First CAR T-Cell Therapy for B-Cell Lymphoma Receives FDA Approval

The U.S. Food and Drug Administration (FDA) approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (or KTE-C19) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of therapy, including diffuce large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (FL).

The safety and efficacy of axicabtagene ciloleucel were demonstrated in the ZUMA-1 trial, which included 111 patients (median age = 58 years; range = 23-76 years) with previously treated DLBCL, PMBCL, or transformed FL from 22 institutions. As of the data cutoff date (January 27, 2017), 101 patients (91%) had received axicabtagene ciloleucel 2×106 cells/kg, following conditioning with low-dose cytarabine and fludarabine. The ORR as assessed by independent central review was 72 percent, with a CR rate of 51 percent (95% CI 41-62). The median duration of response was 8.1 months (range not provided) and was not reached for patients who achieved CR. The median OS also was not reached during study follow-up, and the six-month OS rate was 80 percent.

The most common grade ≥3 treatment-related AEs included neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), thrombocytopenia, (24%), and encephalopathy (21%).

The drug carries a boxed warning for cytokine release syndrome (CRS) and neurologic events and was approved with a Risk Evaluation and Mitigation Strategy. In the study, 13 percent and 28 percent of patients experienced severe, grade ≥3 CRS and neurologic events, respectively. Fatal cases of CRS and neurologic toxicity occurred.

In the subset of 70 patients who experienced CRS or neurologic events, 43 required treatment with tocilizumab and 27 required treatment with tocilizumab and steroids, but these treatments did not decrease the efficacy of axicabtagene ciloleucel (ORR=84% and 78%, respectively).

Sources: U.S. Food and Drug Administration news release, October 18, 2017; Kite Pharma news release, October 18, 2017.