The Lynx Group

Yescarta First CAR T-Cell Therapy FDA Approved for Patients with Large B-Cell Lymphoma

June 2022, Vol 13, No 3

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.

Related Articles


Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: