional, and national burden of multiple myeloma, 1990 to 2021 and predictions to 2035: an analysis of the Global Burden of Disease Study 2021. Front Med (Lausanne). 2025 Jul 31;12:1609692. doi: 10.3389/fmed.2025.1609692.  (https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1609692/full)

The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients — Haematologica (July 2025) 

What is the purpose of the study?  
This study investigates how age affects survival rates and excess mortality in newly diagnosed multiple myeloma patients undergoing autologous hematopoietic cell transplantation (auto-HCT). ​ 

• The study analyzed data from 61,797 patients transplanted between 2013 and 2017, with 60.6% from Europe and 26.2% from the U.S. ​ 
• Median age at auto-HCT was 60.8 years, with 2.0% aged 18–39, 68.9% aged 40–64, 21.8% aged 65–69, 6.5% aged 70–74, and 0.8% aged ≥75. ​ 
• The median age varied by region, with the lowest in the Eastern Mediterranean Region (53.6 years) and highest in Ottawa (62.2 years). ​ 

What are the key findings? 

• Younger patients (18–39 years) had a higher percentage of ISS stage I disease (43.9%) compared to older groups. ​ 
• The percentage of patients with high-risk HCT-specific comorbidity index (HCT-CI) scores increased with age, from 14.4% in the youngest cohort to 49.6% in the oldest. ​ 
• Melphalan 200 mg/m² was the most commonly used conditioning regimen, but older patients were more likely to receive melphalan 140 mg/m². ​ 
• Three-year overall survival (OS) probabilities decreased with age: 85.9% (18–39 years) to 74.8% (≥75 years). 
• Excess mortality rates at three years were similar across age groups, ranging from 13.1% to 15.0%. ​ 
• Older age was a significant risk factor for OS, progression-free survival (PFS), and non-relapse mortality (NRM), but not for excess mortality or relapse risk. ​ 

Limitations of the study 
The study has notable limitations affecting data interpretation and analysis. ​ 

• Variability in reporting practices and data collection across registries leads to missing information. ​ 
• Causes of death and detailed comorbidities were not reported, limiting further analysis. ​ 
• Maintenance therapy data was insufficient for inclusion in the analysis, although 84%-90% of patients received it. ​ 
• The increase in maintenance therapy uptake from 30% in 2013 to approximately 80% in 2017 may explain improved outcomes over time. ​  

Why this study matters 

• The study suggests that age alone should not preclude the use of auto-HCT in multiple myeloma patients. ​ 
• Advances in supportive care have improved outcomes for older patients, leading to increased auto-HCT rates. ​ 
• The findings support the need for individualized treatment approaches based on patient characteristics rather than age alone. 
• Future studies should explore the impact of novel therapies on outcomes in the context of auto-HCT. ​ 

Reference: 
Mizuno S, Gras L, Baaij LG, Koster L, D’Souza A, Hari PN, Estrada-Merly N, Saber W, Cowan AJ, Iida M, Okamoto S, Takamatsu H, Kawamura K, Kodera Y, Hamad N, Ko B-S, Liam C, Ho KW, Goh AS, Keat TS, Elhaddad AM, Bazarbachi A, Chaudhry BQUN, Alfar R, Bekadja MA, Benakli M, Ortiz CAF, Riva E, Verburgh E, Galeano S, Bass F, Mian H, McCurdy A, Wang FR, Neumann D, Koh MBC, Snowden JA, Schönland S, McLornan DP, Hayden PJ, Balari AMS, Greinix HT, Aljurf M, Atsuta Y, Rondelli D, Niederwieser DW, Garderet L. The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients. Haematologica; https://doi.org/10.3324/haematol.2025.288041 (https://haematologica.org/article/view/12198) [Early view]. 

Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma — Blood Cancer Journal (August 2025) 

What is the purpose of the study? 
BCMA-directed bispecific antibodies (BsAbs) are a newer class of treatments showing strong promise in patients with relapsed or refractory multiple myeloma — especially those who have already tried several other treatments. These drugs help the immune system directly attack cancer cells but can come with side effects. 

The purpose of this study is to evaluate and compare the safety and side effect profiles of different bispecific antibodies used to treat relapsed or refractory multiple myeloma, to help guide personalized treatment decisions. 

What are the key findings of the study? 

