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 the latest clinical guidelines in myeloma, including the European Myeloma Network (EMN) Group consensus statement on the use of next-generation sequencing (NGS) for prognostic stratification for newly diagnosed patients. Read the New England Journal of Medicine published review, authored by IMF Chairperson of the Board Dr. S. Vincent Rajkumar and IMF Scientific Advisory Board Member Dr. Shaji Kumar, on monoclonal gammopathy of undetermined significance (MGUS), as well as a paradigm-changing paper on MGUS and smoldering myeloma, published in the Journal of Clinical Oncology.
Additionally, catch up on some of the latest in clinical trials and FDA drug approvals — including the results of the randomized phase 3 AMN003 study, published in Blood Cancer Journal; and FDA approval of GSK’s Blenrep® (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone (BVd) for the treatment of relapsed/refractory multiple myeloma.
Guidelines and Recommendations
Singapore Myeloma Study Group consensus guidelines for the management of patients with newly diagnosed multiple myeloma — Annals, The Academy of Medicine, Singapore (September 2025, Review)
Summary
This review article discusses the Singapore Myeloma Study Group's consensus guidelines for the management of newly diagnosed multiple myeloma, focusing on advancements in diagnosis, treatment, and supportive care.
The Singapore Myeloma Study Group provides consensus guidelines for managing newly diagnosed multiple myeloma, emphasizing advancements in diagnostics and treatment.
The guidelines are evidence-based and intended for healthcare professionals managing multiple myeloma.
Key sections include diagnosis, supportive care, response assessment, and management strategies for transplant-eligible and ineligible patients.
Diagnosis and risk assessment
• Multiple myeloma is diagnosed when there are 10% or more abnormal plasma cells in the bone marrow or a biopsy-proven tumor, along with organ damage (SLiM-CRAB criteria).
• Tests include blood and urine studies, bone marrow biopsy, and imaging (low-dose whole-body CT scan).
• Risk is assessed using genetic tests and blood markers, which guide treatment choices.
Supportive care
Supportive care addresses complications like:
◦ High calcium levels – treated with fluids and medications like zoledronic acid.
◦ Kidney problems – managed with hydration and early treatment.
◦ Anemia – may require medications that stimulate red blood cell production.
◦ Bone damage – bisphosphonates are standard; surgery may be needed for fractures.
Infection and clot prevention
Myeloma patients are more prone to infections and blood clots.
◦ Antiviral medications are recommended with certain treatments.
◦ Vaccinations (especially inactivated ones) are encouraged.
◦ Blood clot prevention is important when using certain drugs.
Monitoring and response
• Regular monitoring helps assess how well treatment is working.
• Minimal residual disease (MRD) testing can detect very small amounts of cancer and guide future treatment.
• Advanced imaging (like PET scans) helps spot disease outside the bone marrow.
Treatment for transplant-eligible and transplant-ineligible patients
1. Transplant-eligible patients
• Typically younger and physically fit.
• Induction therapy (often bortezomib-based) is followed by autologous stem cell transplant (ASCT).
• Newer drug combinations (like those including daratumumab) improve outcomes.
• High-dose melphalan is used before transplant.
• Maintenance therapy (like lenalidomide) is recommended to prolong remission.
2. Transplant-ineligible patients
• Often older or with other health issues.
• Treatment is tailored based on frailty.
• Preferred regimens include lenalidomide- or daratumumab-based therapies.
• Maintenance therapy is recommended if tolerated, usually for about 2 years or longer.
Elderly and frail patients
• Special assessments help predict treatment tolerance.
• Frailty and other health conditions influence treatment choices.
• Simplified frailty scores are used to personalize care.
New therapies
• New drugs like daratumumab and isatuximab offer better outcomes, especially when added to standard treatments.
• Research continues to improve options for all patient groups.
Key takeaways for patients
• Myeloma is complex but manageable with the right care team and treatment plan.
• Regular follow-up, supportive care, and staying informed about options are crucial.
• Newer therapies and personalized approaches are improving survival and quality of life.
Reference:
de Mel S, Tso AC, Soekojo CY, Ooi MG, Lim CC, Teo C, Chen YX, Tan M, Manjeri A, Lee ZY, Tan D, Lee LK, Cao L, Goh YT, Nagarajan C, Chng WJ. Singapore Myeloma Study Group consensus guidelines for the management of patients with newly diagnosed multiple myeloma. Ann Acad Med Singap. 2025 Sep 25;54(9):561-584. doi: 10.47102/annals-acadmedsg.202532.
Management of relapsed multiple myeloma: A British Society of Haematology and UK Myeloma Society guideline — British Journal of Haematology (October 2025)
Summary
This guideline helps doctors manage relapsed or refractory multiple myeloma (RRMM) after at least one previous therapy. It offers advice based on the best available evidence but is not a replacement for personal medical decisions made between patients and healthcare teams.
How were the guidelines developed?
• Experts reviewed high-quality research studies up to 2024.
• Most recommendations are based on phase II and III clinical trials.
• The guideline was reviewed by UK myeloma experts, professional groups, and the charity Myeloma UK.
Key points
• There are now many treatment options for myeloma, leading to better patient outcomes.
• However, this also makes choosing the best treatment more complex.
• Treatment availability may vary across the UK (England, Scotland, Wales, Northern Ireland).
• Instead of offering one fixed treatment path, the guideline supports personalized treatment plans based on:
◦ The patient’s health and preferences
◦ How the disease is behaving
◦ How well previous treatments worked and what side effects occurred
Why these guidelines matter
Personalized care, guided by current research and tailored to each patient’s needs, offers the best chance of successful treatment for relapsed myeloma.
Reference:
Jenner M, Boyd K, Choudhuri S, Parrish C, Garg M, Stern S. Management of relapsed multiple myeloma: A British Society of Haematology and UK Myeloma Society guideline. Br J Haematol. 2025; 00: 1–33. https://doi.org/10.1111/bjh.70149
Updated guidelines in the treatment of myeloma bone disease in 2025: consensus statement by the Medical and Scientific advisory group of Australia (MSAG) to myeloma Australia — Expert Review of Hematology (October 2025)
What is bone disease in myeloma?
Multiple myeloma can weaken bones, often causing pain or fractures. This condition is known as myeloma bone disease (MBD).
Common treatments
Medicines called bisphosphonates (like zoledronic acid and pamidronate) are commonly used to protect and strengthen bones in people with myeloma. A newer medicine called denosumab may be a good option, especially for those with kidney problems.
Key recommendations
• Bisphosphonates are recommended for up to 2 years. Treatment intervals may be extended if the disease is stable.
• Denosumab works as well as zoledronic acid and is safer for people with kidney issues, but it can cause low calcium levels, so monitoring is important.
• Other treatments include radiation and surgery in certain cases.
What patients need to know
• The best treatment plan depends on your overall health, kidney function, and how your disease responds to therapy.
• Some side effects of bone treatments, although rare, can be serious—so regular check-ups are important.
• New research is looking at ways to better guide treatment using bone markers and to support bone-building in addition to slowing bone loss.
Reference:
Yong, A., Vandyke, K., Augustson, B., McCaughan, G., Talaulikar, D., Szabo, F., … Lee, C. H. (2025). Updated guidelines in the treatment of myeloma bone disease in 2025: consensus statement by the Medical and Scientific advisory group of Australia (MSAG) to myeloma australia. Expert Review of Hematology. https://doi.org/10.1080/17474086.2025.2574716
European Myeloma Network Group Consensus Statement on the use of next-generation sequencing for prognostic stratification of newly diagnosed multiple myeloma — HemaSphere (October 2025)
What is the purpose of this consensus statement?
This paper explores whether a modern genetic test called Next-Generation Sequencing (NGS) could help (or even replace) the current standard test, fluorescence in situ hybridization (FISH), for evaluating risk in patients newly diagnosed with multiple myeloma (NDMM).
Understanding a patient's genetic profile helps doctors:
• Better predict how aggressive the myeloma is (prognosis)
• Choose the most effective treatments
• Identify who may benefit from future therapies
Key takeaways for patients
What is NGS?
Next-Generation Sequencing (NGS) is a powerful test that can detect many types of genetic changes in cancer cells (including mutations, chromosome changes, and gene rearrangements) all at once.
Should NGS replace FISH?
• Not yet. Experts recommend using NGS alongside FISH for now.
• In the future, NGS may replace FISH once it becomes more standardized and accessible.
What can NGS detect?
