Myeloma Research Updates: Key Takeaways from ASCO, EHA & IMWG

Every year, three annual events that take place in quick succession hold a special significance for the researchers and clinicians working in the field of myeloma. The 2025 annual meeting of the American Society of Clinical Oncology (ASCO), the largest gathering of cancer specialists in the world with 45,000 doctors attending, took place from May 30 through June 3 in Chicago, IL. The 2025 Summit of the IMF International Myeloma Working Group (IMWG), which brought together approximately 100 of the more than 360 global experts in myeloma, took place June 10-12 in Milan, Italy. The 2025 annual congress of the European Hematology Association (EHA) took place June 12-15, also in Milan, attracting 18,000 doctors from all areas of hematology. 

It is impossible to cover in detail all that transpired during these three important events in this blog. Yet, I aim to summarize for you the selected takeaways that hold the greatest impact for patients with myeloma. For more in-depth information, view our library of videos here (https://www.myeloma.org/imf-videos).

 

Key Takeaways

• ASCO, EHA, and IMWG together accelerated practice-changing insights across the myeloma continuum.
• Early detection/monitoring advances (e.g., iStopMM) refine SMM risk and inform earlier intervention.
• Frontline therapy: optimization of quadruplets and maintenance, with signals from PERSEUS and AQUILA for different fitness groups.
• High-risk disease: dedicated strategies (e.g., GMMG CONCEPT) highlight tailored regimens and risk-adapted care.
• Relapsed disease: sequencing refined by timing (early vs late) and integration of targeted/immunotherapies.
• BCMA space: CAR T durability and earlier-line movement; bispecifics/trispecifics expand off-the-shelf options.
• ADCs: belantamab mafodotin combos (DREAMM-7/-8) show renewed efficacy, redefining its role.
• MRD-guided decisions gain traction for maintenance duration and escalation/de-escalation strategies.

 

A Global Hub for Myeloma Research and Collaboration

Screening for myeloma 

The Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) clinical trial (https://www.myeloma.org/black-swan-research-initiative/istopmm) of early detection and prevention is a massive project that is educating us about the feasibility and usefulness of screening. Age, genetics, and family history have been shown to be important factors in all screening programs, and we should expect the same in myeloma, especially as it is twice as common in patients of African descent. In the next 2 years, the iStopMM  study will likely answer the key question of whether screening for myeloma saves lives, and we are all eager to see the data.

Smoldering multiple myeloma (SMM)

SMM is an asymptomatic precursor to active myeloma. Discussed at the IMWG Summit, the 20-2-20 model (https://www.myeloma.org/videos/high-risk-smoldering-multiple-myeloma)defines high-risk smoldering multiple myeloma (HR SMM) as having at least two of the following: 20% plasma cells in the bone marrow, monoclonal spike (M-spike) of at least 2 g/dL, and free light chain ratio of involved-to-uninvolved light chains being greater than 20. This model helps place SMM along the spectrum of myeloma, though definitions are still evolving. 

The AQUILA clinical trial (https://www.myeloma.org/videos/daratumumab-vs-active-monitoring-high-risk-smoldering-multiple-myeloma-aquila-study-results) presented at the annual meeting of the American Society of Hematology (ASH) in December 2024 compared early treatment with Darzalex® (daratumumab) to close observation of patients with HR SMM. After 5 years, 63% of treated patients had not progressed, while 40% in the observation group progressed to active myeloma. Monitoring had a median time to progression of around 3 years, which wasn’t yet reached in the treatment arm. 

The AQUILA study was critical to proving that we can delay the progression to active myeloma and even improve patient survival with 3 years of Darzalex. While early intervention may delay progression, it does not necessarily prevent active myeloma. Since there is no FDA-approved treatment for HR SMM, patients should consider clinical trials and discuss this with their doctors. Currently, enrollment is open for studies of drugs approved for active myeloma, as well as studies with curable intent. Ultimately, the best strategy combines the patient’s perspective with clear data to guide truly individualized care. 
 
There is consensus among experts that no clinical trials are needed for low-risk SMM. For intermediate-risk SMM, there is a need for studies of innovative approaches to intercepting the evolution to myeloma. Ongoing research to identify risk factors at baseline may move patients with HR SMM to an early myeloma category.

Translating Research into New Patient Treatments

Treatment of patients with newly diagnosed multiple myeloma (NDMM) was addressed in three key studies. 