• This analysis combined results from 22 clinical trials involving 2,374 patients with MM. 
• BsAbs were grouped into two types: BCMA-targeting BsAbs (like teclistamab, elranatamab); and GPRC5D/FcRH5-targeting BsAbs (like talquetamab) 
• Some patients also received combination therapies (e.g., Talquetamab + Daratumumab). 
• BsAbs were effective, with good response rates across both drug groups. 
• BCMA BsAbs showed slightly higher response variability, suggesting they may be more potent in some patients. 

What side effects were observed? 

• Low blood counts (cytopenias): 

          - Neutropenia (low white blood cells): 40% (35% severe) 
          - Anemia (low red blood cells): 39% (24% severe) 
          - Thrombocytopenia (low platelets): 21% (13% severe) 

• Infections: 

          - Occurred in nearly 46% of patients overall. 
         - More common and severe with BCMA BsAbs, especially when used long-term. 

• Cytokine Release Syndrome (CRS): 

          - A common reaction in up to 65% of patients. 
          - Generally mild, but severe in 1.5% of cases. 
          - More frequent with GPRC5D/FcRH5 BsAbs. 

• Neurotoxicity (ICANS): 

         - Less common (about 4%), but still significant. 
         - More likely with talquetamab. 

• Skin and Taste Side Effects (with talquetamab): Rash, nail changes, and altered taste were common but usually mild. 

How are side effects managed? 

• Infections: Preventative antibiotics, antivirals, and IVIG (immune boosters) may be used. 
• Low blood counts: Growth factors (like G-CSF), iron, and other supportive treatments help boost blood counts. 
• CRS:Treated with tocilizumab and/or steroids. Monitoring is critical, especially after the first dose. 
• Neurotoxicity: Managed with steroids. In severe cases, an additional drug called anakinra may be added. 
• Taste changes: Mouth rinses and supplements may help, although evidence is limited. 

Clinical takeaways 

• Both types of BsAbs are effective, but have different side effect patterns: 

          - BCMA BsAbs: Higher risk of blood count problems and infections. 
          - GPRC5D/FcRH5 BsAbs: Higher risk of CRS and taste-related issues. 

• Personalized treatment choices should consider patient history, current health, and ability to manage side effects. 
• Preventive care (e.g., infection prophylaxis, close monitoring) is crucial for safe and effective use. 

Limitations of the study 

• The analysis used summary-level data (not individual patient records), limiting the ability to fully adjust for other risk factors. 
• Some side effects may be underreported or missing from certain studies. 
• More research is needed using detailed, patient-level data to improve treatment decisions. 

Why this study matters 
BsAbs offer powerful new treatment options for patients with relapsed or refractory multiple myeloma. Although they come with unique side effects, most are manageable with close monitoring and supportive care. Choosing the right BsAb depends on the individual patient’s condition, side effect risks, and prior treatments. Ongoing research will continue to refine how these promising therapies are used. 

Reference: 
Golmohammadi, M., Raza, S., Albayyadhi, M. et al. Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma. Blood Cancer J. 15, 130 (2025). https://doi.org/10.1038/s41408-025-01334-5 (https://www.nature.com/articles/s41408-025-01334-5) 

 
Outcomes in frail patients receiving BCMA-directed bispecific antibodies for relapsed/refractory multiple myeloma — Blood Advances (August 2025) 

What is the purpose of the study? 
Patients with relapsed or refractory multiple myeloma (RRMM) often have other health problems and lower physical function, making them seem "frail." These patients are often not included in clinical trials and may be overlooked for newer treatments.

This study looked at 102 patients (ages 40–88) who received BCMA-directed bispecific antibodies (BsAbs). Frailty was based on age, performance status (how physically active), and number of other medical conditions. Patients were either classified as frail (score ≥2) or non-frail (score 0–1). 

What are the key findings of the study? 

• About 40% of the patients were considered frail. 
• Frail patients were more likely to be over age 70 and have other health conditions. 
• In this study, both frail and non-frail patients with relapsed or refractory multiple myeloma responded well to bispecific antibody (BsAb) treatment.  
• Among frail patients, 80% had a positive response to therapy, while 73% of non-frail patients also responded well.  
• When it came to progression-free survival (PFS), there was no significant difference between the two groups.  
• Similarly, overall survival was comparable, with frail patients living a median of 37 months compared to 25 months for non-frail patients.  
• Importantly, the rates of serious side effects were similar in both groups, showing that BsAbs were well-tolerated regardless of frailty status. 
• BsAbs work well and are safe in older and frail patients with RRMM. 
• Age, physical limitations, and other health conditions did not lead to worse outcomes with BsAb treatment.  

