CAR-T Cell Therapy in Multiple Myeloma

Introduction to CAR-T Cell Therapy

The FDA has approved CAR-T cell therapy, specifically idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), for adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including lenalidomide, pomalidomide, and daratumumab, based on superior efficacy even in heavily pretreated populations 1, 2, 3

The FDA has approved ide-cel for adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody 1, 2
The KarMMa Phase 2 trial demonstrated a 73% overall response rate with a 33% complete response rate in 128 patients with a median of 6 prior lines of therapy, where 94% were refractory to anti-CD38 antibody 1, 2, 3
The CARTITUDE-1 trial evaluated 97 patients with a median of 6 prior lines, with 88% being triple-class refractory, and demonstrated a 96.9% overall response rate with 34% MRD-negative complete response or stringent complete response 1, 3, 4

Both ide-cel and cilta-cel are BCMA-targeting CAR T-cell constructs administered after lymphodepleting chemotherapy 1, 2, 3
BCMA promotes MM pathogenesis in the bone marrow microenvironment and is a specific MM target antigen 1, 2, 4

Patients with triple-class refractory disease are ideal candidates for CAR-T therapy 1, 3
CAR-T therapy is the preferred option after failure of triple-class therapy rather than continuing with additional chemotherapy combinations 1, 2, 3

For patients who have exhausted lenalidomide, pomalidomide, and daratumumab, ide-cel or cilta-cel should be prioritized over belantamab mafodotin 1, 2, 4
CAR-T therapy demonstrates markedly superior efficacy with 71-97% response rates compared to belantamab mafodotin 1, 2, 4, 7

Continued expression of BCMA in some patients relapsing on BCMA-based therapies provides the option of continuing to target this antigen 1, 2, 3, 4
Bispecific antibodies, such as teclistamab, showed promising outcomes post-CAR-T failure with a 62% overall response rate and 9-month PFS of 58.5% in triple-class exposed patients 3, 4