This year brought major advances across the multiple myeloma continuum, underscoring a rapidly evolving treatment landscape. New data on CAR T-cell sequencing and delivery, alongside progress with cellular and bispecific therapies, offered meaningful clinical gains for patients, particularly in the relapsed or refractory setting.
Real-world evidence presented at a Case-Based Roundtable and discussed by Dr Jorge Monge indicated that patients naive to B-cell maturation antigen–targeted therapies achieved higher response rates (92% vs 70%) and longer progression-free survival after CAR T-cell therapy than those previously exposed. A comparative analysis also showed that ciltacabtagene autoleucel (cilta-cel; Carvykti) produced higher response rates and better survival outcomes than idecabtagene vicleucel (ide-cel; Abecma), though cilta-cel was associated with increased toxicity.
Speakers at a separate Case-Based Roundtable, including Dr Konstantinos Sdrimas and community oncologists, emphasized that coordination between community and academic centers is essential for successful CAR T-cell therapy. Key points included careful selection of bridging therapies to avoid treatments that could compromise later options, early recognition and management of neurotoxicities such as immune effector cell–associated neurotoxicity syndrome (ICANS), and the typical transition of patients back to community care within 30 days post-infusion. Long-term management depends on shared protocols for vaccinations, intravenous immunoglobulin use, and monitoring for late-onset adverse effects.
At the 2025 EHA Congress, phase 2 iMMagine-1 trial results showed that anitocabtagene autoleucel (anito-cel) produced a 97% overall response rate in heavily pretreated relapsed/refractory multiple myeloma after about one year of follow-up. Sixty-eight percent of patients achieved a stringent complete response and 93% reached minimal residual disease negativity. The therapy uses a D-Domain binder to improve cell stability and transduction efficiency. Safety was manageable, with predominantly low-grade cytokine release syndrome and a 1% rate of grade 3 ICANS. Anito-cel has advanced to the phase 3 iMMagine-3 trial for earlier lines of treatment.
Pooled data from the phase 1 MajesTEC-2 and TRIMM-2 trials, discussed by Dr Anita D’Souza, found that the triplet regimen of teclistamab (Tecvayli), daratumumab (Darzalex), and pomalidomide (Pomalyst) is feasible for relapsed/refractory multiple myeloma. The analysis reported an 88.5% overall response rate, a 61.5% rate of complete response or better, and a median progression-free survival of 26.5 months. Neutropenia and infections were common, but immunoglobulin replacement helped reduce severe infectious complications. Investigators noted the small cohort size and ongoing studies of alternative regimens, while highlighting the triplet as a viable option when infection monitoring is maintained.
Results from the phase 1/2 MonumenTAL-1 trial showed that talquetamab (Talvey), a GPRC5D-directed bispecific antibody, produced strong efficacy in heavily pretreated, high-risk relapsed/refractory multiple myeloma. Overall response rates ranged from about 70% to 74% across dosing schedules, with a 66.7% response rate among patients previously exposed to T-cell redirection therapies. Patients with high-risk cytogenetics and penta-refractory disease achieved durable responses, with median duration of response reaching 18 months in some cohorts. Experts say talquetamab’s ability to deliver deep, durable responses in difficult-to-treat populations positions it as a key later-line therapy.
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