The Food and Drug Administration (FDA) has approved Abecma (idecabtagene vicleucel) for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. It is a customized treatment using the patient’s own T cells that have been genetically modified to include a new gene to target and destroy myeloma cells. Antigen-specific activation of Abecma results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.
The approval was based on data from the open-label, single-arm, multicenter phase 2 KarMMa study (ClinicalTrials.gov: NCT03361748) that evaluated the efficacy and safety of Abecma in 127 adults with relapsed or refractory multiple myeloma who received at least 3 prior lines of therapy. The primary endpoint was the overall response rate (ORR). A key secondary endpoint included the duration of response (DOR).
Among the efficacy evaluable population (n=100), the ORR was 72% (95% CI, 62-81), of which 28% of patients (95% CI, 19-38) achieved a stringent complete response (sCR), 25% (95% CI, 17-35) achieved very good partial response (VGPR), and 19% (95% CI, 12-28) achieved partial response (PR). The median time to response was 30 days (range, 15-88 days) and the median DOR was 11 months (95% CI, 10.3-11.4) for all responders.
Additionally, the median DOR was 19 months (95% CI, 11.4-not estimable) for sCR patients and 11.1 months (95% CI, 8.7-11.3) for VGPR patients. Of the 28 patients who achieved sCR, an estimated 65% (95% CI, 42-81) had remission lasting at least 12 months.
As for safety, the most common nonlaboratory adverse reactions with Abecma were cytokine release syndrome, infections (pathogen unspecified), fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite. The most common laboratory adverse reactions included neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
Abecma carries a Boxed Warning regarding the risk of cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and prolonged cytopenia, all of which can be fatal or life-threatening. It is available only through a restricted program called the Abecma REMS.
Abecma is supplied in 50mL, 250mL, and 500mL infusion bags containing a frozen suspension of genetically modified autologous T cells in 5% DMSO. A single dose of Abecma contains a cell suspension of 300 to 460 x 106 CAR-positive T cells in 1 or more infusion bags.
1. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the first anti-BCMA CAR T Cell therapy for relapsed or refractory multiple myeloma. [press release]. Princeton, NJ and Cambridge, MA: Bristol Myers Squibb and bluebird bio, Inc.; March 26, 2021.
2. FDA approves first cell-based gene therapy for adult patients with multiple myeloma. [press release]. Silver Springs, MD: US Food and Drug Administration; March 27, 2021.
3. Abecma [package insert]. Summit, NJ: Bristol Myers Squibb; 2021.