• High-risk features like TP53 mutations and chromosome deletions
• Specific gene changes that might make a patient respond better to certain treatments (e.g., BCL2 inhibitors, CAR-T cell therapy)
Who should get NGS testing?
Experts recommend:
• All newly diagnosed fit patients, especially those who may receive modern multi-drug treatment or clinical trials
• Not routinely needed for very elderly or frail patients where results wouldn't change treatment
Should NGS be repeated later?
Yes — especially:
• At relapse (when the disease returns)
• Before starting advanced therapies like CAR-T, bispecific antibodies, or venetoclax
Why is NGS useful?
• Gives a comprehensive picture of your disease
• Helps personalize treatment
• May guide future clinical trials and drug development
What’s next?
Future advancements may include:
• Using blood tests instead of bone marrow for genetic analysis
• Whole genome sequencing (WGS) to uncover even more useful genetic info
• More widespread use as costs decrease and technology improves
Why this consensus statement matters
NGS is a promising tool that may lead to better treatment decisions and outcomes in multiple myeloma. While it's not yet a full replacement for current testing methods, it's a big step toward personalized medicine.
Reference:
Bolli, N., D'Agostino, M., Bagratuni, T., Boccadoro, M., Cavo, M., Driessen, C., Einsele, H., Engelhardt, M., Gay, F., Gutiérrez, N.C., Hájek, R., Holien, T., João, C., Kaiser, M., Kortüm, K.M., Leypoldt, L., Moreau, P., Musto, P., Ocio, E.M., Raab, M.S., Rasche, L., Schjesvold, F., Sevcikova, T., Terpos, E., Touzeau, C., Van de Donk, N.W.C.J., van Duin, M., Weisel, K., Zamagni, E., Cupedo, T., Sonneveld, P. and Terragna, C. (2025), European Myeloma Network Group Consensus Statement on the use of next-generation sequencing for prognostic stratification of newly diagnosed multiple myeloma. HemaSphere, 9: e70216. https://doi.org/10.1002/hem3.70216
Review
Is There a Universal Standard of Care for Frontline Therapy in Multiple Myeloma? — Clinical Advances in Hematology & Oncology (September 2025, Q&A)
In this Q&A interview by Clinical Advances in Hematology & Oncology, Sagar Lonial, MD — IMF Scientific Advisory Board Member, Professor and Chair at the Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, GA) addresses the following questions.
(EDITOR’S NOTE: Questions and answers have been edited to be concise, clear, and comprehensible for patients and general readers.)
What is the most common frontline treatment for multiple myeloma?
The standard treatment for fit patients in the U.S. is a four-drug regimen called Dara-VRd: daratumumab (a monoclonal antibody), lenalidomide (an immunomodulator), bortezomib (a proteasome inhibitor), and dexamethasone (a steroid). This may be followed by stem cell transplant, more Dara-VRd, and lenalidomide maintenance. The PERSEUS trial showed that this approach significantly improves survival.
What are other frontline options?
• Isa-VRd (using isatuximab instead of daratumumab) for transplant-ineligible patients, based on the IMROZ trial.
• Dara-KRd and Isa-KRd (replacing bortezomib with carfilzomib), shown to achieve deep responses in various trials, especially in high-risk or transplant-eligible patients.
What are common side effects and how do you choose a regimen?
• All CD38-targeting drugs (like daratumumab or isatuximab) increase the risk of infections.
• Some regimens cause more neutropenia.
• Choice depends on patient fitness:
◦ Fit patients: Four-drug regimens like Dara-VRd or Isa-KRd.
◦ Frail patients: Less intensive options, such as Dara-Rd, are preferred.
Should age or transplant eligibility determine treatment?
Not necessarily. U.S. doctors focus more on whether patients are fit or frail, rather than basing on age alone. Fit patients, regardless of age, may still benefit from four-drug regimens. Frail patients may need dose adjustments or fewer drugs.
Is treatment variation across doctors a concern?
Variation exists but often reflects personalized care. Some patients initially considered ineligible for transplant may improve with treatment and become eligible later.
How does access affect treatment?
Access plays a major role. Only about 30% of eligible patients get referred for transplant, and Black patients are less likely to receive advanced therapies, leading to worse outcomes.
Will treatments become more standardized or stay diverse?
More standardization is likely. Most treatments rely on a similar set of core drugs, and new therapies like CAR T-cell therapy and bispecific antibodies are on the horizon.
How do trial results compare to real-world patients?
Trial patients tend to be younger and healthier. In real practice, doctors need to tailor regimens and closely monitor side effects, especially in older or frailer patients.
What advice is there for community oncologists treating myeloma?
• Partner with a myeloma center to stay updated.
• Communicate regularly with experts to make informed treatment and dose adjustments.
• Stay current, as treatment advances quickly—often faster than guidelines can keep up.
Reference:
Lonial S. Is there a universal standard of care for frontline therapy in multiple myeloma? Clin Adv Hematol Oncol. 2025 Sep;23(6):379-381
Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management — Advances in Hematology (September 2025)
What is high-risk multiple myeloma?
Some myeloma patients (20–25%) have “high-risk” genetic features—like del(17p), t(4;14), t(14;16), and gain(1q)—that make the disease more aggressive and harder to treat.
Treatment overview for newly diagnosed patients
1. Transplant-eligible patients
Standard induction: Most start with 3- or 4-drug combos, often including:
◦ VRd (bortezomib, lenalidomide, dexamethasone)
◦ D-VRd (adds daratumumab)
◦ KRd (uses carfilzomib instead of bortezomib)
◦ Dara-KRd, Isa-KRd (adds anti-CD38 antibodies like daratumumab or isatuximab)
Key findings:
◦ Adding daratumumab or isatuximab may improve outcomes.
◦ Intensive regimens (like Dara-KRd, Isa-KRd) show deep responses, even in high-risk patients.
◦ Some studies show better results with 4 or 5 drugs, especially in those with 2 or more high-risk markers.
2. Transplant-ineligible patients
Preferred regimens:
◦ DRd (daratumumab, lenalidomide, dexamethasone)
◦ VRd-lite (lower-dose for frail patients)
◦ Isa-VRd and DVMP also show benefits.
• Takeaway: Adding anti-CD38 antibodies like daratumumab or isatuximab improves response, even in high-risk patients.
Stem cell transplant (ASCT)
• Still a core treatment for eligible patients.
• High-risk patients benefit more from early transplant, and some may benefit from tandem (double) transplants.
• Deep responses (measured by MRD-negative status) are more likely with transplant.
Consolidation and maintenance
• Consolidation (extra treatment after transplant) is not routine but may help high-risk patients.
• Maintenance therapy is essential:
◦ Lenalidomide alone is standard, but less effective in high-risk cases.
◦ Adding bortezomib (a proteasome inhibitor) helps with high-risk disease.
◦ Anti-CD38 antibodies (daratumumab, isatuximab) may further improve maintenance outcomes.
New and emerging therapies
• CAR-T cell therapy and bispecific antibodies show very promising early results in high-risk patients.
◦ These therapies can lead to deep, durable responses, even in patients with aggressive disease.
◦ Clinical trials are testing them as first-line options.
What is the bottom line for patients?
• High-risk myeloma is tougher to treat, but treatment is improving.
• Combination therapies (including newer antibodies and drugs) offer better responses.
• Stem cell transplant, maintenance, and clinical trials are important parts of care.
• New immunotherapies like CAR-T and bispecific antibodies offer hope for the future.
Reference:
Yasar, Fatma Zehra, Gorshein, Elan, Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management, Advances in Hematology, 2025, 6622365, 16 pages, 2025. https://doi.org/10.1155/ah/6622365
Monoclonal Gammopathy of Undetermined Significance — New England Journal of Medicine (October 2025)
What is MGUS?
Monoclonal gammopathy of undetermined significance (MGUS) is a common condition affecting about 5% of people over age 50. It is not cancer, but it is considered a precursor to certain blood cancers like multiple myeloma, plasmacytoma, and Waldenström’s macroglobulinemia.
In MGUS, abnormal plasma cells in the bone marrow produce identical antibodies (called monoclonal or M proteins) in small amounts. Most people with MGUS have no symptoms and never develop cancer. However, in some cases, MGUS can cause serious problems or progress to cancer.
Why is MGUS important?
• MGUS can progress to cancer at a rate of about 1% per year.
• It can also lead to non-cancer complications that affect organs — this is known as Monoclonal Gammopathy of Clinical Significance (MGCS).
• Regular monitoring is important to catch changes early.
