Initial results from CAR-T cell therapy in MM: KarMMa

In patients with relapsed and refractory multiple myeloma, data from patients treated with idecabtagene vicleucel (ide-cel) support a favourable benefit-risk profile for ide-cel across the target dose levels of 150 to 450 × 10⁶ CAR-T cells.

Prof. Jesús San Miguel (University of Navarra, Spain) presented the updated results from the pivotal, phase 2 evaluating the efficacy and safety of investigational B-cell maturation antigen (BCMA)-directed chimaeric antigen receptor (CAR) T cell immunotherapy, ide-cel, in patients with relapsed and refractory multiple myeloma [1].

In the study, 128 patients with heavily pre-treated relapsed and refractory multiple myeloma who were exposed to at least three prior therapies and were refractory to their last regimen per the International Myeloma Working Group (IMWG) definition (no response to therapy or disease progressed within 60 days) were treated with ide-cel across target dose levels of 150-450 x 10⁶ CAR T cells. Patients had a median of 6 prior regimens; 84% were refractory to all 3 classes of commonly used treatments including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and 94% were refractory to anti-CD38 antibodies. At data cut-off (January 2020), the median duration of follow-up was 13.3 months.

The overall response rate (ORR) was 73% across all dose levels, including 33% of patients who had a complete response (CR) or stringent CR (sCR) (Table), in a seemingly dose-dependent manner. Median duration of response (DoR) was 10.7 months, with 19.0 month median DoR for patients who had a CR or sCR. Median progression-free survival (PFS) was 8.8 months, with 20.2 month median PFS for patients who had a CR or sCR. All patients who had CR or sCR and were evaluable for minimal residual disease (MRD), were MRD-negative. Clinically meaningful benefit was consistently observed across subgroups, and nearly all subgroups had an ORR of 50% or greater, including older and high-risk patients. The overall survival (OS) data continue to mature, with an estimated median OS of 19.4 months across all dose levels and 78% of patients alive at 12 months.

Table 1. Patient outcomes of the KarMMa study with a median follow-up of 13.3 months

1. San Miguel J, et al. Idecabtagene vicleucel (IDE-CEL; BB2121), a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: initial KARMMA results. EHA25 Virtual, 11-21 June 2020, Abstract S209.

Posted on 9 September, 202023 February, 2021