Myeloma Experts Summarize Key Themes From the 22nd Annual IMS Meeting and Exposition

The 22nd Annual International Myeloma Society (IMS) Meeting and Exposition presented a comprehensive review of the current standards of care (SOCs) for patients with multiple myeloma across disease settings, as well as developments that may challenge these standards as further research emerges. During the meeting, OncLive® collected expert commentary about some of the biggest developments in myeloma management.

What Data Show the Efficacy of Moving Anti-BCMA Therapies to the First-Line Myeloma Setting?

“There have been so many great developments at this meeting,” Andrew Yee, MD, of Massachusetts General Hospital in Boston, said. “[One] key theme that has emerged is: How do we [advance] the therapies that have been used for relapsed patients, in particular the anti-BCMA therapies? These therapies work amazing after multiple lines of prior therapy. How do we move them forward to earlier lines of therapy and to newly diagnosed [patients]?

“We saw data presented looking at [these agents in] transplant-eligible and transplant-ineligible newly diagnosed patients. Some of the initial data look amazing in terms of depth of response. We are moving the ball forward closer toward a cure with these therapies.”

“It’s difficult to get practice-changing data at every congress,” Paula Rodriguez-Otero, MD, PhD, of the Clinica Universidad de Navarra Pamplona in Spain, contextualized. “But at this congress, we got a lot of data from combinations with bispecific antibodies. For example, we have cevostamab (RG6160, BFCR4350A) in combination with pomalidomide [(Pomalyst) and dexamethasone in patients with BCMA-directed therapy–naive relapsed/refractory multiple myeloma, and the phase 2] MajesTEC-5 [(NCT05695508) trial data of teclistamab-cqyv (Tecvayli)–based induction therapy in patients with newly diagnosed disease were] presented. Elranatamab-bcmm [(Elrexfio) data] in newly diagnosed [patients were also presented]; [there were] a lot of data with bispecific antibodies in earlier lines. These studies are not practice changing today because they are all preliminary but will eventually change the way we manage myeloma in the future.”

Further reading: During the meeting, OncLive also reported findings from the phase 1 DREAMM-9 trial (NCT04091126) and the phase 1/2 BelaRd trial (NCT04808037), which both investigated combinations with the BCMA-directed antibody-drug conjugate belantamab mafodotin-blmf (Blenrep) in patients with newly diagnosed disease.1,2

What Are the Optimal Myeloma Patient Populations for Bispecific Antibodies and CAR T-Cell Therapies?

“I appreciated the data about the importance of better stratifying patients, better understanding who is at high risk,” Claudio Cerchierone, MD, PhD, of the Università di Bologna in Italy, explained. “We have seen in the frontline setting that quadruplets should absolutely be the SOC starting not tomorrow but today. We have seen idea of the integration of isatuximab-irfc [Sarclisa] as a new [therapy] in both transplant-eligible and -ineligible [patients].

“In terms of relapsed/refractory [disease], interesting data are anticipating bispecific antibodies in earlier relapsed [settings], and elranatamab in combinations will be interesting; I look forward to seeing more solid long-term data. New [data] about CAR T-cell therapy [were presented] from the early relapsed [setting are emerging], and we should better understand how to use [these therapies] and what is the best moment to integrate them. Additionally, evaluations about bridging therapies to CAR T-cell therapies and other cellular therapies are interesting.

“In general, we also need drugs that are active not only on BCMA, which we have a lot of bispecific antibodies and CAR T-cell therapies for, but also other agents. We are going to explore other new potential targets that we need because some patients are unfortunately refractory [to treatment]. There are also some data with translational research that aim to develop target-driven approaches. We should not forget other settings. Extramedullary disease continues to remain an important problem, and I saw interesting data with novel agents focusing on this setting.

“I also presented an important study about the latency of the action of bispecific antibodies. These drugs function not only in the immediate moment of administration, but also in the long term. This study fully evaluated this point. Maybe [we can] delay the dose in patients responding well according to these data. The future will be to [conduct] studies not only about the many combinations but also about translational research. This is the key point, to understand who the best responders are and how we can compare [their characteristics with those of] with the poor responders to understand how to improve and optimize the use of the brilliant drugs we are going to have in our daily practice.”

