FDA approval for axicabtagene ciloleucel as second-line therapy for LBCL patients

April 2022 Clinical trials Nalinee Pathak

Based on the ZUMA-7 clinical study results, the Food and Drug Administration (FDA) has approved the use of axicabtagene ciloleucel (axi-cel) for large B cell lymphoma (LBCL) patients that are unresponsive to first-line chemoimmunotherapy or relapse within one year of first-line chemoimmunotherapy.

A randomised, open-label, multicenter trial enrolled 359 patients with primary refractory LBCL or relapse within 12 months after first-line therapy. None of the patients was treated for relapsed or refractory lymphoma and thus were potential candidates for the study. All the participants were randomised (1:1) to receive axi-cel followed by fludarabine and cyclophosphamide lymphodepleting chemotherapy or standard of care second-line therapy (2 or 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation in patients who attained complete remission or partial remission). The study’s primary endpoint was event-free survival (EFS), determined by an independent review committee (IRC).

Main findings of the ZUMA-7 trial

The estimated 18-month EFS rate was higher in the axi-cel arm (41.5% , 95% CI: 34.2, 48.6) than the standard therapy group (17.0%, 95% CI: 11.8, 23.0). The estimated median PFS too was prolonged with axi-cel (8.3 months, 95% CI: 4.5, 15.8) versus the standard therapy arm (2. o months, 95% CI: 1.6, 2.8). Also, the IRC-assessed best objective response rate was 83% (95% CI: 77, 88) in the axi-cel arm compared to the control arm (50%, 95% CI: 43, 58).

The recommended dose for the use of axi-cel is 2 x 106 chimeric antigen receptor (CAR)-positive, viable T cells per kg of body weight, with a maximum of 2 x 108 CAR-positive viable T cells. The prescription warns of cytokine release syndrome (CRS) and neurologic toxicities. Studies in patients with non-Hodgkin lymphoma have reported CRS and neurological toxicities in 90% and 78% of patients treated with axi-cel. The most common adverse reactions (incidence ≥30%) are CRS, fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhoea, musculoskeletal pain, infections with pathogen unspecified, chills, and decreased appetite.