Ten-Year Follow-Up Supports Curative Potential of Tisagenlecleucel in Patients With B-Cell Non-Hodgkin Lymphomas
Clinical Summary:
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Design/Population: This long-term follow-up evaluated patients with relapsed or refractory B-cell non-Hodgkin lymphoma treated with a single infusion of the CD19-directed CAR T-cell therapy tisagenlecleucel.
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Key Outcomes: No disease relapses occurred beyond 5.4 years after treatment, with durable lymphoma-free survival maintained at 10 years. Long-term remissions were associated with persistent CAR T-cell activity, and late treatment-related toxicities were uncommon.
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Clinical Relevance: These findings represent the longest reported follow-up of CD19-directed CAR T-cell therapy and support its potential to achieve durable long-term disease control in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
The longest reported follow-up of CD19-directed CAR T-cell therapy demonstrated that a single infusion of tisagenlecleucel produced durable long-term remissions in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with no disease relapses observed beyond 5.4 years after treatment.
“Anti-CD19 CAR T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas… [However] long-term results and curative potential remain uncertain,” stated Marco Ruella, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, and coauthors.
In this long-term follow-up study, investigators evaluated outcomes in 38 patients, including 24 with large B-cell lymphoma and 14 with follicular lymphoma, who received a single infusion of tisagenlecleucel. The primary end point was lymphoma-free survival. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.
After a median follow-up of 10.1 years, no relapses were observed beyond 5.4 years following CAR T-cell infusion. The 10-year lymphoma-free survival rate was 32% among patients with large B-cell lymphoma and 47% among those with follicular lymphoma. Corresponding 10-year PFS rates were 17% and 29%, respectively, while 10-year OS rates were 17% and 50%.
Late treatment-related toxicities were uncommon. Persistent grade 2/3 neutropenia occurred in 5% of patients, and no cases of late anemia or thrombocytopenia were reported. Second primary malignancies developed in 9 patients, corresponding to a cumulative 10-year incidence of 21%, and the 10-year nonrelapse mortality rate was 18%.
Investigators also found that prolonged CAR T-cell persistence appeared to be associated with durable clinical benefit. Among patients with long-term remissions, B-cell aplasia persisted in 44%, consistent with sustained CAR T-cell activity.
“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,” concluded Dr Ruella et al.
Source:
Ruella M, Paruzzo L, Chong ER, et al. Ten-year outcomes after CAR T-cell therapy for B-cell lymphomas. N Engl J Med. Published online: June 24, 2026. doi: 10.1056/NEJMoa2518035
