Clinical Perspectives in Current and Emerging CAR T Therapies for Early R/R MM
Panelists discuss how current chimeric antigen receptor (CAR) T therapies for early relapsed/refractory multiple myeloma (R/R MM) include both ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), both targeting the B-cell maturation antigen (BCMA), with cilta-cel showing superior outcomes in second-line patients compared with ide-cel’s performance in third- and fourth-line settings. They also emphasize that regardless of which CAR T is used, both significantly outperform standard-of-care treatments. Looking toward the future, emerging CAR T therapies are targeting new antigens like GPRC5D on myeloma cells, with phase 2 clinical trials already enrolling patients whose disease returned after initial CAR T treatment, offering hope for sequential CAR T approaches as the field moves toward increasingly immunotherapy-focused treatment strategies.
Two FDA-approved CAR T therapies are currently available in the United States for MM treatment, both targeting BCMA, which has proven to be a highly effective target for myeloma cells. Cilta-cel was the therapy used in the CARTITUDE-4 trial that demonstrated spectacular outcomes, setting a benchmark for treatment efficacy. Ide-cel was the initially approved CAR T therapy and has its own clinical trial, KarMMa-3, though it targets patients at second line and beyond rather than cilta-cel’s earlier intervention approach.
The clinical trial designs differ between these therapies, with cilta-cel evaluated in first-line relapsed patients, whereas ide-cel was studied in second-line and beyond populations, making direct comparisons challenging. Despite targeting later-line patients who typically have more treatment-resistant disease, ide-cel still achieved approximately 70% response rates and 30% to 40% complete remission rates, though somewhat lower than cilta-cel’s results. Regardless of these differences, both CAR T therapies consistently outperform standard-of-care treatments when compared head-to-head, establishing CAR T as a groundbreaking therapeutic approach that should be prioritized for eligible patients.
The future of MM treatment will be heavily focused on immunotherapy approaches, with researchers actively developing next-generation CAR T therapies targeting different antigens on myeloma cells. The next target being explored is GPRC5D, already in clinical trials as a CAR T therapy for patients whose disease progresses after initial CAR T treatment. The University of Kansas has an active phase 2 clinical trial enrolling patients whose myeloma returns after cilta-cel, offering them a different CAR T therapy with this alternative target. Early data presented at medical conferences and clinical experience suggest this approach is effective, with all enrolled patients showing positive responses, indicating a bright future for sequential CAR T treatments in MM management.
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