On April 1, 2022, the FDA accelerated the approval of a new indication for the CAR T-cell therapy axicabtagene ciloleucel (Yescarta; Kite Pharma) for adults with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.
The FDA granted this new indication breakthrough therapy and orphan drug designations.
This new indication was based on a randomized, open-label, multicenter clinical trial of adults with primary refractory large B-cell lymphoma or large B-cell lymphoma that relapses within 12 months after completion of first-line therapy. The patients had not received treatment for relapsed or refractory lymphoma and were candidates for autologous hematopoietic stem-cell transplantation (HSCT).
The study included 359 patients who were randomized in a 1:1 ratio to a single infusion of the CAR T-cell therapy after lymphodepleting chemotherapy or to second-line standard therapy consisting of 2 or 3 cycles of chemoimmunotherapy, followed by high-dose therapy and autologous HSCT in patients achieving complete or partial remission.
The primary efficacy measure was event-free survival (EFS). The EFS was significantly longer in the axicabtagene ciloleucel arm, with a hazard ratio of 0.40 (95% confidence interval [CI], 0.31-0.51; P <.0001). The estimated 18-month EFS rate was 41.5% (95% CI, 34.2-48.6) in the axicabtagene ciloleucel arm and 17% (95% CI, 11.8-23.0) in the standard-therapy arm. The estimated median EFS was 8.3 months and 2.0 months, respectively.
Among patients who received standard therapy, 35% underwent autologous HSCT; lack of response to chemotherapy was the most common reason for not receiving HSCT. The objective response rate was 83% with axicabtagene ciloleucel and 50% with standard therapy, a significant difference.
The most common (≥30%) nonlaboratory adverse reactions reported with axicabtagene ciloleucel were cytokine-release syndrome, fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections with pathogen unspecified, chills, and decreased appetite.