The PERSEUS clinical trial (https://www.myeloma.org/videos/improved-depth-response-mrd-negativity-dara-vrd-transplant-eligible-ndmm-perseus-trial)has truly changed the way we treat NDMM by demonstrating that “triplet” (3-drug) combination therapies are less effective than “quadruplet” (4-drug) combinations in patients who are proceeding to autologous stem cell transplantation (ASCT). Specifically, this year’s data from ASCO and EHA showed that the combination of Darzalex and Velcade® (bortezomib), Revlimid® (lenalidomide), and dexamethasone [DVRd] plus ASCT and dual maintenance with Darzalex and Revlimid (D-R) resulted in extraordinary outcomes for patients. More than half of the DVRd patients attained minimal residual disease (https://www.myeloma.org/multiple-myeloma/tests-staging/mrd-mass-spectrometry-testing) (MRD)-negativity for more than 2 years. 

The MIDAS clinical trial (https://www.myeloma.org/videos/top-10-myeloma-breakthroughs-asco-eha-frontline-therapy-early-late-relapse-car-t-cell) studied the quadruplet therapy of Sarclisa® (isatuximab), Kyprolis® (carfilzomib), Revlimid, and dexamethasone [Isa-KRd]. After this quadruplet induction, patients who were MRD-negative received a less intense therapy than patients who were MRD-positive. It's too early for a final conclusion, but it’s clear that MRD will guide more therapy with time. In the interim, we're already seeing that patients who achieved MRD-negativity may not need ASCT at all, but we need more time to see if this MRD results holds up for progression-free survival (PFS) before we stop doing transplants for patients who achieve MRD negativity with induction. For patients who are MRD-positive, it appears that there is no more need of tandem transplants (two transplants in a row). We’re looking forward to the more mature data that will be reported from this clinical trial.

The GMMG-CONCEPT clinical trial (https://www.myeloma.org/videos/updated-interim-analysis-isatuximab-carfilzomib-dex-frontline-treatment-high-risk-myeloma) focused on patients with high-risk multiple myeloma (HRMM). About 20% of newly diagnosed patients have HRMM. Historically, it has been challenging to treat these patients as they tend to relapse quickly. The more intense 4-drug regimen of Isa-KRd, then ASCT, is followed with continuing the 4-drug therapy, but eventually dropping the steroid dexamethasone from the protocol and giving patients Isa-KR. The outcomes were much better than what we've previously seen with HRMM and may signify the benefit of a more intense therapy approach for high-risk disease.

In conclusion, quadruplet combinations have become the most effective therapy we can offer in the NDMM setting, making them the new standard of care. We're moving toward dual-maintenance therapy with Darzalex and Revlimid [D-R], which provides the best sustained MRD. We might begin using MRD-guided approaches in the very near future. 

Early relapse

Although new approaches to the treatment of NDMM are producing excellent results for many patients, giving them their longest remissions, myeloma is a disease that typically relapses.
Studies of patients who have had 1 to 3 prior lines of therapy included the drug belantamab mafodotin, which was previously approved by the U.S. Federal Drug Administration (FDA), then removed from the market. There are 2 important studies with belantamab, DREAMM-7 and DREAMM-8. Patients in one of the studies had 3 years of remission on average!

DREAMM-7 (https://www.myeloma.org/videos/dreamm-7-bvd-vs-dvd-relapsed-refractory-multiple-myeloma-phase-3-survival-efficacy-update) combined belantamab, Velcade, and dexamethasone [BVd], demonstrating PFS and a trend to an overall survival (OS) advantage. DREAMM-8 (https://www.myeloma.org/videos/dreamm-8-study-belantamab-mafodotin-plus-pomalidomide-dexamethasone-shows-improved-outcomes) combined belantamab, Pomalyst® (pomalidomide), and dexamethasone [BPd], demonstrating a significantly longer median PFS (mPFS). We hope to have belantamab back in the clinic very soon as it is an easily delivered and highly effective treatment. 

There was an interesting study of delivering Sarclisa. Historically, it has been given as an intravenous (IV) infusion. The new form of subcutaneous (in-the-skin) delivery is a device called on-body injector (OBI). It sticks to the skin, and a tiny needle pushes Sarclisa into the skin over about 12-13 minutes. Isa OBI had a similar safety profile to Isa IV, and patients appreciated the OBI method, which might mean that patients could receive it at home in the future. 

A series of studies focused on the early relapse setting for bispecific antibodies, “off-the-shelf” drugs that are currently used in late relapse. Having more options for patients in early relapse to be treated with these highly effective therapies is a very positive sign. 

Late relapse

Treatments for patients who have had at least 4 prior lines of therapy are the focus of a number of amazing clinical trials. Below is an overview of just a few areas of study.