Types of MGUS
There are three types based on the kind of abnormal protein:
• IgM MGUS
• Non-IgM MGUS (mostly IgG or IgA)
• Light-chain MGUS
Each type carries different risks for progression.
Diagnosis and tests
• Blood tests are key: M protein level, free light chain (FLC) ratio, kidney function, calcium.
• Bone marrow biopsy is usually not needed in low-risk cases.
• Online tools and risk models help doctors decide who needs further testing.
Risk factors for progression
You may be at higher risk of developing cancer if you have:
• M protein level ≥ 1.5 g/dL
• IgA or IgM subtype
• Abnormal FLC ratio
People with all three of these factors have a 58% risk of progression in 20 years, while those with none have only 5%.
Monitoring and management
• No treatment is needed unless MGUS progresses.
• Regular follow-ups every 6 to 12 months are important.
• Monitoring helps catch any signs of cancer or organ damage early.
• Current research is exploring whether some high-risk cases should be treated earlier.
Screening
• General screening for MGUS is not recommended.
• Screening is recommended for people with:
◦ Two or more close relatives with MGUS or related conditions
◦ Black individuals with a close relative affected
• Currently, the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) randomized trial “is testing the effect of screening for MGUS on malignant and nonmalignant progression, but overall survival results are not expected for several years.”
Why constant monitoring of MGUS matters
MGUS is usually harmless, but it needs ongoing monitoring because of the small risk of serious complications. If you have MGUS, regular check-ups and communication with your doctor can help ensure early detection of any changes.
Reference:
Rajkumar SV, Kumar S. Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2025 Oct 2;393(13):1315-1326. doi: 10.1056/NEJMra2412716.
Treatment of transplant-ineligible multiple myeloma — Blood Research (October 2025)
Background
Treatment for multiple myeloma in people who are ineligible for stem cell transplant (often older or frail patients) has improved significantly over time. Older treatments used chemotherapy (like melphalan), but newer options now include targeted therapies and monoclonal antibodies, which are more effective and often better tolerated.
Key treatment advances
1. From chemotherapy to targeted therapy:
◦ Traditional treatments used chemotherapy.
◦ Newer regimens use drugs like:
▪Proteasome inhibitors (e.g., bortezomib),
▪Immunomodulatory drugs (e.g., lenalidomide),
▪Anti-CD38 monoclonal antibodies (e.g., daratumumab, isatuximab).
2. Combination treatments:
◦ Doublet (2 drugs), triplet (3 drugs), and quadruplet (4 drugs) combinations are now used.
◦ These aim to improve survival and achieve deep responses, measured by minimal residual disease (MRD) negativity—meaning almost no cancer is left.
Effective regimens
• VRd (bortezomib + lenalidomide + dexamethasone):
◦ Improved survival in younger patients.
◦ Requires dose adjustment in older adults.
• “RVD-lite”:
◦ A gentler version for older patients.
◦ High response rates with fewer side effects.
• Daratumumab combinations:
◦ D-VMP and D-Rd (adding daratumumab to standard regimens) showed better outcomes and deeper remissions.
◦ D-Rd is now widely used as the preferred first-line treatment for many older patients.
Newest developments
• Quadruplet therapies:
◦ Add anti-CD38 antibodies (daratumumab or isatuximab) to VRd.
◦ Shown to further improve remission and survival.
◦ Approved for patients under 80 years without severe frailty.
• Other promising approaches:
◦ KRd (carfilzomib + lenalidomide + dexamethasone) with or without daratumumab.
◦ Bispecific antibodies and CAR-T cell therapy are being studied for frontline treatment, showing strong early results—even in older patients.
Managing frailty in older adults
• Frailty is common in older myeloma patients and affects treatment tolerance.
• Tools now exist to assess frailty, and help doctors to tailor treatment.
• Studies show that even frail patients benefit from newer regimens like D-Rd.
• Steroid-reducing strategies are being tested to improve tolerability without losing effectiveness.
Conclusion
Treatment for multiple myeloma in patients who can’t receive a transplant has dramatically improved. The focus has shifted from just prolonging life to achieving deep remissions with manageable side effects, even in older and frail patients. The future includes more personalized treatments, less toxic options, and continued progress with advanced therapies like bispecific antibodies and CAR-T cells.
Reference:
Jung, J. Treatment of transplant-ineligible multiple myeloma. Blood Res. 60, 53 (2025). https://doi.org/10.1007/s44313-025-00102-5
Research
Real-World Treatment Patterns and Clinical Outcomes Among Patients With Triple-Class–Exposed and BCMA-Exposed Multiple Myeloma Within the United States — eJHaem (September 2025)
Background
Multiple myeloma often comes back after treatment. Many patients eventually receive multiple kinds of treatments, including three main drug classes (called “triple-class exposure” or TCE) and newer drugs that target a protein called BCMA. However, there is little information on how patients do after they’ve already tried all of these treatments.
What is the purpose of the study?
To understand how patients with myeloma, who have had both TCE and BCMA-targeted treatments, respond to further treatment in real-world settings.
How was the study conducted?
Researchers looked at U.S. insurance claims data from 656 patients with heavily treated myeloma who had previously received TCE and BCMA therapies and then started a new line of treatment.
Key findings
• On average, patients were 66 years old and had been living with myeloma for about 5.4 years.
• They had already received nearly 6 different lines of therapy.
• After TCE and BCMA treatments, doctors used 137 different treatment combinations, showing no clear standard treatment exists.
• Most common drugs used again were carfilzomib, pomalidomide, and bortezomib.
• Patients often reused drugs they had tried before.
• The median time before needing another treatment or death was only 6.8 months.
• The median time before stopping treatment or death was just 3.5 months.
Conclusion
Patients who have already received TCE and BCMA treatments have very limited options and poor outcomes with current therapies. There is no standard approach, and many patients quickly stop treatment or need another therapy. This highlights a critical need for new, effective treatments for people in this situation.
Why this study matters
As more patients reach this advanced stage of myeloma treatment, finding better options becomes increasingly urgent. This study helps doctors and researchers understand the challenges and guides future treatment development.
Reference:
H. S. Mian, J. S. Harper, H. H. Le, et al. “ Real-World Treatment Patterns and Clinical Outcomes Among Patients With Triple-Class–Exposed and BCMA-Exposed Multiple Myeloma Within the United States.” eJHaem 6, no. 5 (2025): e70145. https://doi.org/10.1002/jha2.70145
Interdisciplinary Management of Belantamab Mafodotin-Associated Ocular Toxicity in Clinical Practice — The Ocular Surface (October 2025)
Background
Belantamab mafodotin (Blenrep®) is a treatment for relapsed or refractory multiple myeloma (RRMM). While it can be effective, it often causes eye problems—especially damage to the cornea (the clear front part of the eye)—known as keratopathy.
What is the purpose of the study?
Doctors reviewed how often and how early eye side effects developed in real patients using belantamab, and how these eye issues affected treatment decisions (like dose changes, treatment breaks, or stopping the drug).
Key findings
• 93% of patients developed eye problems (keratopathy).
• Eye issues usually begin within 4 weeks of starting treatment.
• Treatment changes (dose reduction, break, or stopping) happened about 7 weeks in.
• The more severe the eye problem, the more likely doctors were to change or pause treatment.
• Dose reductions helped improve eye health, while treatment breaks sometimes made eye symptoms worse.
• Nearly all patients needed at least one change to how their treatment was managed.
• Eye problems were more common and more severe than what was seen in earlier clinical trials.
Conclusion
Eye side effects from belantamab are very common and often lead to changes in treatment. This highlights the need for regular eye check-ups starting early in treatment and strong teamwork between eye doctors and cancer doctors to protect patients’ vision.
Reference:
Mattan Arazi, Aya Wattad, Hila Magen, Abraham Avigdor, Nirit Agay, Yoav Berger, Irina S. Barequet, Interdisciplinary management of belantamab mafodotin-associated ocular toxicity in clinical practice, The Ocular Surface, Volume 38, 2025, Pages 324-329, ISSN 1542-0124, https://doi.org/10.1016/j.jtos.2025.09.003.
Advanced Multicolor Flow Cytometry Method for Multiple Myeloma — Clinical Lymphoma Myeloma & Leukemia (October 2025)
Background
Even with new treatments, multiple myeloma remains incurable, partly because the disease can appear in many different forms (called clonality). Accurately identifying these different forms is important for diagnosis and treatment planning.
What is the purpose of the study?