“[It was] interesting to see a lot more data presented on the translational aspects,” Yi Lin, MD, PhD, of Mayo Clinic in Rochester, Minnesota, stated. “[Investigators are] looking at all these different tools we have for multiomic studies that can be done to understand the biologies of why some patients get severe toxicities or [whether] there are immune profiles vs myeloma risk features for responders to these immunotherapies. None of these are necessarily ready for a clinical assay this year, however, this is important foundational information to build upon so we can be smarter about how we select patients and how we design the next-generation trials.”

“There were a lot of abstracts talking about how to improve CAR T-cell therapy or bispecific antibody therapy, and abstracts that will help us understand what factors—either genetic factors or microenvironmental factors—contribute to relapse,” Oliver Van Oekelen, MD, PhD, of Icahn Mount Sinai in New York, New York, added. “Understanding that will make a big difference and will help us improve the therapies that are currently available as we develop new ones in clinical trials.”

“I was interested in the evaluation of patients who had stopped bispecific antibody therapy for various reasons and experienced long-term remission despite having stopped therapy,” Marc S. Raab, MD, PhD, of University Hospital Heidelberg in Germany, said. “That’s something we all experience in our patients from time to time, and everyone is discussing that. Could that be a way forward to stop, at some point, the long-term bispecific antibody therapy?

“The data suggested, for example, that it is feasible. However, the recovery rate of the immune system seemed to have taken longer than expected until the endogenous IgG production kicked in. That needs to be prospectively tested; this was a retrospective study but addressed an important point and interesting question [that arises] in daily routine practice.”

Further reading: OncLive reported on CAR T-cell therapy highlights from the meeting, including data with arlocabtagene autoleucel (BMS-986393) and equecabtagene autoleucel in relapsed/refractory disease.3,4

What Are the Potential Future Implications of Research With Subcutaneous Isatuximab-Based Regimens in Myeloma?

“Quadruplet regimens are the new SOC, amongst which is isatuximab [plus] bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone [Isa-VRd],” Xavier Leleu, MD, PhD, of Hôpital La Mileterie, hospital of Poitiers in France, said. “If we use those, the patients are, in regard to the myeloma, doing great. Should we stop there? No. There are still questions we need to answer.

“We fail patients who die from myeloma. We know the patients are likely to die from myeloma. We need to make treatments available worldwide. If you want to make your treatment available worldwide, if you want the patients to ultimately be happy and your teams to be able to treat more patients—because we see more patients with myeloma—you need to work on how to stop the treatment at some point. Remember, the patient is not cured. It’s a chronic disease.

“Can we stop the treatment without the myeloma resuming at some point, even in 10 years? The patient will not be technically cured because they will still have myeloma somewhere, but they will not develop myeloma anymore. This is a bit philosophical today, but this is the next step.

“[Regimens] like Isa-VRd and daratumumab plus VRd, [regardless of] how amazing they are, are probably not the best drugs for doing this. Isa-VRd is great because you stop bortezomib and dexamethasone and continue isatuximab and lenalidomide until progression. But maybe with the new generations of immunotherapy, CAR T-cell therapies, and the bispecific antibodies—particularly the BCMA-directed ones—we are going to deepen the [responses] even further from the quadruplet-based regimens, so we could try to stop [therapy]. Maybe the patient would relapse, but it would take years to relapse. Or, maybe [we would] not necessarily stop [treatment], but give an injection every 3 or 4 months, which means 3 or 4 injections a year. This would not be a problem for [many] patients. It would be pharmacokinetically acceptable. It would be safe, and the patients could handle that for years.

“The next step is: Can we extend or stop the treatment and not have the patient relapse? Is it possible with Isa-VRd? I don’t know. Is it possible with new immunotherapies, CAR T-cell therapies, bispecific antibodies? I’m not sure. We have to wait for the data, but I believe it’s the way to go.”

Further viewing: Watch Leleu describe quality-of-life outcomes with Isa-VRd in the phase 3 IRAKLIA study (NCT04644632).5

What Has Been the Evolution of Therapies for Multiple Myeloma Precursor Diseases?

