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.
Axicabtagene ciloleucel is not indicated for patients with primary central nervous system lymphoma.
“Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory LBCL [large B-cell lymphoma] are treated moving forward. Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR T-cell therapy authorized treatment center for evaluation,” Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator and Associate Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, said in a press release.
This new indication was based on the ZUMA-7 study, 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 transplant (HSCT).
The study included 359 patients who were randomized (1:1) 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 the patients who received standard therapy, 35% had undergone 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 are cytokine-release syndrome, fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections with pathogen unspecified, chills, and decreased appetite.