Source: Myeloma – Hematology Advisor
The Food and Drug Administration (FDA) has approved Abecma® (idecabtagene vicleucel; ide-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody (triple-class-refractory). This approval allows patients with relapsed/refractory multiple myeloma to receive the T-cell therapy earlier than previously indicated.
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 expanded approval was based on data from the KarMMa-3 study (ClinicalTrials.gov Identifier: NCT03651128), which evaluated Abecma in patients with relapsed or refractory multiple myeloma who had received 2 to 4 lines of prior therapy. Study participants were randomly assigned to receive Abecma (n=254) or standard regimens (n=132). The primary endpoint was progression free survival (PFS); other measures included overall response rate and overall survival.
Results showed treatment with Abecma led to statistically significant improvement in PFS compared with standard regimens (hazard ratio, 0.49 [95% CI, 0.38-0.64]; P <.0001). Median PFS was 13.3 months (95% CI, 11.8-16.1) in the Abecma arm and 4.4 months (95% CI, 3.4-5.9) in the standard regimens arm.
Overall response rate was 71% (95% CI, 66-77) with Abecma and 42% (95% CI, 33-50) with standard regimens (P <.0001). Median duration of response (DOR) was 14.8 months (95% CI, 12.0-18.6) in the Abecma group and 9.7 months (95% CI, 5.4-16.3) in the standard regimens group. In those patients with complete response or better, the median DOR was 20 months (95% CI, 15.8-24.3). At the time of data cutoff, overall survival data were immature.
“Abecma has demonstrated a progression free survival benefit 3 times that of standard regimens in relapsed or refractory multiple myeloma, and we are now bringing the promise of cell therapy to patients earlier in their treatment journey,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb.
As for safety, cytokine release syndrome occurred in 88% of patients who received Abecma; 5% of events were grade 3 or higher. Neurotoxic effects occurred in 15% of the Abecma-treated patients; 3% were grade 3 or higher.
The prescribing information for Abecma includes a Boxed Warning regarding the risk of cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, 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 administered as a single dose for infusion containing a suspension of CAR- positive T cells in 1 or more infusion bags. The new recommended dose range is 300 to 510 x 106 CAR-positive T cells.