IMS 2025 Highlights in Multiple Myeloma Treatment

The 22nd International Myeloma Society (IMS) Annual Meeting was held from September 17–20, 2025 in Toronto, Canada.

By Dr. Joseph Mikhael 
IMF Chief Medical Officer 
 

Scope and Methodology

This article was published in the Fall 2025 Edition (https://www.myeloma.org/resource-library/myeloma-today-fall-2025) of Myeloma Today and summarizes key multiple myeloma research highlights presented at the 22nd International Myeloma Society (IMS) Annual Meeting from September 17-20, 2025 in Toronto, Canada. Content was developed by the International Myeloma Foundation medical editorial team using official meeting abstracts, presentations, and related peer-reviewed publications available through September 2025. It is intended for patients, care partners, and oncology professionals and was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on December 3, 2025.

Key Takeaways

Smoldering myeloma:
    • Researchers are getting better at identifying which patients are “high-risk.”
    • A new drug, linvoseltamab, showed a 100% response rate in early testing.
    • Darzalex Faspro is now FDA-approved as the first treatment for high-risk smoldering myeloma.

Frontline therapy:
    • Four-drug combinations remain the standard.
    • Early studies adding new immune therapies (like teclistamab) show very strong responses but also higher infection risks.
    • Another new drug, iberdomide, combined with daratumumab, worked well and led to deep responses.

High-risk myeloma
    • New risk categories help doctors tailor treatment better.
    • Patients with several genetic abnormalities or a quick relapse after starting treatment may need more aggressive approaches.

Immunotherapy (CAR T & bispecifics):
    • Doctors are trying to figure out the best order to use these powerful therapies.
    • Tests that show whether your myeloma still has targets like BCMA or GPRC5D may soon help guide treatment choices.

Bridging therapy for CAR T:
    • Treatment between cell collection and infusion helps keep the disease under control.
    • This can reduce side effects and improve outcomes with CAR T-cell therapy.

Looking ahead:
    • New approaches include trispecific antibodies, dual CAR T-cell treatments, and using a new drug (cevostamab) after CAR T to help keep the cancer in remission.
 

The international myeloma community gathers annually for four days to review the latest research in myeloma and to facilitate discussion between world experts. With more than 3,000 attendees from over 70 countries, the 2025 International Myeloma Society (IMS) Annual Meeting was inordinately busy and productive. Below are just some areas of note, in research and discussion. 
 

Smoldering multiple myeloma 

Smoldering multiple myeloma (SMM) continues to be a very hot topic as we seek to define this condition more accurately. We are also working to determine the optimal time to intervene with treatment, and studying what specific treatment that might be. One fascinating abstract presented the preliminary results of using the novel bispecific antibody linvoseltamab (Lynozyfic™) as monotherapy for patients with high-risk smoldering myeloma (HRSMM). The response rate in the group of 20 study patients was 100%, and it appears to come with fewer side effects than when bispecific antibodies are given later in the disease course. [Update: Darzalex Faspro® (daratumumab and hyaluronidase-fihj) has been approved by the FDA on November 6, 2025 (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma), as the first-ever treatment for adult patients with HRSMM.] 

Frontline therapy 

Significant advances have been made in frontline therapy, the initial treatment given to a patient, with the introduction of quadruplet (4-drug) therapy for most patients. Several ongoing clinical trials are trying to answer the question: Can we improve on this? The MajesTEC-5 clinical trial is studying the bispecific antibody teclistamab (Tecvayli®) in frontline therapy prior to autologous stem cell transplant (ASCT) in several combinations, adding it to daratumumab (Darzalex®), bortezomib (Velcade®), lenalidomide (Revlimid®), and dexamethasone (DVRd). It is too early to make detailed conclusions, but the response rate was 100% and patients were able to have their stem cells collected in preparation for ASCT. However, infection rates were high, underscoring the importance of reducing the risks of infection in patients who are treated with bispecific antibodies. 
 
Another clinical trial evaluated the novel drug iberdomide, which is part of a new class of agents known as cereblon E3 ligase modulatory drugs (CELMoDs) that is not yet approved by the U.S. Food and Drug Administration (FDA) for use in myeloma but is being heavily studied in clinical trials, mostly in the relapsed/refractory multiple myeloma (RRMM) setting. This trial was the combination of iberdomide + daratumumab + dexamethasone in patients not proceeding to ASCT. This very potent combination therapy demonstrated a response rate of 95%, with more than 50% of study patients achieving minimal residual disease (MRD)-negativity. This may show both enhanced activity and tolerability of iberdomide in myeloma. 
 
 

High-risk multiple myeloma 

There is ongoing research on how to optimally treat patients who have high-risk multiple myeloma (HRMM). The new classification of HRMM by the IMF’s International Myeloma Working Group (IMWG) and IMS should facilitate more studies to help us identify more effective treatments. 
 
One important study presented at IMS 2025 was the GMMG-CONCEPT clinical trial from Germany, which investigated long-term therapy with the quadruplet combination of isatuximab (Sarclisa®), carfilzomib (Kyprolis®), lenalidomide, and dexamethasone (Isa-KRd) in ASCT-eligible (TE) and ASCT-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with HRMM for whom prospective clinical trials are limited, aiming to induce MRD-negativity. About 20% of patients with NDMM have high-risk disease, and patients with HRMM tend to relapse quickly after achieving remission. 
 