Researchers developed a new lab method using 14-color flow cytometry, a test that analyzes cells in detail, to better detect and visualize different types of cancerous plasma cells in myeloma.
Key features of this method:
• Uses a single test tube with a pre-mixed combination of antibodies (proteins that attach to markers on myeloma cells), making it simple and reliable.
• Can be stored for weeks without losing accuracy.
• Uses advanced computer analysis to create easy-to-read, 2D or 3D visual images of MM cell types.
• Helps identify unique clonal patterns in myeloma, even at different stages like diagnosis and relapse.
This new test helps doctors see how myeloma cells differ within each patient, making it easier to:
• Diagnose myeloma more precisely
• Track changes in the disease over time
• Choose personalized treatments based on each patient’s cancer type
Why this method matters
This new, easy-to-use method improves how doctors detect and understand MM cell types. It supports more accurate diagnosis and could lead to better, personalized treatment choices for people living with multiple myeloma.
Reference:
Noa Ofir, Ety Rozenberg, Omri Sharabi, Miri Zektser, Ory Rouvio, Roi Gazit, Advanced Multicolor Flow Cytometry Method for Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.09.014.
Current quality of life questionnaires are not relevant for assessing QOL issues in multiple myeloma patients in the era of modern therapies: results from a survey with myeloma patients and myeloma healthcare professionals — Frontiers in Oncology (October 2025)
Summary
As treatments for multiple myeloma improve, patients are living longer, making quality of life (QOL) an increasingly important part of care. However, the QOL questionnaires (QOLQs) currently used were mostly developed over 20 years ago and may not reflect the experiences of today’s patients.
What is the purpose of the study?
This study surveyed 224 myeloma patients and 48 healthcare professionals (HCPs) to assess how relevant the questions in 9 commonly used QOLQs are today. It found a large gap between what patients and HCPs consider important.
What were the findings of the study?
While HCPs found nearly all items relevant, patients only rated 26% of them as meaningful, mostly focusing on fatigue, pain, infections, and physical and social wellbeing.
The older questionnaires were created when treatment was mainly chemotherapy. Today’s therapies, such as immunotherapy, CAR T-cell therapy, and continuous treatment regimens, have different side effects and challenges that are not well captured by outdated tools.
Although newer tools (like MyPOS and HM-PRO) exist and include more relevant questions—such as those about sexual health, trust in the care team, and information needs—they are rarely used in practice.
Why this study matters
This study highlights the urgent need for updated QOL questionnaires that reflect the realities of modern myeloma treatments. Doing so will help doctors better understand what matters most to patients and improve care decisions.
Reference:
Lecat CSY, Bristogiannis S, Mehta D, Lwin Y, Land J, McCourt O, Dowling E, Correia N, Rabin NK, Xu K, Sive J, Papanikolaou X, Popat R, Lee L, McMillan A, Boyle EM, Yong K, Kyriakou C. Current quality of life questionnaires are not relevant for assessing QOL issues in multiple myeloma patients in the era of modern therapies: results from a survey with myeloma patients and myeloma healthcare professionals. Front Oncol. 2025 Oct 1;15:1656912. doi: 10.3389/fonc.2025.1656912.
Continuous or fixed carfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life survey from European myeloma network (emn) Italy — Annals of Hematology (October 2025)
Background
The KRd regimen (carfilzomib, lenalidomide, dexamethasone) is approved in Italy for treating relapsed/refractory multiple myeloma (RRMM) based on the ASPIRE trial. In that trial, carfilzomib was given for 18 cycles, followed by ongoing treatment with lenalidomide and dexamethasone (Rd). However, in Italian clinical practice, some doctors continue KRd beyond 18 cycles—this is known as continuous KRd (cKRd).
What is the purpose of the study?
To compare the safety and effectiveness of standard KRd (18 cycles) vs. continuous KRd using real-world data from 356 patients treated in 20 Italian centers.
Key findings
• Overall response rate (ORR) was 83%, with 35% achieving complete response, similar to results from the ASPIRE trial.
• Median overall survival (OS) was 62.9 months, longer than ASPIRE’s 48.3 months—possibly due to newer treatment options available today.
• No major increase in severe side effects was observed with longer use of KRd.
◦ Most common side effects were mild diarrhea and nerve-related symptoms (like tingling in hands), mainly from lenalidomide.
• Continuing KRd beyond 18 cycles did not significantly improve survival, especially in general patients.
• However, some benefits were seen in patients with more aggressive disease, suggesting cKRd might help certain high-risk individuals.
Conclusion
• The KRd regimen is safe and effective in the real-world setting, especially as a second-line treatment.
• Continuing carfilzomib beyond 18 cycles is generally safe, but does not clearly improve outcomes overall.
• It may benefit patients with aggressive disease, but more studies are needed to confirm this.
Reference:
Conticello, C., Fabro, V.D., Romano, A. et al. Continuous or fixedcarfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life surveyfrom European myeloma network (emn) Italy. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06602-9
Genomics Define Malignant Transformation in Myeloma Precursor Conditions — Journal of Clinical Oncology (October 2025)
Background
Multiple myeloma (MM) is always preceded by earlier, non-cancerous conditions: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these conditions do not cause symptoms, they can progress to MM over time. So far, doctors have only been able to diagnose MM once it causes organ damage.
What is the purpose of the study?
This study looked at whether genomic (DNA-based) testing could predict which MGUS and SMM patients are at high risk of developing MM, even before symptoms appear.
Key findings
• Researchers studied the genetic profiles of 374 patients with MGUS or SMM.
• They discovered two biologically different groups:
1. Genomic myeloma – patients whose cells already show cancer-like DNA changes, even if they don't yet have symptoms. These patients have a high risk of progressing to myeloma.
2. Genomic MGUS – patients whose DNA shows no signs of malignancy and are unlikely to progress to myeloma.
• Most SMM patients already have genomic myeloma, meaning their condition is biologically cancerous even without symptoms.
• In contrast, about 60% of MGUS patients showed no genetic signs of cancer and remained stable with no progression during follow-up.
Why this study matters
Using this genomic approach helps doctors better predict who will progress to active myeloma and who won’t. It could:
• Prevent unnecessary treatment in low-risk patients.
• Allow earlier intervention for high-risk patients.
• Improve how we classify and monitor these early conditions.
Implications for treatment
• Some patients with genomic myeloma remain stable for years, possibly due to the immune system keeping the disease under control.
• New treatments that work with the immune system may help maintain this stability.
• On the other hand, some patients with high-risk genomic changes may need more aggressive treatment earlier—even if they don’t yet have symptoms.
Important considerations
• Genomic testing alone is not enough to decide who should be treated right away.
• The best approach is to combine genomic testing with traditional clinical risk models like IMWG 2/20/20.
• This combined model (called "genomic IMWG 2/20/20") can help identify:
◦ Patients at high risk who may benefit from early treatment,
◦ And those at low risk who may avoid unnecessary therapy.
Limitations
• Some patients in the study had more advanced disease due to being seen at large cancer centers, so results may not fully reflect the general population.
• Genomic testing doesn’t yet detect all possible cancer-related changes.
• More research is needed to understand how genetics and the immune system interact in these early disease stages.
Conclusion
This study introduces a new way of understanding MGUS and SMM by using genetic testing to sort patients into:
• Genomic MGUS – stable and likely safe to monitor.
• Genomic myeloma – at real risk of progressing to cancer.
Combining genetics with traditional risk tools will help personalize care, identify who needs treatment sooner, and avoid overtreatment in those who don’t. This could lead to more personalized care and better outcomes.
Reference:
Francesco Maura et al. Genomics Define Malignant Transformation in Myeloma Precursor Conditions. J Clin Oncol 0, JCO-25-01733 DOI:10.1200/JCO-25-01733
Predictors of Delayed Responses to Teclistamab in Multiple Myeloma After Initial Non-Response — American Journal of Hematology (October 2025)
Background
In myeloma treatment, the drug teclistamab (a BCMA-targeting bispecific antibody) is usually assessed for effectiveness about 30 days after starting. At this point, doctors check if the patient has had a meaningful response to the drug. However, some patients may not show improvement by Day 30 (D30), and doctors face a difficult decision: continue treatment and risk side effects or stop and switch to something else.
What is the purpose of the study?
This study looked at 351 patients from a real-world U.S. database to better understand what happens to those who don’t respond by D30:
• 55% of patients (193 people) had no response (less than a "partial response") at D30.
• Of these, 23% (45 patients) eventually responded by Day 90 (a “delayed response”), while others either remained non-responders or passed away.
