Outcomes of Patients Aged 65 Years in ZUMA-1, a Pivotal Phase 1/2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Refractory Large B Cell Lymphoma

Purpose of the Study: Axicel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved by the US Food and Drug Administration for the treatment of patients with relapsed/ refractory LBCL with 2 prior systemic therapies. In the 2-year follow- up of ZUMA-1, the objective response rate (ORR) was 83%, with a complete response (CR) rate of 58%, and 39% of patients in ongoing response (Lancet Oncol. 2019;20:31). The efficacy and safety out- comes of the 2-year follow-up of ZUMA-1 by age 65 and < 65 years will be presented here.

Summarized Description of the Project: In ZUMA-1, eligible patients with refractory LBCL underwent leukapheresis and conditioning chemotherapy followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg. The Phase 2 primary endpoint was investigator-assessed ORR. Additional key endpoints were adverse events (AEs), overall survival (OS), and levels of CAR gene-marked cells in peripheral blood. Efficacy was evaluated for Phase 2 patients; safety was evaluated for all treated patients (Phases 1 and 2). Patients were analyzed by age 65 vs < 65 years.

Results: As of 8/11/2018, 108 patients were treated. There were 27 patients in the 65-year-old subgroup vs 81 patients in the < 65-year-old cohort. Patients had a median age of  69 years and  55 years, respectively. Most (81% and 63%, respectively) were men; 70% vs 36% had an international prognostic index score of 3 to 4; 59% vs 57% had an Eastern Cooperative Oncology Group performance status of 1; 67% vs 72% had 3 prior therapies; and median tumor burdens were 3790 mm2  vs 3574 mm2. Median follow-up was 1 months for patients enrolled in Phase 2 (n = 101). The ORR for patients aged 65 years (n = 24) and < 65 years (n = 77) was 92% and 81% (CR rate, 75% and 53%), respectively, with ongoing responses in 42% and 38% of patients (ongoing CR, 42% and 35%). The 24-month OS rate was 54% for patients aged 65 years and 49% for patients aged < 65 years. Most patients experienced Grade 3 AEs (100% of patients aged 65 years and 98% of patients aged < 65 years). Four percent of each group (1/27 patients aged 65 years and 3/81 patients aged < 65 years) died from AEs as previously reported. Grade 3 neurologic events and cytokine release syndrome occurred in 44% vs 28% and 7% vs 12% of patients aged 65 vs < 65 years, respectively. CAR T cell expansion by peak level (43 vs 35 cells/L) or area under the curve (562  vs  448 days  ×  cells/L)  was  similar  in  patients  aged  65  vs <65 years, respectively.

Conclusion: The 2-year follow-up of ZUMA-1 demonstrates that axi- cel can induce high rates of durable responses with a manageable safety profile for patients aged 65 years and < 65 years. Axi-cel offers substantial clinical benefit for older patients who have refractory LBCL and otherwise have limited treatment options.