CAR T-cell therapy 

• Standard of care CAR T-cell therapy (https://www.myeloma.org/emerging-therapies/car-t-cell-therapy)is emerging as the most effective treatment of relapsed myeloma, even in heavily pretreated patients. Arguably the most impactful and exciting of all the abstracts presented at ASCO and EHA meetings was the long-term follow-up of the CARTITUDE-1 clinical trial. (https://www.myeloma.org/videos/cartitude-1-final-results-ciltacabtagene-autoleucel-heavily-pretreated-relapsedrefractory) Study patients received Carvykti® (cilta-cel) as a one-time CAR T-cell infusion. Remarkably, 33% of patients who received Carvykti are still completely disease-free 5 years later. I'm not saying that these patients are cured, but this unprecedented outcome does raise the question of how do we define cure in myeloma? 
• Novel CAR T-cell therapy is another exciting area of research in late relapse is the development of new CAR T-cell therapies. In particular, a drug called anitocabtagene autoleucel (anito-cel) has a different design than the previous CAR T-cell therapies, and seems to have a just as high a rate of response as previous CAR T-cell therapies but with fewer neurological side effects. 
   

Combination bispecific antibodies

Bispecific antibodies (https://www.myeloma.org/emerging-therapies/bispecific-therapies) have two arms; one arm of the drug binds to the myeloma cell while the other arm binds to a T cell. The RedirecTT-1 clinical tria (https://www.myeloma.org/videos/redirectt-1-study-dual-targeting-bcma-gprc5d-rrmm-patients-teclistamab-talquetamab)l studied the combination of two bispecific therapies, Tecvayli®(teclistamab) and Talvey® (talquetamab), giving them together to patients whose myeloma has historically been very difficult to treat and control. Patients with extramedullary disease (EMD) have myeloma outside of the bone. Remarkably, when the RedirecTT-1 study combined these two bispecific therapies to treat EMD, the response rate was more than 80%, something we've not seen before in myeloma. This approach could give us a great option to treat EMD. 

Please note that a new bispecific antibody was approved by the FDA in July 2025 (https://www.myeloma.org/news-events/multiple-myeloma-news/fda-approval-lynozfic-linvoseltamab-rrmm). You can read more about Lynozyfic™ (linvoseltamab-gcpt) immunotherapy here (https://www.myeloma.org/treatment/multiple-myeloma-medications/lynozyfic-linvoseltamab-gcpt).

Trispecific antibodies

Trispecific antibodies have two arms that bind to the myeloma cell while the third arm binds to a T cell. This allows the drug to be even more precise than bispecific antibodies. Studies of trispecifics have demonstrated strong response rates, with less side effects than with bispecifics. This might mean that we will be able to deliver more effective and safer therapies in the near future. 

• The BCMA-GPRC5D trispecific antobody has demonstrated strong efficacy and significantly less toxicity than a combination of drugs. It has the potential to supplant sequential use of bispecific antibodies. 
• The BCMA-CD38 trispecific antibody also has impressive efficacy and tolerability and may confer another option for late relapse of myeloma. 
   

High-risk Multiple Myeloma (HRMM) Definition

High-risk multiple myeloma (HRMM) remains challenging to treat. It requires an intense approach with sustained MRD as the goal. To conduct clinical trials that are focused on patients with HRMM, a consensus definition is essential. A consensus on the definition of HRMM is a critical step toward risk-stratified therapeutic approaches.

Members of the IMWG and the International Myeloma Society (IMS) have now reached consensus on how to define HRMM and recommend the use of this definition in all clinical trials going forward, as well as in clinical practice. Based on the new definition, the HRMM subset of patients represent around 20% of NDMM patients. 

The Continuous Pursuit of a Myeloma Cure

All of the above-noted developments will lead to new and more effective treatment options for patients with myeloma. The IMF continues to drive forward our mission of improving the quality of life of myeloma patients while working toward prevention and a cure. Our vision is a world where every myeloma patient can live life to the fullest, unburdened by the disease.
 

If you liked this week's blog, more articles like this one will be available n the upcoming issue of our quarterly journal Myeloma Today. Sign up at subscribe.myeloma.org (https://my.myeloma.org/l/1077653/2024-10-09/bjz7xr) for Myeloma Today and for our weekly e-newsletter Myeloma Minute.

Also, you can contact the IMF InfoLine with your myeloma-related questions and concerns. Phone lines are open 9 a.m. to 4 p.m. (Pacific) Monday through Thursday and 9 a.m. to 2 p.m. on Friday at 1.800.452.CURE in the U.S. and Canada and 1.818.487.7455 worldwide. To submit your query electronically, email [email protected] (mailto:[email protected]). You can also schedule a call with an InfoLine Coordinator (https://www.myeloma.org/infoline).