On July 24, 2020, the FDA announced the accelerated approval of brexucabtagene autoleucel (Tecartus), previously recognized as KTE-X19. This agent is the first and only chimeric antigen receptor (CAR) T-cell therapy indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). Brexucabtagene autoleucel is classified as a CD19-directed genetically modified autologous T-cell immunotherapy and is available as a cell suspension for infusion. The approval of this one-time therapy follows a priority review and FDA breakthrough therapy designation. 

The approval of this novel agent was based on the efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy, and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint was objective response rate (ORR) per the Lugano Classification (2014), characterized as the combined rate of complete response (CR) and partial responses as evaluated by an Independent Radiologic Review Committee. In the study, 87% of patients (n = 60 evaluable for efficacy analysis) responded to a single infusion of brexucabtagene autoleucel, including 62% of patients who attained a CR. Among all patients, follow-up was at least 6 months after their first objective disease response. Average duration of response has not yet been achieved. 

With regard to adverse events, 18% of the 82 patients evaluable for safety experienced >grade 3 cytokine release syndrome and 37% experienced neurologic events. The most frequent (≥10%) grade 3 or higher adverse reactions noted were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia. Brexucabtagene autoleucel also has a boxed warning related to cytokine release syndrome (CRS) and neurologic toxicities. The manufacturer recommends that patients should be monitored daily for at least 7 days at the certified healthcare facility and for 4 weeks following infusion for signs and symptoms of CRS and neurologic toxicities and treated immediately. 

Additionally, the FDA approved brexucabtagene autoleucel with a risk evaluation and mitigation strategy (REMS). The brexucabtagene autoleucel REMS has been combined with the axicabtagene ciloleucel (Yescarta) REMS and is now called the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program.” The REMS program is intended to update and educate healthcare professionals about the risks related with the usage of brexucabtagene autoleucel therapy, and training and certification on the REMS program will be an indispensable part of the final authorization for centers utilizing brexucabtagene autoleucel. Further information about the REMS program can be found at www.YescartaTecartusREMS.com.

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