Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas
Published June 24, 2026
N Engl J Med 2026;394:2440-2448
DOI: 10.1056/NEJMoa2518035
Abstract
Background
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain.
Methods
We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) — autologous T cells expressing CD19-directed, 4-1BB–costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non–relapse-related death and second primary cancer was estimated with the Aalen–Johansen method. The data-cutoff date was October 1, 2025.
Results
At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non–relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response.
Conclusions
Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.)
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Notes
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by the Richard Berman Family Innovations Center in CLL and Lymphomas (to Stephen J. Schuster), the Maguire Family Fund for Lymphoma Research (to Stephen J. Schuster), the Laffey-McHugh Foundation (to Jakub Svoboda), and a National Cancer Institute Research Program Project Grant (P01 CA214278, to Marco Ruella and Carl H. June). The original study was supported by Novartis and a grant from the National Institutes of Health (1R01CA165206, to Carl H. June).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank all the patients and their families, as well as the clinical research and nursing teams at the Abramson Cancer Center of the University of Pennsylvania.
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History
Published online: June 24, 2026
Published in issue: June 25, 2026
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