On April 1, 2022, axicabtagene ciloleucel was approved for adults with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.1 It is not indicated for the treatment of patients with primary central nervous system lymphoma.
Axicabtagene ciloleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS program.
Supporting Efficacy Data
Approval was based on findings in the open-label phase III ZUMA-7 trial (ClinicalTrials.gov identifier NCT03391466). Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). A total of 359 patients were randomly assigned to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy (n = 180) or second-line standard therapy consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in patients who achieved complete or partial remission (n = 179).
Median event-free survival determined by an independent review committee was 8.3 months (95% confidence interval [CI] = 4.5–15.8 months) with axicabtagene ciloleucel vs 2.0 months (95% CI = 1.6–2.8 months) with standard therapy (hazard ratio = 0.40, 95% CI = 0.31–0.51, P < .0001). The objective response rate was 83% vs 50% (P < .0001).
How It Is Used
The recommended axicabtagene ciloleucel dose is 2 x 106 chimeric antigen receptor (CAR) T cells/kg, with a maximum of 2 x 108 CAR T cells. Product labeling provides instructions on fludarabine/cyclophosphamide lymphodepletion; premedications; and management of cytokine-release syndrome and neurologic toxicities (including the use of tocilizumab and corticosteroids).
In ZUMA-7, the most common adverse events of any grade in the group given axicabtagene ciloleucel were fever (93%), cytokine-release syndrome (92%), fatigue (52%), hypotension (47%), encephalopathy (46%), tachycardia (43%), diarrhea (42%), headache (41%), nausea (40%), and musculoskeletal pain (40%). The most common grade 3 or 4 adverse events were febrile neutropenia (31%), encephalopathy (18%), hypotension (11%), and hypoxia (9%). Grade ≥ 3 cytokine-release syndrome occurred in 7%. Tocilizumab was given to 67% of patients after infusion. The most common grade 3 or 4 laboratory abnormalities were decreased leukocytes, neutrophils, and lymphocytes (94%–95%). Serious adverse events occurred in 50% of patients, most commonly (> 5%) cytokine-release syndrome, fever, encephalopathy, hypotension, infection-unspecified pathogen, and pneumonia. Fatal adverse events occurred in 2% of patients.
Axicabtagene ciloleucel has a boxed warning for cytokine-release syndrome and neurologic toxicities. It also has warnings/precautions for hypersensitivity reactions; serious infections; prolonged cytopenias; hypogammaglobulinemia; secondary malignancies; and effects on the ability to drive and use machines.
1. Yescarta (axicabtagene ciloleucel) suspension for intravenous infusion prescribing information, Kite Pharma, Inc, April 2022. Available at chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.fda.gov/media/108377/download. Accessed May 4, 2022.