On March 5, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to axicabtagene ciloleucel (Yescarta®) for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

FDA Grants Accelerated Approval to Axicabtagene Ciloleucel for Relapsed or Refractory Follicular Lymphoma

Approval was based on a single-arm, open-label, multicenter trial (ZUMA-5; NCT03105336) that evaluated axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed or refractory FL after two or more lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. Following lymphodepleting chemotherapy, axicabtagene ciloleucel was administered as a single IV infusion.

The main efficacy measures were objective response rate (ORR) and duration of response (DOR) as determined by an independent review committee. Among 81 patients in the primary efficacy analysis, ORR was 91% (95% CI = 83, 96) with a complete remission rate (CRR) of 60% and a median time-to-response of one month. Median DOR was not reached, and the one-year rate of continued remission was 76.2% (95% CI = 63.9, 84.7). For all patients in the trial who received leukapheresis (n = 123), ORR was 89% (95% CI = 83, 94) with a CRR of 62%.

The prescribing information for axicabtagene ciloleucel has a boxed warning for cytokine release syndrome (CRS) and neurologic toxicities. In studies of axicabtagene ciloleucel among all patients with non-Hodgkin’s lymphoma (NHL), CRS occurred in 88% (grade ≥ 3, 10%) and neurologic toxicities occurred in 81% (grade ≥ 3, 26%). The most common non-laboratory adverse reactions (≥ 20%) in patients with NHL were CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, febrile neutropenia, nausea, infections with pathogen unspecified, decreased appetite, chills, diarrhea, tremor, musculoskeletal pain, cough, hypoxia, constipation, vomiting, arrhythmias, and dizziness.

The new prescribing information for axicabtagene ciloleucel will be posted here when available.

FDA gave the indication accelerated approval based on ORR. Continued approval for the indication is contingent on verification and description of clinical benefit in confirmatory trials.

The application was granted priority review, breakthrough designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.