Why this study matters 

• Frail and older patients did just as well as younger or healthier patients when treated with BsAbs. 
• Age or frailty should not be a reason to deny treatment or exclude patients from clinical trials. 
• BsAbs can be used safely with the right monitoring and support. 
• Doctors should use practical tools to assess frailty and not rely only on age or appearance. 

If you’re an older adult or have other health conditions, you may still benefit from newer treatments like BsAbs for multiple myeloma. Don’t assume you're "too frail" for effective therapy—talk with your care team about your options. 

Reference: 
Benjamin Adegbite, Carlyn Rose Tan, Tala Shekarkhand, Ross S. Firestone, Eric M. Jurgens, Kevin Miller, Alexander M. Lesokhin, Gunjan L. Shah, Neha Korde, Sridevi Rajeeve, Heather J. Landau, Michael Scordo, Hani Hassoun, Kylee H. Maclachlan, Urvi A. Shah, Malin Hultcrantz, Issam S. Hamadeh, Andriy Derkach, David Nemirovsky, Sergio A. Giralt, Sham Mailankody, Saad Z. Usmani, Hamza Hashmi; Outcomes in frail patients receiving BCMA-directed bispecific antibodies for relapsed/refractory multiple myeloma. Blood Adv 2025; 9 (15): 4016–4022. doi: https://doi.org/10.1182/bloodadvances.2025015973  (https://ashpublications.org/bloodadvances/article/9/15/4016/537099/Outcomes-in-frail-patients-receiving-BCMA-directed)

SWIFT-seq enables comprehensive single-cell transcriptomic profiling of circulating tumor cells in multiple myeloma and its precursors — Nature Cancer (August 2025) 

What is the purpose of the study? 
Multiple myeloma is a cancer of plasma cells in the bone marrow. It's often detected after earlier, less serious conditions. However, bone marrow biopsies (the current standard for diagnosis) are invasive and sometimes unreliable. 

This study introduces a new, less invasive method called SWIFT-seq, which uses single-cell sequencing to analyze tiny amounts of cancer cells found in the blood, known as circulating tumor cells (CTCs). 

How was the research conducted? 

• Researchers studied blood and bone marrow samples from 101 patients and healthy individuals. 
• They used advanced sequencing to: 

          - Count CTCs using a new strategy. 
          - Identify genetic changes in these cells. 
          - Measure how fast the cancer is growing. 
          - Track changes in the cancer over time. 

What is the key insight? 
Researchers developed a model showing how tumor growth, genetic features, and the ability of cells to enter the bloodstream all affect the number of CTCs found in the blood. 

SWIFT-seq detected CTCs in 90% of patients across all stages. It worked even better in those with SMM (95%) and newly diagnosed MM (94%). The test also helps scientists understand how myeloma spreads in the body. 

Why this study matters 
This new method could allow for easier, safer, and more frequent blood-based tests for diagnosing, monitoring, and predicting outcomes in multiple myeloma—without needing frequent bone marrow biopsies. 

SWIFT-seq only requires a blood sample but still gives doctors detailed information about the cancer. This new blood test could greatly improve how doctors detect and track multiple myeloma and its early stages—MGUS and SMM. 

The new blood test looks at circulating tumor cells (CTCs)—cancer cells that are floating in the blood. It provides a genetic profile of these cells, helping doctors understand how aggressive the cancer is and what treatments might work best. 

SWIFT-seq is a promising non-invasive tool that could make myeloma diagnosis and monitoring easier, more accurate, and more informative. 
 

Reference: 
Lightbody, E.D., Sklavenitis-Pistofidis, R., Wu, T. et al. SWIFT-seq enables comprehensive single-cell transcriptomic profiling of circulating tumor cells in multiple myeloma and its precursors. Nat Cancer (2025). https://doi.org/10.1038/s43018-025-01006-0  (https://www.nature.com/articles/s43018-025-01006-0)

Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma — Blood Cancer Journal (August 2025) 

Background 
Patients with relapsed/refractory multiple myeloma (RRMM) who have already tried several treatments (including daratumumab) have limited options and often poor outcomes. 

Two CAR T-cell therapies, ABECMA® (idecabtagene vicleucel or ide-cel) and CARVYKTI® (ciltacabtagene autoleucel or cilta-cel) have shown promise and are now used earlier in treatment. 