In the Summer 2025 edition (https://www.myeloma.org/resource-library/myeloma-today-summer-2025) of Myeloma Today, I reviewed how prolonged combination therapy seemed to improve outcomes in patients with HRMM. At IMS 2025, updated data were presented on different subgroups of patients with HRMM. Having more than one cytogenetic abnormality (CA), especially when one of the CAs is deletion 17p, portends an even shorter duration of remission. The concept of “double hit” or ultra-high-risk MM identifies a group of patients who really require a novel approach to therapy. 
 
At IMS 2025, we gained insight on how to define “functional high-risk” disease, when patients relapse within 18 months of starting frontline therapy. Many of these patients do not have the usual markers of HRMM but should be treated as high-risk as early relapse speaks to a more aggressive disease. 
 
 

Immunotherapies 

At present, one of the most important discussions among myeloma doctors is focused on optimizing the novel treatment approaches of CAR T-cell therapies and bispecific antibodies. As more immunotherapies enter the market, we seek to understand the best way to sequence them. Two areas of interest explored at IMS were cell function and targets on the myeloma cells. Both CAR T-cell therapies and bispecific antibodies depend on functioning T cells and yet, we do not have easy ways to assess T cell “health” and how they are impacted by the disease and other treatments. 
 
We also know that immunotherapies depend on the targets they adhere to on the myeloma cell — primarily B-cell maturation antigen (BCMA) and GPRC5D. Assays have been developed to test the presence of these targets after being treated with these therapies, and they may be able to guide us in our choice of the next therapy. For example, if someone has had a CAR T-cell therapy that targets BCMA and their disease then progresses, we can test their myeloma as to the expression of BCMA to know if another BCMA therapy is likely or unlikely to work. Having these tests in real time could help in treatment decisions, and the field is clearly moving to testing these prior to instituting treatments to optimize their use.  
 
 

To bridge or not to bridge? 

“Bridging” therapy is treatment given to patients after their T cells are collected for CAR T-cell therapy, but before those T cells are re-infused. It is important for many reasons. When a patient’s disease is well-controlled, they are less likely to experience some of the short-term side effects like cytokine release syndrome (CRS) and neurological toxicity.  
 
Furthermore, patients will have a better response to the therapy. Lastly, effective bridging therapy seems to reduce the risk of longer-term neurological toxicities like Parkinsonism. I expect to see more emphasis on bridging therapies, as we use more CAR T-cell therapy. 
 
 

Looking to the future 

It is exciting to see new therapies emerge from the constantly changing environment of myeloma research, and more are on the way! Trispecific antibody therapies are drugs that adhere to TWO targets on the myeloma cell to enhance their affinity to myeloma when they engage T cells to destroy myeloma cells.  
 
One fascinating study evaluated giving TWO separate CAR T-cell products — one BCMA-directed, the other GPRC5D-directed. While it is too early to measure the impact, this study demonstrated that it is feasible and may even further deepen response, as it may capture even more myeloma cells. 
 
Lastly, a protocol was presented with cevostamab — a bispecific antibody that has an entirely new target known as FcRH5 — immediately, after CAR T-cell therapy, in an effort to achieve a deep response with CAR T, then maintain it long-term with a bispecific antibody that has a different target. MRD testing will be used to guide the discontinuation of the cevostamab. 
 

 

About Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO

International Myeloma Foundation Chief Medical Officer
TGen, City of Hope Cancer Center—Phoenix, AZ, USA

Dr. Mikhael is a Professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope Cancer Center. He is also the Chief Medical Officer of the International Myeloma Foundation (IMF). He is a consultant hematologist and Director of Myeloma Research at the HonorHealth Research Institute where he conducts phase 1 clinical trials. He just completed a term as Councilor on the American Society of Hematology Executive. He also recently led the ASCO guidelines for multiple myeloma.   

Dr. Mikhael was recently a hematologist at Mayo Clinic Arizona where he served as a Professor at the Mayo College of Medicine, Associate Dean of Graduate Medical Education, and Deputy Director - Education of the Mayo Clinic Cancer Center. He has been recognized with numerous awards in education, including being in the Mayo Clinic Resident and Fellow Association Hall of Fame as Educator of the Year. He was also recently named in the Top 100 Doctors in the United States.  

Dr. Mikhael did his initial medical school training in Ottawa, Canada, followed by his Hematology Residency at Princess Margaret Hospital in Toronto. He then did a Multiple Myeloma Fellowship there along with a master’s degree in Education from the University of Toronto. He was on staff at PMH until being recruited to Mayo Clinic in 2008.  

He specializes clinically in plasma cell disorders, namely multiple myeloma, amyloidosis, and Waldenström's macroglobulinemia. Dr. Mikhael is currently the principal investigator of many clinical trials, primarily in multiple myeloma. His other clinical research interests also include pharmaco-economics, communication skills, and media relations. He has published more than 150 peer-reviewed articles in these fields. He lectures internationally on a regular basis, is an active member of the IMF’s International Myeloma Working Group (IMWG) and serves on the editorial board of the Journal of Clinical Oncology.   

Dr. Mikhael is leading the IMF’s M-Power Project, which seeks to improve the care of African Americans with myeloma. He also spends about twenty percent of his time in the developing world, seeking ways to enhance access to myeloma therapies in underprivileged countries.