Table 5.

FDA benefit-risk analysis axicabtagene ciloleucel for r/r FL.

Parameter	Summary
Unmet medical need	Patients with relapsed or refractory FL after 2 or more regimens have unmet medical needs.
Clinical Benefit	Of 81 patients in the primary efficacy population, ORR was 91% (95% CI: 83-96) and CR rate 60%, with a 1-year rate of continued remission of 76% (95% CI: 64-85).
Risks	• The USPI for axicabtagene ciloleucel has Warnings and Precautions for CRS, neurological toxicity, serious infections, prolonged cytopenias, hypogammaglobulinemia, and secondary malignancies. • Of 146 patients with iNHL treated with axicabtagene ciloleucel:  ­- ARs in ≥ 30%, excluding laboratory terms, included fever, CRS, hypotension, encephalopathy, fatigue, headache, tachycardia, infections with pathogen unspecified, febrile neutropenia, musculoskeletal pain, nausea, and tremor.  ­- Grade ≥ 3 ARs occurred in 86%; the most common Grade ≥ 3 ARs of interest included febrile neutropenia(41%), prolonged cytopenias (32%), neurological toxicities (21%), infections (16%), and CRS (8%).  - ­Any grade of CRS occurred in 84% patients, neurological toxicity in 77%, serious ARs in 48%, and fatal ARs in 1.4%.
Uncertainties	• Verification of clinical benefit in a confirmatory trial(s) in FL is pending. • Long-term safety after treatment with axicabtagene ciloleucel, particularly for secondary malignancies, is undefined.
Conclusions	• The ZUMA-5 study provides substantial evidence of effectiveness in patients with r/r FL after 2 or more regimens, with an acceptable safety profile. • CRS and neurological toxicity can be life-threatening or fatal, supporting boxed warnings in labeling and a REMS.

Abbreviations: CI, confidence interval; FL, follicular lymphoma; REMS, risk evaluation and mitigation strategy.