Ten-Year Follow-Up Supports Curative Potential of Tisagenlecleucel in Patients With B-Cell Non-Hodgkin Lymphomas

Clinical Summary: 

• Design/Population: This long-term follow-up assessed outcomes in patients with relapsed or refractory B-cell non-Hodgkin lymphomas treated with a single infusion of the CD19-directed CAR T-cell therapy tisagenlecleucel. 
• Key Outcomes: No relapses occurred beyond 5.4 years, with durable lymphoma-free survival observed at 10 years. Long-term remissions were associated with persistent CAR T-cell activity, and late toxicities were uncommon.
• Clinical Relevance: These findings provide the longest reported follow-up of CD19-directed CAR T-cell therapy and support the potential for long-term disease control in patients with relapsed or refractory B-cell lymphomas.

Long-term follow-up of patients with relapsed or refractory B-cell non-Hodgkin lymphoma demonstrated that tisagenlecleucel induced durable remissions, with no disease relapses occurring 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 study, researchers assessed long-term outcomes in 38 patients, including patients with large B-cell lymphoma (n = 24) and follicular lymphoma (n = 14), who were treated with tisagenlecleucel. The primary end point was lymphoma-free survival. Key secondary end points included progression-free survival (PFS), overall survival (OS), and safety.

At a median follow-up of 10.1 years, no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival rate was 32% in patients with large B-cell lymphoma and 47% in patients with follicular lymphoma. The 10-year PFS rate was 17% in patients with large B-cell lymphoma and 29% in patients with follicular lymphoma, with 10-year OS rates of 17% and 50%, respectively.

Persistent grade 2/3 neutropenia was reported in 5% of patients, and no cases of late anemia or thrombocytopenia were reported. Second primary cancers developed in 9 patients, with a 10-year cumulative incidence of 21%. The 10-year non–relapse-related mortality rate was 18%.

Investigators also observed that greater CAR transgene persistence appeared to be associated with long-term response. Among patients with durable remissions, B-cell aplasia persisted in 44%.

“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