What is the purpose of the study? 
The study looked at 171 patients treated with CAR T-cell therapy from 2018-2024, with 144 patients who are daratumumab-refractory and 27 patients who are non-refractory. Outcomes such as response to treatment, survival, and side effects were compared. 

The purpose of the study is to see if previous resistance to daratumumab affects how well patients respond to CAR T-cell therapy. 

Definitions: 

• Daratumumab-refractory: Disease worsened within 60 days after stopping daratumumab. 
• Non-refractory: Disease did not worsen soon after stopping. 
• CAR T-cell therapy: A treatment that uses a patient’s own immune cells to fight cancer. 

What were the key findings?  
Overall response rate was 82% for all patients—similar in both groups. 

• Progression-free survival (PFS): How long the disease stayed under control was about the same in both groups. 
• Overall survival (OS): Median survival was 34 months, with no major difference between groups. 
• Side effects were manageable and expected for this type of treatment. 

Risk factors for poor outcomes 
Certain features were linked to worse outcomes regardless of daratumumab status: 

• High-risk genetic mutations 
• Disease outside the bone marrow (extramedullary disease) 
• Heavy disease burden 
• Previous treatment with BCMA-targeting drugs 
• Use of CAR T products other than cilta-cel 

Conclusion 

• Being resistant to daratumumab did not lead to worse outcomes after CAR T-cell therapy. 
• CAR T remains effective whether patients were daratumumab-refractory or not. 
• However, disease biology (like genetic risk and disease location) had a stronger impact on outcomes than prior drug resistance. 

Why this study matters for patients 
If you have multiple myeloma and previously received daratumumab, especially if it stopped working, you may still benefit from CAR T-cell therapy. Other factors—like your overall disease risk—are more important in predicting how well CAR T might work for you. 

Reference: 
Sebastian, T., Rajeeve, S., Farzana, T. et al. Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma. Blood Cancer J. 15, 137 (2025). https://doi.org/10.1038/s41408-025-01343-4  (https://www.nature.com/articles/s41408-025-01343-4)

 
Clinical Trials 

BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study — Leukemia & Lymphoma (July 2025) 

What is the purpose of the study? 
This early-phase clinical trial tested AMG 420, a new type of immune therapy that targets B-cell maturation antigen (BCMA), a protein found on multiple myeloma cells. AMG 420 helps the body's T-cells find and attack the cancer. This study showed that AMG 420 is a promising treatment for relapsed or refractory multiple myeloma (RRMM), confirming BCMA as a valid treatment target. 

What were the results of the trial? 
While the response rates were slightly lower than in an earlier trial, the therapy still showed good safety and tolerability, especially at doses of 400 and 600 μg/day. The most common side effect was cytokine release syndrome (CRS)—a flu-like immune reaction—reported in 78% of patients, but no severe cases occurred. Side effects were manageable, especially with newer treatments like tocilizumab and dexamethasone that help prevent or reduce CRS. 

Infections remain a concern with this type of therapy, but the rates in this study were lower than in similar treatments. Neurologic side effects were rare and mild, and no serious nerve problems were reported. 

Compared to similar drugs, AMG 420 had a moderate response rate (34.8%), which was slightly better overall than earlier results, but not as high as some newer BCMA-targeted therapies like teclistamab or CAR T-cell therapy. However, AMG 420 did not cause eye problems or high-grade CRS, which are common in other treatments. 

A limitation of AMG 420 is that it requires continuous intravenous (cIV) infusion due to its short half-life, making it less convenient than newer options. 

Why this study matters 
AMG 420 was the first BCMA-targeted T-cell therapy tested in multiple myeloma and helped shape how these treatments are used today. It confirmed BCMA as a powerful target, taught doctors how to manage side effects like CRS, and laid the groundwork for newer therapies that are now offering better responses with easier dosing. 

Reference: 
Rodriguez, C., Rodriguez, T., Kentos, A., Driessen, C., Sunami, K., Lesokhin, A. M., … Quach, H. (2025). BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study. Leukemia & Lymphoma, 1–10. https://doi.org/10.1080/10428194.2025.2528115  (https://www.tandfonline.com/doi/full/10.1080/10428194.2025.2528115#abstract)

Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial — The Lancet Haematology (August 2025) 

Background 
Older adults who are not eligible for stem cell transplants often receive combination treatments for newly diagnosed multiple myeloma. This study compared three different treatment regimens to find out which works best, especially considering patients’ frailty and ability to tolerate side effects. 

