Progress and Promise: Advancing Treatment in Relapsed/Refractory Multiple Myeloma

Session Overview and Highlights

R/R MM: Focus on CAR T

The faculty emphasized that most of their patients are candidates for CAR T, which has fewer age and frailty restrictions than autologous transplants. Ineligibility for CAR T often stems from logistical or social factors, like lack of caregiver support or proximity to treatment centers. The selection between the 2 BCMA-directed CAR T products—ide-cel and cilta-cel—depends on factors such as efficacy, toxicity, and the patient’s age or frailty. Cilta-cel is preferred for its superior efficacy, whereas ide-cel is often chosen for older patients due to its more favorable toxicity profile, especially for those at a greater risk for neurotoxicity.

As CAR T is being used earlier in R/R MM, careful patient selection is crucial, particularly for high-risk patients. Despite the broader indication, early referrals from community oncologists remain relatively rare. The faculty noted positive data from the CARTITUDE-4 trial (NCT04181827), which demonstrated improved progression-free survival and overall survival for high-risk cytogenetic and extramedullary disease (EMD) populations with cilta-cel, although they hoped for stronger efficacy results in the EMD group. The key takeaway for community oncologists is the importance of early referral for CAR T evaluation.

Emerging CAR T and ADC Therapies in R/R MM

The faculty discussed the potential role of anito-cel in comparison with existing BCMA-directed CAR T therapies, noting that its advantage over cilta-cel is its absence of delayed neurotoxicity in preliminary data. However, the faculty note that longer-term data with anito-cel are needed to confirm these results. The faculty also expressed enthusiasm for emerging CAR T therapies with targets (other than BCMA), but more data is needed to determine their place in therapy for R/R MM.

The faculty anticipate that belantamab mafodotin, a BCMA-directed ADC, will be reapproved and could have a potential role in patients who are ineligible for CAR T. They highlight the importance of physicians still referring patients to CAR T early, even with belantamab pending availability.

Late R/R MM: Focus on Bispecific Antibodies

The faculty discussed integrating bispecific antibodies into the current treatment landscape, with priority given to CAR T when possible. In the post-BCMA CAR T setting, GPRC5D-directed talquetamab is seen as particularly beneficial, although GPRC5D-related toxicities limit long-term use. There is increased interest in potential “re-treatment” of a BCMA-directed bispecific post-BCMA CAR T; however, the remission-free period of optimal timing is to be determined. Real-world data showed that bispecific antibodies delivered efficacy comparable to reference trials.

The faculty also supported using prophylactic tocilizumab to reduce CRS and improve outpatient transitions for treatment initiation, although reimbursement concerns remain. They suggested maximizing more cost-effective approaches, such as prophylactic steroids, to enhance community adoption.

Emerging Bispecific Antibodies and Combination Strategies in R/R MM

The faculty were impressed with the LINKER-MM1(NCT03761108) data on linvoseltamab, noting its strong efficacy and safety, although concerns were raised about its adoption as the third BCMA-directed bispecific antibody to market. They also discussed the promising efficacy of talquetamab and teclistamab combination therapy from the RedirecTT-1 (NCT04586426) study, particularly in patients with EMD, but acknowledged this regimen requires diligent monitoring for toxicities. The group expressed eagerness for efficacy data on emerging therapies like trispecific antibodies.

Discussion Themes and Expert Insights

The treatment landscape of R/R MM is rapidly evolving, emphasizing the importance of early referral for CAR T, particularly at first or second relapse. The faculty members stressed the importance of community oncologist education and engagement to help navigate the expanding range of treatment options. There was consensus on emerging CAR T products and trispecific antibodies making a significant impact in the future, with bispecifics potentially moving to earlier lines of treatment. The combination of talquetamab and teclistamab was highlighted as especially promising for EMD, offering hope for high-risk populations. The key message was that all MM patients should receive at least one T-cell redirecting therapy in their treatment journey, with the overall progress in the field signaling a future where myeloma could potentially be cured.

Unmet Needs and Recommendations

Although the long-term data of cilta-cel have prompted unprecedented discussion on potentially curative intent for MM, the key focus should be given to reducing delayed neurotoxicity to increase CAR T use at early relapse. Another area of focus of future studies includes determining the underlying biology of patients who do not respond to bispecific antibodies. Long-term efficacy data and durability of response of emerging therapies are needed to determine their role in the treatment landscape of R/R MM.

Conclusion

The discussion underscores the rapidly evolving R/R MM landscape and the importance of continued research to improve survival outcomes while minimizing toxicity. Despite the approval of CAR T therapy in the earlier lines, referrals from the community oncologists in early relapse remain relatively limited. Emerging novel CAR T products, bispecific antibodies, and pending reapproval of ADC therapy offer exciting additions to the current treatment landscape. However, optimizing sequencing strategies to individualize treatment selection will become increasingly challenging.

References

NCCN. Clinical Practice Guidelines in Oncology. Multiple Myeloma, version 1.2026. Accessed June 24, 2025. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf

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