Bristol Myers Squibb and partner bluebird bio announced late Friday that the FDA approved their filing for the BCMA-directed personalised immune cell therapy Abecma (idecabtagene vicleucel) to treat patients with relapsed or refractory multiple myeloma. "CAR-T cell therapies have shown transformational potential for the treatment of haematologic malignancies," remarked Samit Hirawat, chief medical officer at Bristol Myers Squibb, adding "[we] are proud to bring the first CAR-T cell therapy to appropriate triple-class exposed patients…offering the chance for durable response."
The therapy is approved as a one-time infusion, with a recommended dose range of 300 to 460 x 106 CAR-positive T cells, for patients who have received at least four prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody. The decision also marks a first FDA approval for bluebird bio.
The companies said the FDA filing, assessed under priority review, was supported by data from the pivotal Phase II KarMMa trial of 127 patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy. The results, recently published in the NEJM, showed an overall response rate (ORR) of 72% among the 100 patients in the efficacy evaluable population.
Bristol Myers Squibb and bluebird bio indicated that patients saw effects of the treatment rapidly, with time to response ranging from 15 to 88 days, for a median of 30 days. Responses lasted a median 11 months for all responders, and increased to 19 months for the 28 patients who achieved a stringent complete response (sCR). The companies noted that among this latter cohort, an estimated 65% were in remission for at least a year.
Subgroup analyses of Abecma outcomes in high-risk and elderly patients were presented at the American Society of Hematology (ASH) conference last December. The companies said ORR and CR rates were ≥65% and ≥20%, respectively, for the majority of high-risk subgroups. Moreover, response rates for patients 65 years and over, as well as those 70-plus, were "comparable and consistent" with the overall treated KarMMa population. Median progression-free survival was 8.6 months in patients aged ≥65 years, and 10.2 months for those ≥70 years.
Abecma comes with a boxed warning regarding cytokine release syndrome (CRS), neurologic toxicities, haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and prolonged cytopaenia. According to Bristol Myers Squibb and bluebird bio, Abecma was associated with "mostly low-grade" occurrences of CRS and neurotoxicity in the KarMMa trial, with "predictable early onset and resolution." CRS of any grade occurred in 85% of patients, with 12 cases of Grade ≥3 CRS, while the rate of CAR-T cell-associated neurotoxicity was 28%.
In the study, cases of prolonged Grade 3 or 4 neutropenia and thrombocytopenia were reported in 41% and 49% of patients, respectively. Three patients underwent stem cell transplant for haematopoietic reconstitution due to prolonged cytopenia, with complications leading to deaths in two of these cases, "which occurred in the setting of ongoing or prior severe CRS or HLH/MAS," the companies said.
Bristol Myers Squibb and bluebird bio last year resubmitted the application for Abecma after the FDA declined to review it and sought more information. The therapy, also referred to as ide-cel and bb2121, is currently under review by regulators in the EU. Bristol Myers Squibb acquired Abecma as part of its $74-billion takeover of Celgene in 2019 and was one of three treatments tied to a contingent values rights payout that ultimately floundered when one of them failed to gain FDA approval by a particular deadline.
For related analysis, see KOL Views Q&A: Expert excitement for CAR-T in multiple myeloma continues to grow.
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