FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma

Abstract

In March 2021, the FDA approved idecabtagene vicleucel, a chimeric antigen receptor T-cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DOR) in 100 adult patients with RRMM treated with idecabtagene vicleucel in a single-arm trial. Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Of the 100 patients in the efficacy evaluable population, ORR was 72% [95% confidence interval (CI), 62–81] with stringent CR rate of 28% (95% CI, 19–38). After median follow-up of 10.7 months, median DOR was 11 months (95% CI, 10.3–11.4) in responders (partial response or better) and 19 months [95% CI, 11.4 months, not estimable (NE)] in patients who achieved stringent CR. Serious adverse reactions occurred in 67% of 127 patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively, leading to a Risk Evaluation and Mitigation Strategy. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4%, with two fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% (3/127), with two fatalities.

Genetic Modification of T Cells for the Immunotherapy of Cancer

“…We also found that a lower number of CAR transduced T cells are needed (generally less than 1 × 10 8 transduced T cells) to achieve objective clinical responses than TCR transduced T cells (unpublished). These promising results have led to FDA approval of five CAR T cell products: an anti-CD19 CAR with a 4-1BB costimulatory cassette called tisagenlecleucel (Kymirah-Novartis) , an anti-CD19 CAR with a CD28 costimulatory cassette called axicabtagene (Yescarta-Kite/Gilead), an anti-BCMA CAR with a 4-1BB costimulatory cassette called idecabtagene (ABECMA-Celgene/BMS), an anti-CD19 CAR with a 4-1BB costimulatory cassette called lisocabtagene (Breyanzi-Juno/BMS), and an anti-CD19 CAR with a CD28 costimulatory cassette called brexucabtagene (Tecartes-Kite/Gilead) [ 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 ]. The encouraging results obtained with CAR T cells targeting B cell malignancies have not been recapitulated in studies targeting solid tumors [ 144 ].…”

CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

“…In addition to the aforementioned Tecartus approval for r/r adult B-ALL, the additional registrations included axicabtagene ciloleucel (Yescarta) for r/r adult FL [ 18 ], and lisocabtagene maraleucel (Breyanzi) for adult r/r DLBCL, r/r PMBCL, grade 3B FL [ 21 ]. Moreover, in 2021, we witnessed the first approval of a BCMA-directed CAR-T therapy designated for adult r/r MM patients who had failed at least four previous lines of treatment [ 24 ]. Indeed, the efficacy of idecabtagene vicleucel (Abecma) was evaluated in the pivotal KarMMa clinical trial [ 23 ].…”

“…Indeed, the efficacy of idecabtagene vicleucel (Abecma) was evaluated in the pivotal KarMMa clinical trial [ 23 ]. Stringent CR (sCR) was detected in only 28%, however, the CAR-T cells were administered to patients with a significant number of prior lines of treatment (median of 6 lines) [ 24 ]. Importantly, 65% of the patients who achieved sCR had a durable response for at least 12 months.…”

Emerging Role of Antibody-Drug Conjugates and Bispecific Antibodies for the Treatment of Multiple Myeloma

“…In response to this incremental increase in dose, a CR was observed in 50%, 69%, and 81% of patients, respectively. As of March 2022, the KarMMa trial provided significant evidence to support FDA approval of ide-cel for RRMM [ 111 ].…”