Key findings
1. Two main factors predicted delayed response:
◦ Having a "minimal response" (MR) at D30 (just below a partial response).
◦ Having a higher absolute lymphocyte count (ALC) at D30, a marker of immune system health.
2. Patients with progressive disease (PD) at D30 almost never improved later.
3. Patients with stable disease (SD) at D30 had a better chance of improvement if their ALC was not low.
4. Overall survival outcomes were similar for patients with delayed responses compared to those who responded early.
What this means for patients
• If you haven't had a clear response by Day 30, you may still benefit from continuing teclistamab, especially if you had a minimal response, or your immune system (ALC) looks strong.
• However, if your disease is clearly progressing at D30, continuing teclistamab is less likely to help.
• Simple blood tests like ALC may help guide decisions about whether to continue the drug.
Why this study matters
Teclistamab can cause serious side effects and is expensive, so doctors need tools to decide who should stay on it after early signs of non-response. This study helps provide those tools and shows that some patients do improve with more time.
Reference:
R. Banerjee, G. Kaur, B. M. Razzo, et al., “Predictors of Delayed Responses to Teclistamab in Multiple Myeloma After Initial Non-Response,” American Journal of Hematology (2025): 1–5, https://doi.org/10.1002/ajh.70108.
Joint modeling of progression-free survival and patient-reported outcomes to evaluate the association between disease progression and symptoms among patients with relapsed/refractory multiple myeloma — Journal of Patient-Reported Outcomes (October 2025)
What is the purpose of the study?
This study looked at whether worsening symptoms (specifically pain and fatigue) are linked to disease worsening or death in people with relapsed/refractory multiple myeloma (RRMM). These symptoms were measured using patient questionnaires from seven clinical trials.
Key findings
• Patients who reported increasing pain or fatigue were more likely to experience disease progression or death.
• This pattern was consistent across different types of treatments, including:
◦ Ongoing treatments (like immunotherapy or chemotherapy)
◦ One-time treatments like CAR T-cell therapy
• The stronger the symptom worsens, the higher the risk of the disease worsening.
Why these findings matter
• This study shows how patients feel (especially their levels of pain and fatigue) may be an indication of how their disease is progressing.
• It highlights the value of including patient-reported symptoms in treatment decisions and trial assessments—not just lab results or scans.
Strengths
• Used detailed data from individual patients, not just summary data.
• Included a wide range of patients with varying disease stages and treatments.
• Applied advanced statistical methods to link symptoms with outcomes.
Limitations
• Only included trials from one company (Celgene/BMS), so findings might not apply to all patients or studies.
• Some trials had limited symptom tracking after the disease worsened.
• Patients needed to have completed symptom surveys to be included, which could exclude some people.
What’s next?
• Future studies could explore how big a change in symptoms matters most (e.g., a 10- or 15-point increase in pain).
• Better symptom tracking after disease progression is needed.
• The study's method could be used in other cancers to better understand the link between symptoms and outcomes.
Conclusion
For patients with RRMM, worsening pain and fatigue may be early signs that the disease is getting worse. These symptoms should be taken seriously in both clinical care and research. Combining symptom tracking with standard medical tests can offer a more complete view of how treatments work.
Reference:
Knop, S., Einsele, H., Dhanda, D. et al. Joint modeling of progression-free survival and patient-reported outcomes to evaluate the association between disease progression and symptoms among patients with relapsed/refractory multiple myeloma. J Patient Rep Outcomes 9, 118 (2025). https://doi.org/10.1186/s41687-025-00943-9
Clinical Trials
Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study — Blood (September 2025)
What is the purpose of the study?
This study tested a new immune-based combination treatment — talquetamab plus daratumumab — for people with relapsed or refractory multiple myeloma (RRMM).
• 65 RRMM patients
• Most had received a median of 5 prior treatments
• Over 60% had triple-class refractory disease (resistant to the 3 main types of myeloma drugs)
• About 25% had already received bispecific antibody therapy
What was the treatment?
Patients received:
• Talquetamab: a bispecific antibody that targets a myeloma protein called GPRC5D
• Daratumumab: an antibody that helps the immune system kill cancer cells
They were given:
• Talquetamab weekly (QW) or every other week (Q2W)
• Daratumumab at its approved dose and schedule
Key findings
• Response rates:
◦ 71.4% (weekly group)
◦ 82.4% (every-other-week group)
• Progression-Free Survival (PFS): About 21–23 months in both groups — a strong result for heavily pretreated patients
• Side effects:
◦ Mostly mouth and skin issues, cytokine release syndrome, and infections
◦ Serious side effects (Grade 3 or 4) happened in about 82%, similar to what is seen with each drug alone
Why this study matters
• This combination shows promising effectiveness in patients who have run out of other options.
• It may provide longer-lasting responses than using either drug alone.
• Safety was manageable and consistent with what’s already known about each drug.
For patients with difficult-to-treat multiple myeloma, the combination of talquetamab and daratumumab shows strong potential to control the disease, even in those who have had many prior treatments. It may offer a new option in the future for those with limited choices.
Reference:
Ajai Chari, Niels W.C.J. van de Donk, Bhagirathbhai Dholaria, Katja C Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Tom G Martin, Daniel Morillo, Donna Reece, Paula Rodriguez-Otero, Manisha Bhutani, Anita D'Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Deeksha Vishwamitra, Sheri Skerget, Raluca I. Verona, Kalpana K Bakshi, Lijuan Kang, Thomas J Prior, Lien Vandenberk, Jaszianne Tolbert, Sangmin Lee, Damiette Smit, Ralph Wäsch; Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood 2025; blood.2025029360. doi: https://doi.org/10.1182/blood.2025029360
The impact of reduced dosing frequency of elranatamab on patient-reported outcomes in patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-3 — HemaSphere (September 2025)
Background
Multiple myeloma can cause symptoms such as bone pain, anemia (low red blood cells), kidney problems, and high calcium levels. Because it’s a long-term condition with ongoing symptoms and treatment side effects, it’s important to monitor patients’ quality of life using tools called patient-reported outcomes (PROs).
Elranatamab is a type of immunotherapy (a bispecific antibody) that helps the immune system target and kill myeloma cells. In the MagnetisMM-3 clinical trial, this treatment showed positive results in patients whose cancer had returned or didn’t respond to previous treatments. Patients also reported feeling less pain and an improved outlook on their future.
First, elranatamab is given once a week (QW). Patients who responded well after six treatment cycles could switch to a once every two weeks (Q2W) schedule, which is more convenient.
Key findings of the analysis
This analysis looked at whether switching to Q2W dosing affected patients’ quality of life. The results showed that:
• Most patients maintained a stable quality of life for over a year after switching to Q2W.
• Pain, fatigue, disease symptoms, and side effects remained stable or improved slightly in most patients.
• The less frequent dosing reduced the number of clinic visits, helping patients spend less time managing their treatment.
• These results were similar in patients whether or not they had previous treatment targeting a specific protein (BCMA).
Summary and conclusion
Switching to every-two-week elranatamab dosing did not negatively impact quality of life. Most patients continued to feel the same or better after the switch, while also benefiting from fewer clinic visits. This supports Q2W elranatamab as a convenient and effective option for treating relapsed or hard-to-treat multiple myeloma.
Reference:
Bahlis, N.J., Nooka, A.K., DiBonaventura, M., Sullivan, S.T., Chaudhary, M.A., Aydin, D. and Mohty, M. (2025), The impact of reduced dosing frequency of elranatamab on patient-reported outcomes in patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-3. HemaSphere, 9: e70224. https://doi.org/10.1002/hem3.70224
Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial — Blood (September 2025)
Summary
A study linked to the CASSIOPEIA trial looked at how well certain tests can predict outcomes in people with newly diagnosed multiple myeloma (NDMM) who received daratumumab-based treatment.
Key findings
• Patients who had no signs of cancer on PET/CT scans before maintenance therapy (pre-maintenance or PM PET-negative) had better outcomes, including longer progression-free survival (PFS) and a trend toward longer overall survival (OS).
• Patients who were negative on both PET/CT and bone marrow tests (minimal residual disease or MRD by MFC) had the best outcomes.
• In those treated with daratumumab, being PET-negative before maintenance was linked to significantly longer PFS and OS.
Why this study matters
Testing with PET/CT scans and bone marrow MRD can help predict how well patients with multiple myeloma will do after treatment. Achieving negativity on both tests after initial treatment, especially with daratumumab, is a strong sign of a better prognosis.
