Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 10<sup>6</sup> CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment and overall survival were not reached (NR). At data cutoff, 55% of patients were alive without requiring subsequent anticancer therapy. Median lymphoma-specific PFS in patients with FL was NR; 34% had progression or death due to lymphoma or study treatment. Notably, after 30 months postinfusion, progression or lymphoma-related deaths were rare. Late-onset toxicities were infrequent and largely unrelated to axi-cel. Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL.
Authors
- Lori Ann Leslie (ORCID: https://orcid.org/0000-0002-7265-4076)
- Matthew L. Ulrickson (ORCID: https://orcid.org/0000-0002-1458-7813)
- Olga Nikolajeva (ORCID: https://orcid.org/0000-0001-9910-6857)
- David G. Maloney (ORCID: https://orcid.org/0000-0002-8477-6919)
- Soumya Poddar (ORCID: https://orcid.org/0000-0002-9758-8722)
- Caron Alyce Jacobson (ORCID: https://orcid.org/0000-0002-0180-0654)
- Olalekan O. Oluwole (ORCID: https://orcid.org/0000-0001-8525-9641)
- Jacob Wulff (ORCID: https://orcid.org/0000-0003-4584-922X)
- Alison R. Sehgal (ORCID: https://orcid.org/0000-0003-3954-7401)
- Ibrahim Yakoub‐Agha (ORCID: https://orcid.org/0000-0003-4524-8782)
- Emmanuel Bachy (ORCID: https://orcid.org/0000-0003-2694-7510)
- Pashna N. Munshi (ORCID: https://orcid.org/0000-0002-8079-9443)
- Rashmi Khanal
- Joseph D. Rosenblatt (ORCID: https://orcid.org/0000-0003-0798-0403)
- Sattva Swarup Neelapu (ORCID: https://orcid.org/0000-0003-1045-4914)
- Rhine R. Shen (ORCID: https://orcid.org/0009-0000-8883-0727)
- Sven de Vos (ORCID: https://orcid.org/0000-0002-6715-4851)
- Julio C. Chávez (ORCID: https://orcid.org/0000-0002-2045-6238)
- Ran Reshef (ORCID: https://orcid.org/0000-0003-2185-9546)
- Narendranath Epperla (ORCID: https://orcid.org/0000-0002-8216-3457)
- Wangshu Zhang (ORCID: https://orcid.org/0000-0003-2688-5399)
- Carla Casulo (ORCID: https://orcid.org/0000-0001-9993-5065)
- Harry Miao (ORCID: https://orcid.org/0009-0003-7480-7405)
Institutions
- Fox Chase Cancer Center (US)
- Hackensack University Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Miami (US)
- Inserm (FR)
- Université de Lille (FR)
- Columbia University Irving Medical Center (US)
- Ronald Reagan UCLA Medical Center (US)
- University of Rochester Medical Center (US)
- Centre Hospitalier Universitaire de Lille (FR)
- Moffitt Cancer Center (US)
- Fred Hutch Cancer Center (US)
- Los Angeles Medical Center (US)
- Hôpital Lyon Sud (FR)
- Dana-Farber Cancer Institute (US)
- UPMC Hillman Cancer Center (US)
- Sylvester Comprehensive Cancer Center (US)
- Banner MD Anderson Cancer Center
- Herbert Irving Comprehensive Cancer Center
- The Ohio State University (US)
- University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Journal of Clinical Oncology
- Published
- 2025-10-16
- DOI
- https://doi.org/10.1200/jco-25-00668
- Citations
- 4
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 4.18