“One of the most exciting sessions was the precursor disease session, on both a biological level and also an interventional level, trying to understand the biology of myeloma evolution and when the right time to intervene is, and for whom,” Elizabeth O’Donnell, MD, of Dana-Farber Cancer Institute in Boston, shared. “With the presentation of the [phase 3] AQUILA trial [NCT03301220] data at [the 2024 ASH Annual Meeting], and hopefully an FDA approval of daratumumab for high-risk smoldering myeloma, that whole setting is going to be transformed. We’re going to hear more topics both on the science level and on the therapeutic level over the next couple years.”

Further reading: During the conference, OncLive covered data with the use of linvoseltamab-gcpt (Lynozyfic) in patients with high-risk smoldering multiple myeloma.6

What Data Support the Potential Outpatient Administration of Therapies for Patients With Myeloma?

“More and more data support the outpatient [use of] bispecific antibodies and cell therapies, and [there are] more data regarding prophylactic tocilizumab [Actemra] and prophylactic steroids that can help lead to facilitation of outpatient bispecific antibodies and possibly even more community use of bispecific antibodies and cell therapies,” according to Larry Anderson, MD, PhD, of the University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center in Dallas.

“In the nursing symposium, there were abstracts and oral presentations on best practices to administer bispecific antibodies as outpatient [therapies],” Donna Catamero, ANP-BC, OCN, CCRC, of Mount Sinai, stated. “This is crucial for community settings, so community practices can rely less upon the academic centers. There are a lot of barriers for patients trying to get to academic centers to access these therapies. If we can properly administer these therapies in the outpatient setting, this leads to more opportunity to give these advanced therapies in the community, so patients don’t have to travel, [incur] loss of wages, [incur] loss of time, [or face barriers if they] don’t have the care partner support to travel long distances to academic centers. If we can figure out a way to properly administer these therapies in the outpatient setting, this will broaden the access of these therapies.”

Further viewing: In an interview with OncLive, Catamero reviewed challenges associated with administering myeloma therapies in the outpatient setting.7

References

1. Seymour, S. Stretched dosing schedule of belantamab mafodotin plus VRd is active, safe in transplant-ineligible myeloma. September 19, 2025. Accessed September 23, 2025. https://www.onclive.com/view/stretched-dosing-schedule-of-belantamab-mafodotin-plus-vrd-is-active-safe-in-transplant-ineligible-myeloma
2. Wahner A. Belantamab mafodotin triplet yields responses with low ocular toxicity in intermediate-fit or frail newly diagnosed myeloma. September 19, 2025. Accessed September 23, 2025. https://www.onclive.com/view/belantamab-mafodotin-triplet-yields-responses-with-low-ocular-toxicity-in-intermediate-fit-or-frail-newly-diagnosed-myeloma
3. Nadeem O. Dr Nadeem on efficacy and safety of arlo-cel for R/R myeloma. September 19, 2025. Accessed September 23, 2025. https://www.onclive.com/view/dr-nadeem-on-efficacy-and-safety-of-arlo-cel-for-r-r-myeloma
4. Fabbricatore R. Eque-cel demonstrates activity in R/R multiple myeloma. September 19, 2025. Accessed September 23, 2025. https://www.onclive.com/view/eque-cel-demonstrates-activity-in-r-r-multiple-myeloma
5. Leleu X. Dr Leleu on QOL outcomes with SC isatuximab via on-body delivery in R/R myeloma. September 20, 2025. Accessed September 23, 2025. https://www.onclive.com/view/dr-leleu-on-qol-outcomes-with-sc-isatuximab-via-on-body-delivery-in-r-r-myeloma
6. Wahner A. Linvoseltamab yields favorable safety profile and antimyeloma activity in high-risk smoldering myeloma. September 19, 2025. Accessed September 23, 2025. https://www.onclive.com/view/linvoseltamab-yields-favorable-safety-profile-and-antimyeloma-activity-in-high-risk-smoldering-myeloma
7. Catamero D. Catamero on challenges of community-based administration of bispecifics and CAR T-cell therapy in myeloma. September 18, 2025. Accessed September 23, 2025. https://www.onclive.com/view/catamero-on-challenges-of-community-based-administration-of-bispecifics-and-car-t-cell-therapy-in-myeloma