The U.S. Food and Drug Administration (FDA) granted accelerated approval to brexucabtagene autoleucel (TECARTUS, Kite, a Gilead Company), a CD19-directed genetically modified autologous T cell immunotherapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

Approval was based on ZUMA-2, an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate (ORR) per Lugano [2014] criteria as assessed by an independent review committee.

Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of six months, the ORR was 87% (95% CI: 75, 94), with a complete remission (CR) rate of 62% (95% CI: 48, 74). The estimated median duration of response was not reached (range of 0+ to 29.2+ months) after a median follow-up time for duration of response of 8.6 months. Of all 74 leukapheresed patients, the ORR as assessed by independent review committee (IRC) was 80% (95% CI: 69, 88) with a CR rate of 55% (95% CI: 43, 67).

The most common (≥10%) Grade 3 or higher reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection – pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia. FDA approved brexucabtagene autoleucel with a Risk Evaluation and Mitigation Strategy because of the risk of cytokine release syndrome (CRS) and neurologic toxicities.

The recommended dose of brexucabtagene autoleucel is a single intravenous infusion  of 2 x 106 CAR-positive viable T cells per kg body weight (maximum 2 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.