The FDA has now granted accelerated approval to brexucabtagene autoleucel (TecartusTM, Kite Pharma, formerly known as KTE-X19) for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL). Brexucabtagene autoleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, is the first CAR T-cell therapy approved for this rare type of B-cell non-Hodgkin lymphoma.
Efficacy was evaluated in the multicenter, open-label phase 2 ZUMA-2 trial (NCT02601313), which enrolled 74 patients with relapsed/refractory MCL following treatment with up to five previous therapies, including at least one Bruton tyrosine kinase (BTK) inhibitor. Brexucabtagene autoleucel was manufactured for 71 patients and administered to 68 patients. The study's primary end point was the percentage of patients with an objective response per independent radiologic review committee assessment. Following study protocol, the primary efficacy analysis was conducted after 60 patients had been treated and followed for 7 months.
Of the 60 patients in the primary efficacy analysis, 93% experienced an objective response to brexucabtagene autoleucel, including 67% who experienced a complete response. Of the 74 patients in the intention-to-treat population, 85% experienced an objective response, and 59% experienced a complete response. Of the 60 patients in the primary efficacy analysis, 57% were in remission at a median follow-up of 12.3 months, with a 12-month progression-free survival rate of 61% and a 12-month overall survival rate of 83%.
The most frequent adverse events of grade 3 or higher included cytopenias (experienced by 94% of patients), infections (32%), neurologic events (31%), and cytokine release syndrome (CRS) (15%). Additional grade 3/4 adverse events experienced by at least 10% of patients included hypotension, hypophosphatemia, encephalopathy, hypoxia, pyrexia, hyponatremia, hypertension, and hypocalcemia. Two deaths occurred as a result of infectious adverse events. The approval comes with a Risk Evaluation and Mitigation Strategy (REMS) for both CRS and neurologic toxicities, and the prescribing information contains a boxed warning for CRS.
"KTE-X19 [brexucabtagene autoleucel] induced durable remissions in a majority of patients with relapsed or refractory mantle cell lymphoma," concluded the study investigators in their April publication in The New England Journal of Medicine, led by first author Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma and Coleader of the B-Cell Lymphoma Moon Shot at MD Anderson Cancer Center in Houston, Texas. "The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies."
The FDA is requiring the manufacturer of brexucabtagene autoleucel to conduct a post-marketing observational study in order to further evaluate the drug's long-term safety.
The recommended dosage is a single intravenous infusion of 2 x 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 x 108 CAR-positive viable T cells, preceded by fludarabine/cyclophosphamide lymphodepleting chemotherapy.
For More Information
US Food and Drug Administration (2020). FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. Available at: https://www.fda.gov/drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-mantle-cell-lymphomaImage credit: Nephron. Licensed under CC BY-SA 3.0