What is the purpose of the study? 
Researchers compared: 

1. VMP-Rd – a combination of bortezomib, melphalan, prednisone, then lenalidomide and dexamethasone 
2. KRd – carfilzomib, lenalidomide, and dexamethasone 
3. D-KRd – same as KRd, but with the addition of daratumumab, an immune therapy 

They looked at how well each treatment cleared the cancer (called MRD negativity) and how well patients tolerated side effects. 

What are the key results? 

• MRD negativity: 

          - D-KRd: 61% of patients had no detectable cancer 
          - KRd: 54% had no detectable cancer 
          - VMP-Rd: Only 27% had no detectable cancer 

• Fewer side effects: Serious white blood cell drops (neutropenia) were less common with KRd (24%) compared to VMP-Rd (40%) and D-KRd (41%). 
• Infections and deaths: Serious infections occurred in 12–16% of patients across all groups. Deaths from treatment side effects were highest in the D-KRd group (8%) 

Why this study matters 

• KRd and D-KRd were more effective than VMP-Rd in eliminating cancer. 
• KRd had fewer severe side effects and may be a safer option for frailer patients. 
• The results support using personalized treatment based on frailty and considering four-drug (quadruplet) therapy when appropriate. 

Reference: 
Mateos MV, Paiva B, Cedena MT, Puig N, Sureda-Balari AM, de la Calle VG, Oriol A, Ocio EM, Rosiñol L, Montes YG, Bargay J, García MEG, Lakhwani S, Payer AR, Suarez-Cabrera A, Blanchard MJ, Garzón S, Montero FC, Cabañas V, de Oteyza JP, Gironella M, Martinez-Lopez J, Casasús AIT, Delgado-Beltrán MP, Prieto E, Lahuerta JJ, Bladé J, San-Miguel J. Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial. Lancet Haematol. 2025 Aug;12(8):e588-e598. doi: 10.1016/S2352-3026(25)00143-7.  (https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00143-7/abstract) 

Carfilzomib–lenalidomide–dexamethasone versus lenalidomide–dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial — The Lancet Haematology (August 2025) 

Background 
Before newer therapies were introduced, the standard first-line treatment for newly diagnosed multiple myeloma patients who couldn’t have a stem cell transplant was lenalidomide plus dexamethasone. This study tested whether adding carfilzomib (a newer drug) to that combination would improve outcomes. 

What is the purpose of the EMN20 trial? 
The EMN20 trial aimed to determine whether adding carfilzomib to the standard treatment of lenalidomide and dexamethasone could improve outcomes—specifically, measurable residual disease (MRD) negativity and progression-free survival—in patients with newly diagnosed multiple myeloma who are not eligible for a stem cell transplant. 

What are the key results? 

• MRD negativity (no detectable disease after 2 years): 60% of patients on the 3-drug combo had no detectable disease; 0% of patients on standard treatment had this response 
• Progression-free survival: Patients on the 3-drug combo stayed in remission significantly longer; Median survival time without progression wasn’t reached in the carfilzomib group, while it was about 21 months in the standard group 
• Side Effects: 

         - Most common serious side effects in the 3-drug group: low white blood cells, low platelets, diarrhea, and heart issues 
         - COVID-19-related pneumonia was the most common serious event in both groups 
         - Some deaths occurred in both groups, mostly related to infections or heart conditions 

Adding carfilzomib to lenalidomide and dexamethasone significantly improved the chances of having no detectable disease and helped patients stay in remission longer. The treatment did come with more side effects, but they were generally manageable. 

Why this study matters 
For patients who aren’t eligible for a stem cell transplant, adding carfilzomib may offer a stronger and deeper response to treatment, although it may also increase side effects. This option might be worth discussing with your doctor, especially in the context of newer treatment combinations. 

Reference: 
Bringhen S, Cani L, Antonioli E, Derudas D, Fazio F, Larocca A, Ronconi S, Cellini C, Falcone AP, Accardi F, Liberati AM, Galieni P, Belotti A, Cafro AM, Ria R, Benevolo G, Vincelli ID, Mannina D, Lotti F, Bruno B, Marasco V, Mazza R, Tosi P, Rivolti E, Boccadoro M, D'Agostino M. Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2025 Aug;12(8):e621-e634. doi: 10.1016/S2352-3026(25)00162-0.  (https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00162-0/abstract)

Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials — Blood Advances (August 2025) 

What is the purpose of the study? 
Researchers studied belantamab mafodotin — an antibody-drug conjugate used to treat patients with relapsed or refractory multiple myeloma, in combination with standard therapies in the DREAMM-7 and DREAMM-8 clinical trials. 

