5-Year Follow-Up Supports Curative Potential of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma (ZUMA-1). Blood Neelapu, S. S., Jacobson, C. A., Ghobadi, A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., Lin, Y., Braunschweig, I., Hill, B. T., Timmerman, J. M., Deol, A., Reagan, P. M., Stiff, P. J., Flinn, I. W., Farooq, U., Goy, A., McSweeney, P., Munoz, J., Siddiqi, T., Chavez, J. C., Herrera, A. F., Bartlett, N. L., Bot, A. A., Shen, R. R., Dong, J., Singh, K., Miao, H., Kim, J. J., Zheng, Y., Locke, F. L. 2023

Abstract

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we aimed to assess survival and safety in ZUMA-1 after 5 years of follow-up. Eligible adults with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel infusion targeted at 2×106 cells/kg. Investigator-assessed response, updated survival, safety, and pharmacokinetic outcomes were assessed in treated patients. The objective response rate in the 101 treated patients was 83% (58% complete response rate), and with a median follow-up of 63.1 months, responses were ongoing at data cutoff in 31%. Median overall survival (OS) was 25.8 months and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91%. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. ClinicalTrials.gov, number NCT02348216.

View details for DOI 10.1182/blood.2022018893

View details for PubMedID 36821768