Reference:
Françoise Kraeber-Bodere, Bastien Jamet, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clement Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Philippe Moreau, Thomas Carlier, Cyrille Touzeau; Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial. Blood 2025; blood.2025030084. doi: https://doi.org/10.1182/blood.2025030084
Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma — Experimental Hematology and Oncology (September 2025)
Background
Zevorcabtagene autoleucel (zevor-cel) is a CAR T-cell therapy that targets a protein called B-cell maturation antigen (BCMA), a protein found on multiple myeloma cells. It uses a patient’s own immune cells, modified to attack cancer. It was approved in China in 2024 for patients with relapsed/refractory multiple myeloma (RRMM).
Study overview: LUMMICAR-1 Trial
• Type: Phase 2 clinical trial (no comparison group)
• Patients: 102 adults with RRMM in China
• Treatment: Zevor-cel after chemotherapy to prepare the body
• Main goals: Measure response to treatment and monitor safety
Key results
• Response rate:
◦ 92.2% of patients responded to treatment
◦ 71.6% had a complete or near-complete response
• Durability:
◦ At 18 months, 62.4% of patients had no disease progression
◦ Overall survival at 12, 18, and 30 months were 90.2%, 83.3%, and 79.4%, respectively
• Safety:
◦ Cytokine release syndrome (CRS), a common side effect, occurred in 90%, but was mostly mild
◦ Neurological side effects were rare (only 2 cases of mild symptoms)
◦ Serious side effects were uncommon and usually resolved
◦ Only one treatment-related death (due to pneumonia months after treatment)
How zevor-cel compares to other CAR T therapies
• Zevor-cel's effectiveness is similar or better than some other approved therapies like ide-cel and cilta-cel
• Fewer serious side effects were seen compared to some other CAR T therapies
• The use of a fully human design and gentler pre-treatment chemotherapy may contribute to better safety
Why this study matters
Zevor-cel could be a powerful and safer treatment option for patients in China and beyond, especially those who have had many previous treatments and have limited options left.
Limitations of the study
• The study had no comparison group
• More research is needed to confirm long-term safety and effectiveness
• Larger, international studies are underway
Conclusion
Zevor-cel shows strong and lasting responses in RRMM patients, with a manageable safety profile — making it a promising treatment option.
Reference:
Chen, W., Fu, C., Fang, B. et al. Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma. Exp Hematol Oncol 14, 119 (2025). https://doi.org/10.1186/s40164-025-00710-y
Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial — The Lancet Oncology (October 2025)
What is the purpose of the study?
Older patients with frailty and newly diagnosed multiple myeloma often have worse outcomes due to side effects and difficulty completing treatment. This study looked at whether a dexamethasone-sparing treatment (less steroid use) using lenalidomide and daratumumab could work better and be safer than the traditional treatment of lenalidomide with long-term dexamethasone.
How was the study conducted?
• 295 frail patients, average age 81, were enrolled across multiple centers.
• Patients were randomly split into two groups:
◦ Dexamethasone-sparing group: lenalidomide + daratumumab (with dexamethasone used only in the first 2 cycles)
◦ Control group: lenalidomide + full-course dexamethasone
• Researchers tracked how long patients lived without cancer worsening (progression-free survival) and how safe each treatment was.
Key results
• Longer time without disease worsening in the dexamethasone-sparing group: 53.4 months vs. 22.5 months in the control group.
• Fewer serious infections and similar death rates between both groups.
• Patients tolerated the dexamethasone-sparing treatment well, despite being older and frail.
Why this study matters
• Using less dexamethasone and adding daratumumab gave better outcomes without increasing side effects.
• This is the first large trial specifically designed for frail older adults with this type of cancer.
• The findings support changing clinical practices to reduce steroid use in frail patients.
For older, frail patients with newly diagnosed multiple myeloma, a treatment of lenalidomide plus daratumumab with limited steroid use offers better outcomes and should be considered a new standard option.
Reference:
Manier, Salomon et al. Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial. The Lancet Oncology, Volume 26, Issue 10, 1323 - 1333. October 2025. doi: 10.1016/S1470-2045(25)00280-3.
Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma — Cancer Medicine (October 2025)
Background
Cytokine Release Syndrome (CRS) is a common side effect of certain immune therapies for cancer, including talquetamab, a new treatment for relapsed/refractory multiple myeloma (RRMM). CRS happens when the immune system becomes overactive in response to treatment.
What is the purpose of the study?
This study looked at how often CRS occurs with talquetamab, how severe it is, and how to manage it safely.
Key findings
• CRS is common but usually mild. About 75% of patients experienced CRS, mostly mild to moderate (grade 1 or 2). Severe (grade 3) events were rare.
• Timing matters. CRS usually occurred early—within the first day of treatment—and lasted around 17 hours.
• Tocilizumab helps manage CRS. This medication, used to treat inflammation, reduced the chances of repeat CRS without affecting how well talquetamab worked against the cancer.
• Restarting treatment is usually safe. If there’s a break in treatment (up to 63 days), restarting talquetamab at full dose rarely caused CRS again.
• Similar to other therapies. CRS with talquetamab was very similar to what is seen with another drug called teclistamab, so doctors can use similar safety measures.
• Monitoring is key. Most CRS events occurred during early “step-up” doses, so close monitoring during these first treatments is important.
What this means for patients
• Talquetamab is an effective treatment option for multiple myeloma.
• While CRS is a common side effect, it’s usually mild and manageable.
• Early monitoring and treatments like tocilizumab help reduce risks.
• Doctors are gaining more experience and confidence using talquetamab safely.
Reference:
N. W. C. J. van de Donk, A. Chari, T. Martin, et al., “Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma,” Cancer Medicine 14, no. 19 (2025): e71276, https://doi.org/10.1002/cam4.71276.
Unique molecular assay (UMA): a next-generation sequencing targeted panel for efficient and comprehensive genomic profiling and risk stratification of multiple myeloma – Haematologica (October 2025)
What is the purpose of the study?
This study introduces a new genetic test called the unique molecular assay (UMA) panel, which helps doctors better understand the genetics of multiple myeloma. Knowing these genetic details is important to:
• Predict how aggressive the disease is
• Choose the most effective treatment
• Guide personalized care
What does the UMA panel do?
The UMA panel is a targeted DNA test that looks for key genetic changes in multiple myeloma, including:
• Gene mutations (like TP53)
• Chromosome changes (extra or missing parts)
• Translocations (rearrangements in specific genes)
It analyzes 82 important genes and uses modern DNA sequencing technology to give a complete picture of a patient’s cancer.
How was the UMA panel tested?
• Used on 150 patient samples
• Compared to standard tests (like FISH) in two separate labs
• Showed over 93% accuracy, matching or exceeding traditional methods
• Worked reliably in different hospitals, making it trustworthy and scalable
Why this study matters for patients
• More accurate diagnosis: Finds risk factors that standard tests might miss
• Better treatment planning: Helps doctors tailor therapy based on your cancer’s genetics
• Faster results and lower costs than some traditional methods
• Supports future treatments, like personalized immunotherapy
The UMA panel may soon become a regular part of testing for people with multiple myeloma or even earlier stages like smoldering myeloma. It could help:
• Detect high-risk patients sooner
• Guide when to start treatment
• Adapt as new genetic markers or therapies emerge
The UMA panel is a powerful, accurate, and affordable new genetic test that helps doctors better understand and treat multiple myeloma. It brings us closer to personalized cancer care, ensuring the right treatment for the right patient at the right time.
Reference:
Poletti A, Taurisano B, Mazzocchetti G, Lionetti M, Martello M, Vuong VM, Solli V, Marzocchi G, Maeda A, Vigliotta I, Borsi E, Armuzzi S, Pistis I, Marella A, Fabris S, Tacchetti P, Mancuso K, Rizzello I, Pantani L, Testoni N, Cavo M, Zamagni E, Bolli N, Terragna C. Unique molecular assay (UMA): a next-generation sequencing targeted panel for efficient and comprehensive genomic profiling and risk stratification of multiple myeloma. Haematologica 2025;110(10):2436-2450; https://doi.org/10.3324/haematol.2025.287559.
Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003) — Blood Cancer Journal (October 2025)
Summary
A new phase III study by the Asian Myeloma Network (AMN) found that adding the affordable chemotherapy drug Cytoxan® (cyclophosphamide) to the standard treatment of Pomalyst® (pomalidomide) and dexamethasone (PD) significantly improved outcomes for patients with relapsed or refractory multiple myeloma (RRMM).