What are the key findings of the study?  

• Treatment was effective: Belantamab combinations helped patients live longer without their cancer worsening (progression-free survival) and improved overall survival in some cases. 
• Eye-related side effects (Ocular events): Some patients experienced eye problems, such as dry eyes, sensitivity to light, or blurry vision. These were most common in the first 3 months of treatment. 
• Manageable side effects: Eye problems were successfully managed by changing the dose or delaying treatment. Most patients did not have to stop treatment because of eye issues. 
• Dosing was adjusted over time: By 9 months into treatment, dosing was often spaced out to once every 8–12 weeks (instead of more frequently), helping reduce side effects. 
• Vision usually improved: If vision problems occurred, they typically got better within 12 weeks. 
• Most patients still responded: Even with dose delays or reductions, most patients responded to treatment—and some saw their response deepen after adjusting the dose. 

Why this study matters 
Belantamab mafodotin, when combined with standard treatments, offers important benefits for people with relapsed or refractory multiple myeloma. While eye side effects are common, they are usually temporary and manageable, allowing most patients to stay on treatment and benefit from it. 

Reference: 
Maria-Victoria Mateos, Suzanne Trudel, Hang Quach, Pawel Robak, Meral Beksac, Ludek Pour, Marek Hus, Kihyun Kim, Vera Zherebtsova, Sosana Delimpasi, Tomas Jelínek, Christopher Ward, P. Joy Ho, Vladimir I. Vorobyev, Marcelo Pitombeira Lacerda, Gracia Aparecida Martinez, Ivan Spicka, Jakub Radocha, Michele Cavo, Claudio Cerchione, Chengcheng Fu, Kazuhito Suzuki, Rachel Rogers, Amy Phillips-Jones, Zhaohui Wang, Hena Baig, Jodie Wilkes, Xiaoou L. Zhou, Eric Lewis, Lydia Eccersley, Neal Sule, Prani Paka, Joanna B. Opalinska, Pralay Mukhopadhyay, Vania Tietsche de Moraes Hungria, Meletios Athanasios Dimopoulos; Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials. Blood Adv 2025; bloodadvances.2025016949. doi: https://doi.org/10.1182/bloodadvances.2025016949  (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025016949/546495/Modification-of-Belantamab-Mafodotin-Dosing-to)

Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results — Blood (August 2025) 

What is the purpose of the study? 
This study looked at the long-term effects of adding daratumumab to standard treatment in newly diagnosed multiple myeloma patients who were eligible for a stem cell transplant. Daratumumab is a targeted therapy that helps the immune system find and destroy myeloma cells. 

What are the key findings of the study? 

• Better disease control: Adding daratumumab to standard induction and consolidation treatment led to deeper and longer-lasting responses, meaning fewer detectable myeloma cells (MRD negativity). 
• Long-term benefit: After more than 6.5 years of follow-up, patients who received daratumumab plus standard treatment (D-VTd) had better progression-free survival (PFS)—they lived longer without their disease getting worse. 
• Maintenance therapy works: Continuing daratumumab as maintenance treatment after initial therapy helped all patients, even those who didn’t receive daratumumab at first or who already had low levels of cancer. 
• Effective for all risk levels: The benefits were seen in patients regardless of their genetic risk factors or disease stage. 

Why this study matters 
Using daratumumab during and after initial treatment leads to stronger and longer-lasting responses and better long-term outcomes in newly diagnosed multiple myeloma patients. 

Reference: 
Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hebraud, Cyrille Hulin, Marie C. Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jérôme Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W. C. J. van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuilleme, Pieter Sonneveld; Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results. Blood 2025; 146 (6): 679–692. doi: https://doi.org/10.1182/blood.2024027620  (https://ashpublications.org/blood/article-abstract/146/6/679/536289/Daratumumab-bortezomib-thalidomide-dexamethasone?redirectedFrom=fulltext)

Symptomatic progression-free survival as an emerging patient-centered endpoint in multiple myeloma: a secondary analysis of MagnetisMM-3 trial data — BMC Cancer (August 2025) 

What is the purpose of this study? 
Traditionally, progress in multiple myeloma is measured by how the disease grows or responds to treatment. This study aimed to create a new way to measure progress that includes both medical results and patient-reported symptoms—such as pain, fatigue, and poor mobility. 

