This year brought major advances across the multiple myeloma continuum, with new data on CAR T-cell sequencing and delivery and the emergence of additional cellular and bispecific therapies that offer meaningful gains for patients, particularly in the relapsed or refractory setting.
Real-world evidence presented during a Case-Based Roundtable led by Dr. Jorge Monge showed that patients who were naive to B-cell maturation antigen (BCMA)-targeted therapies achieved higher response rates and longer progression-free survival than those previously exposed. Reported overall response rates were 92% versus 70% for BCMA-naive versus BCMA-exposed patients. A direct comparison of approved CAR T products indicated that ciltacabtagene autoleucel (cilta-cel; Carvykti) produced higher complete response rates (70% vs 47%) and improved survival outcomes compared with idecabtagene vicleucel (ide-cel; Abecma), though cilta-cel was associated with increased toxicity.
Experts at a separate Case-Based Roundtable, including Dr. Konstantinos Sdrimas and community oncologists, emphasized that seamless coordination between community and academic centers is essential for successful CAR T therapy. Key priorities include selecting bridging therapies that preserve future treatment options, anticipating and managing immune effector cell-associated neurotoxicity syndrome (ICANS), and ensuring early recognition of toxicities. Most patients return to community care within about 30 days after infusion, and long-term management depends on shared protocols for vaccinations, intravenous immunoglobulin replacement, and monitoring for late-onset adverse effects.
At the 2025 EHA Congress, phase 2 iMMagine-1 data showed that anitocabtagene autoleucel (anito-cel) produced a 97% overall response rate in heavily pretreated relapsed/refractory myeloma after roughly one year of follow-up. Sixty-eight percent of patients achieved a stringent complete response and 93% reached minimal residual disease negativity. Anito-cel uses a D-Domain binder intended to enhance cell stability and transduction efficiency. Safety was manageable, with mostly low-grade cytokine release syndrome and a 1% rate of grade 3 ICANS. Anito-cel is advancing into the phase 3 iMMagine-3 trial for earlier lines of therapy.
Pooled results from the phase 1 MajesTEC-2 and TRIMM-2 trials, discussed by Dr. Anita D’Souza, found the triplet of teclistamab (Tecvayli), daratumumab (Darzalex), and pomalidomide (Pomalyst) to be a feasible option for relapsed/refractory disease. The analysis reported an 88.5% overall response rate, with 61.5% achieving complete response or better and a median progression-free survival of 26.5 months. Neutropenia and infections were common; immunoglobulin replacement reduced serious infectious complications. While cohort sizes were small and additional studies are ongoing, the combination appears to be a viable, immunologically grounded option with careful infection monitoring.
Results from the phase 1/2 MonumenTAL-1 trial showed that talquetamab (Talvey), a GPRC5D-directed bispecific antibody, produced robust responses in heavily pretreated, high-risk patients. Overall response rates ranged from about 70% to 74% across dosing schedules, and patients previously treated with T-cell redirection therapies had an ORR of 66.7%. Patients with high-risk cytogenetics and those with penta-refractory disease also experienced substantial benefit, with median durations of response reaching 18 months in some cohorts. Talquetamab’s deep and durable activity in difficult-to-treat populations supports its role as an important later-line treatment option.
Collectively, these developments broaden therapeutic options and underscore the importance of treatment sequencing, coordinated care, and vigilant toxicity management in modern myeloma practice.
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