The study, known as AMN003, enrolled 122 patients across five Asian countries who had already been treated with Revlimid® (lenalidomide) and a proteasome inhibitor such as Velcade® (bortezomib). Patients who received the three-drug combination (PCD) had a median progression-free survival (PFS) of 10.9 months, nearly double that of those treated with PD alone (5.8 months). The overall response rate (ORR) was also higher with PCD—61% compared to 38%. These improvements were achieved without more serious side effects.
What this means
The PCD regimen (pomalidomide, cyclophosphamide, and dexamethasone) offers a safer, more effective, and affordable option for people with relapsed or refractory myeloma. Side effects were manageable and similar to those seen with standard treatment. This makes PCD a strong alternative for patients who have already received multiple lines of therapy and are looking for new treatment options that balance efficacy, safety, and cost.
Why this study matters
Access to advanced therapies like CAR T-cell treatment and bispecific antibodies remains limited and expensive in many parts of Asia and other regions worldwide. The results of the AMN003 study show that an accessible, oral, and low-cost combination can still deliver meaningful clinical benefits. By improving survival without adding toxicity or financial burden, the PCD regimen could become a new standard treatment for relapsed myeloma patients, helping to close the global gap in cancer care access.
Reference:
Kim, J.S., Song, Y., Jen, WY. et al. Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003). Blood Cancer J. 15, 155 (2025). https://doi.org/10.1038/s41408-025-01356-z
Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies? — Journal of Cancer Research and Clinical Oncology (October 2025)
Background
Multiple myeloma remains incurable. Even with newer treatments, most patients eventually relapse and need further therapies. Some become resistant to standard treatments — this is known as triple-class refractory (TCR) multiple myeloma, which is especially hard to treat.
What is melflufen?
Melflufen is a chemotherapy-based drug derived from melphalan. It was combined with dexamethasone (a steroid) and tested in clinical trials for patients with TCR myeloma who had received 3 or more previous treatments. Although it showed some benefit, it was withdrawn in the U.S. because it did not improve overall survival compared to another treatment.
However, it is still approved in Europe for certain patients, especially:
• Those who have not had a stem cell transplant (ASCT), or
• Those whose disease came back more than 3 years after ASCT.
Key findings
• The paper describes three patients treated with melflufen-dexamethasone in clinical trials who had exceptionally long-lasting responses and good tolerance.
• Most patients in these studies had shorter benefit, but these cases show that some may still respond very well.
Newer treatments
• New immunotherapies (CAR T-cells and bispecific antibodies targeting BCMA or GPRC5D) have shown stronger and more durable results than melflufen in general.
• These include drugs like ide-cel, cilta-cel, teclistamab, and others, which have become standard options for many patients with advanced myeloma.
Challenges with new therapies
• These new treatments can cause serious side effects, such as infections, immune reactions, and low blood counts.
• They are also expensive and may not be available or suitable for all patients, especially those who are older or have other health issues.
Why melflufen still matters
• Melflufen may be a safer, easier-to-use option for patients who can't get or tolerate newer immunotherapies.
• It may also be useful between treatments, after immunotherapy fails, or in countries with limited access to the newest drugs.
• Side effects are mostly blood-related and can often be managed with supportive care.
• It may also help maintain quality of life for patients responding to the drug.
Conclusion
Melflufen-dexamethasone is not as powerful as the latest immunotherapies, but for certain patients, especially those who are older, frail, or not eligible for newer options, it may still offer a meaningful treatment choice.
Reference:
Talarico, M., Barbato, S., Maisnar, V. et al. Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies? J Cancer Res Clin Oncol 151, 288 (2025). https://doi.org/10.1007/s00432-025-06326-3
High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial—Blood (October 2025, Plenary Paper)
What are the key findings of this plenary paper?
• Using VRD (bortezomib, lenalidomide, dexamethasone) with stem cell transplant led to very long survival:
◦ Progression-free survival (PFS): 78 months
◦ 9-year overall survival: 66% — the best reported for a triplet therapy.
BUMEL vs MEL200 (Transplant conditioning regimens)
• Patients who had BUMEL (busulfan + melphalan) before transplant did better overall than those who had MEL200 (melphalan alone), especially:
◦ In patients with advanced-stage disease (ISS stage II or III)
◦ And those with high-risk genetic features (e.g., t(14;16) or del(1p))
• In contrast, MEL200 worked well in patients with early-stage disease (ISS stage I) and del(17p).
MRD negativity and survival
• More patients receiving BUMEL achieved deep remission (MRD-negative: 68% vs. 58%).
• Median PFS:
◦ BUMEL: 89 months
◦ MEL200: 73.1 months
Safety
No major safety concerns were found with either approach.
Why this plenary paper matters
For patients newly diagnosed with multiple myeloma and eligible for stem cell transplant, intensive VRD treatment plus BUMEL conditioning offers some of the longest survival outcomes reported, especially in more advanced disease.
Reference:
Juan José Lahuerta, Jesús San-Miguel, Ana Jiménez-Ubieto, Rafael Alonso, Bruno Paiva, Noemí Puig, M. Teresa Cedena, Norma Carmen Gutierrez, María José Calasanz, Manuela Fernández Guijarro, Rafael Ríos Tamayo, Albert Oriol Rocafiguera, María Jesús Blanchard, Estrella Carrillo Cruz, Rafael Martínez-Martínez, Joan Bargay, Ana Sureda Balari, Javier de la Rubia, Miguel Teodoro Hernández García, Valentín Cabañas, Felipe Casado Montero, Luis Palomera Bernal, Yolanda González Montes, Joaquín Martínez-Lopez, Paula Rodriguez-Otero, Isabel Krisnik, José M. Arguiñano, María Esther Gonzalez García, Enrique M. Ocio, Javier de la Cruz, María Victoria Mateos, Laura Rosiñol, Joan Bladé; on behalf of the Spanish Myeloma Group , High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial. Blood 2025; 146 (15): 1747–1758. doi: https://doi.org/10.1182/blood.2025028313
Machine learning risk stratification strategy for multiple myeloma: Insights from the EMN–HARMONY Alliance platform — Hemasphere (October 2025)
Background
Doctors traditionally assess the risk of multiple myeloma using clinical staging systems like ISS and R-ISS, which group patients based on blood test results and certain genetic abnormalities. However, these tools don't always predict how a patient’s disease will progress with high accuracy.
What is the purpose of the study?
This study used machine learning (ML) to develop more accurate, personalized risk prediction models for people newly diagnosed with multiple myeloma (NDMM). Researchers analyzed data from over 14,000 patients, including more than 10,000 newly diagnosed patients, to build three models:
1. A comprehensive model using 20 clinical and genetic factors.
2. A simplified model using just 6 key factors (age, hemoglobin, albumin, β2-microglobulin, 1q gain, and 17p deletion).
3. A cytogenetics-free model, designed for use where genetic testing is not available.
Results of the study
All models outperformed the existing ISS, R-ISS, and R2-ISS systems in predicting both overall survival and progression-free survival. Notably, the simpler models still performed well, making them useful in real-world settings, including places with limited access to advanced testing.
The models were also tested in various patient groups, including those with advanced or relapsed disease and those treated with modern drugs like daratumumab, confirming their broad usefulness.
Why this study matters
Importantly, this approach includes a dynamic risk score that updates based on how well a patient responds to treatment—offering a more personalized and adaptable way to monitor risk.
A major strength of this tool is its online availability. Doctors can access it through a free calculator to get real-time, individualized risk estimates based on each patient’s specific data.
In the future, adding even more biological data—like MRD (minimal residual disease), gene mutations, and imaging results—could further improve this system’s accuracy.
Reference:
Mosquera Orgueira, A., Gonzalez Perez, M.S., D'Agostino, M., Cairns, D.A., Larocca, A., Palacios, J.J.L., Wester, R., Bertsch, U., Waage, A., Zamagni, E., Pérez Míguez, C., Rojas Martínez, J.A., Mai, E.K., Crucitti, D., Salwender, H., Dall'Olio, D., Castellani, G., Piñeiro Fiel, M., Bringhen, S., Zweegman, S., Cavo, M., Iqbal, S., Hernandez Rivas, J.M., Bruno, B., Cook, G., Kaiser, M.F., Goldschmidt, H., Van De Donk, N.W.C.J., Jackson, G., San-Miguel, J.F., Boccadoro, M., Mateos, M.-V. and Sonneveld, P. (2025), Machine learning risk stratification strategy for multiple myeloma: Insights from the EMN–HARMONY Alliance platform. HemaSphere, 9: e70228. https://doi.org/10.1002/hem3.70228
GPRC5D-targeted CAR T-cell therapy (CT071) in patients with relapsed or refractory multiple myeloma: a first-in-human, single-centre, single-arm, phase 1 trial — The Lancet Haematology (October 2025)
What is the purpose of the study?
