Multinational phase 2 study of axicabtagene ciloleucel as first-line therapy in high-risk LBCL

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. CAR T-cell therapy is established for the treatment of relapsed/refractory B-cell lymphoma, but its potential when applied as part of first-line therapy for patients at high risk of early chemotherapy failure has not been studied. The multinational phase 2 ZUMA-12 trial evaluated axicabtagene ciloleucel (axi-cel) as part of first-line treatment in 40 patients with high-risk LBCL. The primary outcome was complete response rate. Among 37 efficacy-evaluable patients, the CRR was 78% (95% CI 62-90) and the ORR was 89% (75-97). With median 15.9 months of follow-up 73% of patients remained in objective response; median duration of response, event-free survival, and progression-free survival were not reached. Grade ≥ 3 cytokine release syndrome and neurologic events occurred in 8% and 23%, respectively. There were no treatment-related grade 5 events. The authors conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.