Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas

Author(s): Marco Ruella, M.D.^1,2,3; Luca Paruzzo, M.D.^1,2,3; Emeline R. Chong, B.A.¹; Elise A. Chong, M.D.^1,3; Daniel J. Landsburg, M.D.^1,3; Sunita D. Nasta, M.D.^1,3; Pooja Devi, M.D.⁴; Peter Michener, M.S.²; Federico Stella, M.D.²; Alberto Carturan, M.D.^1,2,3; Ellen B. Napier, C.R.N.P.^1,3; Vivianna M. Van Deerlin, M.D., Ph.D.⁴; Patrizia Porazzi, Ph.D.²; Bruce L. Levine, Ph.D.^2,4; Noelle Frey, M.D.³; David L. Porter, M.D.^2,3; Joseph A. Fraietta, Ph.D.^2,4,5; Jakub Svoboda, M.D.^1,3; Carl H. June, M.D.^2,4; Stephen J. Schuster, M.D.^1,2,3;

Source: NEJMoa2518035

Dr. Maen Hussein's Thoughts

After 10 years one third of the heavily pretreated lymphoma patients who had CAR-T therapy stayed disease free.

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

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.)

Author Affiliations

¹Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia; ²Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia; ³Department of Medicine, Division of Hematology–Oncology, Hospital of the University of Pennsylvania, Philadelphia; ⁴Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia; ⁵Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia

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