Multiple myeloma often returns or becomes resistant to treatment. CT071 is a new type of personalized cell therapy (CAR T-cell therapy) that targets a specific protein (GPRC5D) found in myeloma cells.
This study tested how safe and effective CT071 is for people whose cancer has come back or no longer responds to standard treatments.
How was the study conducted?
• Conducted in China with 20 patients who had tried at least three previous treatments.
• Patients were given one of two doses of CT071.
• Researchers mainly looked at safety but also checked how well the therapy worked.
Results:
• No major safety issues were found, and the lower dose was chosen for future studies.
• All patients experienced some blood-related side effects.
• 60% had mild to moderate immune reactions (cytokine release syndrome).
• One patient (5%) had a serious but manageable neurological side effect.
• 100% of patients responded to the treatment, and half had a complete or better response.
• No deaths related to the treatment occurred.
Why this study matters
CT071 appears to be safe and highly effective for patients with difficult-to-treat multiple myeloma, showing promising results for future use.
Reference:
Jin L, Gu S, Ruan Q, Lu J, Qiang W, He H, Fan X, Liu J, Guo P, Meng X, Rajakumaraswamy N, Chen D, Li Z, Du J. GPRC5D-targeted CAR T-cell therapy (CT071) in patients with relapsed or refractory multiple myeloma: a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Haematol. 2025 Oct;12(10):e798-e807. doi: 10.1016/S2352-3026(25)00176-0.
Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models — Blood (October 2025)
What is the purpose of the study?
Ramantamig (JNJ-79635322) is a new experimental treatment that is being studied for multiple myeloma. It is a trispecific antibody, meaning it can attach to three different targets at once:
• CD3 on T cells (a type of immune cell),
• BCMA, and
• GPRC5D, both commonly found in myeloma cancer cells.
Why this study matters
By binding to both BCMA and GPRC5D on cancer cells, ramantamig increases its ability to stick to tumors and helps the immune system kill cancer cells more effectively, even when the cancer cells vary (tumor heterogeneity) or try to escape detection.
In lab tests and animal studies, ramantamig:
• Activated T cells to kill both single- and dual-target-expressing myeloma cells.
• Reduced cancer cells in patient samples and animal models.
• Showed strong antitumor effects, suggesting it could help prevent relapse and improve treatment response.
Looking ahead
Clinical trials are currently ongoing to test ramantamig in patients with relapsed or refractory myeloma.
Reference:
Kodandaram Pillarisetti, Danlin Yang, Leopoldo Luistro, Jianhong Yao, Melissa Smith, Peter Vulfson, James Testa, Randolph Ponticiello, Scott R Brodeur, Bradley Heidrich, Kathryn Packman, Sanjaya Singh, Ricardo M Attar, Yusri A Elsayed, Ulrike Philippar; Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood 2025; blood.2025030027. doi: https://doi.org/10.1182/blood.2025030027
U.S. Food and Drug Administration (FDA)
FDA approves new label warning for Carvykti® (ciltacabtagene autoleucel) due to reports of immune-effector cell-associated enterocolitis following treatment; maintains that overall benefit still outweighs potential risk
On Friday, October 10, the U.S. Food and Drug Administration (FDA) approved changes to the labeling of Carvykti® (ciltacabtagene autoleucel) after receiving reports of a condition called immune effector cell-associated enterocolitis (IEC-EC) in some patients who received this CAR T-cell therapy.
According to the FDA, cases of IEC-EC were identified during clinical trials and from postmarketing safety reports. Symptoms included severe or long-lasting diarrhea, abdominal pain, and weight loss, sometimes requiring total parenteral nutrition (IV feeding). The condition may appear weeks to months after infusion. Some patients required immunosuppressive treatment, such as corticosteroids, in addition to supportive care. Rarely, serious complications, including intestinal perforation and sepsis, have resulted in death.
The FDA also updated Carvykti’s Clinical Studies section to include new overall survival (OS) data from the CARTITUDE-4 trial—a randomized, open-label, multicenter controlled study in adults with relapsed, lenalidomide-refractory multiple myeloma who received at least one prior line of therapy. After a median follow-up of 33.6 months, Carvykti showed a statistically significant improvement in overall survival compared to standard therapy.
FDA recommendations
• Patients or trial participants who develop IEC-EC should be managed following institutional guidelines and referred to gastroenterology and infectious disease specialists.
• If IEC-EC does not respond to treatment, doctors should evaluate for T-cell lymphoma of the gastrointestinal tract, which has been reported in rare postmarketing cases.
Despite these new warnings, the FDA states that the benefits of Carvykti continue to outweigh the risks, given its demonstrated survival benefits.
“Continuous monitoring and assessment of the safety of all biologics, including Carvykti, is an FDA priority, and we remain committed to informing the public when we learn new information about these products,” the FDA emphasized.
Reference:
“FDA Approves Labeling Changes that Include a Boxed Warning for Immune Effector Cell-associated Enterocolitis Following Treatment with Ciltacabtagene Autoleucel (CARVYKTI, Janssen Biotech, Inc.),” U.S. Food and Drug Administration Medical Product Safety Information, October 10, 2025.
FDA approves Blenrep® (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone as treatment for patients with relapsed/refractory multiple myeloma who have received at least two prior lines of therapy
On Thursday, October 23, the U.S. Food and Drug Administration (FDA) announced its approval of Blenrep® (belantamab mafodotin-blmf)— "a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate — with bortezomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent."
According to GSK, the approval is supported by data from the DREAMM-7 phase III trial. “In patients who had two or more prior lines of therapy (3L+), including a PI and an IMID, Blenrep in combination demonstrated a clinically meaningful 51% reduction in the risk of death [HR 0.49, 95% confidence interval (CI): 0.32-0.76] and a tripled median progression-free survival (PFS) of 31.3 months [95% CI: 23.5-NR)] versus 10.4 months [95% CI: 7.0-13.4] for a daratumumab-based triplet (DVd) [HR 0.31, 95% CI: 0.21-0.47]. The safety and tolerability profiles of the Blenrep combination were broadly consistent with the known profiles of the individual agents,” states GSK in a press release.
Due to the risk of ocular toxicity, Blenrep is only available through a Risk Evaluation and Mitigation Strategy (called BLENREP REMS).
"This updated REMS helps ensure safe and appropriate use of Blenrep while reducing paperwork and improving communication between healthcare providers and eye specialists," said GSK, which also offers an optional support program called Together with GSK for all U.S. patients prescribed with the drug.
Full prescribing information for Blenrep will be posted on Drugs@FDA which includes “a Boxed Warning or the risk of ocular toxicity, including corneal epithelium changes resulting in vision deterioration. Among those receiving belantamab mafodotin-blmf in DREAMM-7, ocular toxicity occurred in 92% of patients, including Grade 3 or 4 in 77%, with 83% requiring dosage modification due to ocular toxicity,” according to the FDA.
References:
• “FDA approves belantamab mafodotin-blmf for relapsed or refractory multiple myeloma,” U.S. Food and Drug Administration, Resources for Information, Approved Drugs, October 23, 2025.
• “Blenrep approved by US FDA for use in treatment of relapsed/refractory multiple myeloma,” GSK press release, October 23, 2025.
FDA grants fast track designation to HDP-101 (pamlecbart tismanitin) as treatment for multiple myeloma
On Thursday, October 23, Heidelberg Pharma AG announced via a press release that the U.S. Food and Drug Administration (FDA) has granted fast track designation to HDP-101 (pamlectabart tismanitin) for the treatment of multiple myeloma.
According to Heidelberg, this decision was supported by early laboratory and clinical data from an ongoing Phase I/IIa study evaluating the safety and antitumor activity of HDP-101 in patients with relapsed or refractory multiple myeloma.
The company noted that HDP-101 is still experimental and has not yet been approved by the FDA or any regulatory authorities. Its safety and effectiveness are still being studied.
Reference:
“Heidelberg Pharma’s Lead ADC Candidate HDP-101 Granted Fast Track Designation by US FDA for the Treatment of Multiple Myeloma,” Heidelberg Pharma press release, October 23, 2025.
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