What were the methods used? 

• Researchers did a systematic literature review (SLR) of past studies to identify common symptoms of myeloma. 
• Experts then agreed on which symptoms are most linked to disease progression. 
• Using data from a clinical trial (MagnetisMM-3), the team studied how changes in these symptoms related to disease worsening or death. 
• A new measure called Symptomatic Progression-Free Survival (SPFS) was created. This includes either: 

               - Traditional disease progression or, 
               - A significant worsening of symptoms within 28 days (10-point drop in symptom scores) or, 
               - Death. 

What were the key findings? 

• Three symptoms—pain, fatigue, and poor mobility—were most strongly linked to worsening disease. 
• A worsening in these symptoms increased the risk of disease progression by 20–31%. 
• Most patients who had disease progression also experienced a decline in symptoms. 
• A small group (7%) progressed without symptom worsening, showing that disease can worsen without obvious signs. 
• Because of limited follow-up time, the median SPFS could not be calculated. 

Why these key findings matter 

• SPFS is the first measure in myeloma that combines how the disease grows with how patients feel. 
• It offers a more complete picture of a patient’s condition than traditional measures alone. 
• This could help doctors and researchers better evaluate treatments by considering both clinical results and quality of life. 
• It could also guide health authorities and policymakers in choosing treatments that truly benefit patients. 

Strengths 

• Used a careful, step-by-step method to choose symptoms that matter to patients. 
• Combined clinical trial data with expert opinions. 
• Helps address concerns that some clinical measures don’t reflect real patient experiences. 

Limitations 

• The study had a small sample size and short follow-up (7.5 months on average). 
• Patients who died early weren’t included in the symptom analysis. 
• The evolving myeloma treatment landscape (like MRD testing) isn’t fully captured by symptom-based tools. 
• Patient opinions were not directly included in the expert panel—future studies should include patient voices. 

Why this study matters 
This study highlights the importance of putting patients at the center of treatment evaluation in myeloma. By combining clinical data with symptom reports, researchers created a new, more meaningful way to measure how treatments affect both the disease and the patient’s quality of life. More research is needed to confirm these findings, but this work is a promising step toward more patient-focused care in myeloma. 

Reference: 
Kortüm, M., Theurich, S., Farrell, J. et al. Symptomatic progression-free survival as an emerging patient-centered endpoint in multiple myeloma: a secondary analysis of MagnetisMM-3 trial data. BMC Cancer 25, 1288 (2025). https://doi.org/10.1186/s12885-025-14724-6  (https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14724-6)

U.S. Food and Drug Administration (FDA) 

FDA Issues Complete Response Letter for DARZALEX FASPRO® sBLA; Cites Facility Inspection Issues as Cause of Delay in Approval 

In a recent news release (https://www.jnj.com/media-center/press-releases/update-on-u-s-regulatory-review-of-supplemental-biologics-license-application), Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the supplemental

Biologics License Application (sBLA) of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). The FDA has declined the drug’s approval for the treatment of newly diagnosed, transplant-ineligible multiple myeloma, citing facility inspection issues as the cause. 

Johnson & Johnson clarified that "the CRL is based on observations from facility inspections and is not related to the robust safety and efficacy data submitted for this application. No new clinical studies were requested. [Johnson & Johnson is]committed to resolving outstanding observations in a timely manner, with the goal of advancing this indication as soon as possible." 

Furthermore, Johnson & Johnson elaborated the following key facts: 

• No impact globally to the product supply or commercial availability of DARZALEX FASPRO®. 
• DARZALEX FASPRO® remains approved and available for all nine multiple myeloma U.S. indications. 
• Regulatory submissions and approvals in other global markets are ongoing. The CEPHEUS indication was recently approved by the European Commission. 

Yusri Elsayed, M.D., M.H.Sc., Ph.D. Global Therapeutic Area Head, Oncology, Innovative Medicine, Johnson & Johnson stated: “We are working closely with the FDA and are confident in our ability to promptly resolve the matter. Healthcare professionals and patients can be assured of no impact to the current use or supply of DARZALEX® and DARZALEX FASPRO®, which are foundational therapies for treating multiple myeloma.” 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.  (https://www.myeloma.org/news-events/multiple-myeloma-news)