In the long-term follow-up to a phase II study published in The New England Journal of Medicine, Ruella et al found that a single infusion of the CD19-directed chimeric antigen receptor (CAR) T-cell therapy CTL019 (now called tisagenlecleucel) produced decade-long remissions in a subset of patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
Study Details
A total of 38 patients (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) were treated with tisagenlecleucel from January 2014 to September 2019, with a data cutoff of October 2025 for the long-term follow-up. The investigators assessed lymphoma-free survival, progression-free survival, overall survival, duration of response, late toxicities, immune reconstitution, and CAR T-cell persistence. Patients remaining in continuous complete remission for at least 5.5 years without additional therapy were classified as long-term responders.
Key Findings
At a median follow-up of 10.1 years (range = 7.9–11.5 years), no relapses had occurred beyond 5.4 years. Overall, 12 of 38 treated patients (31.6%) achieved a long-term response. At 10 years, lymphoma-free survival was 32% (95% confidence interval [CI] = 14%–51%) among patients with large B-cell lymphoma and 47% (95% CI = 20%–70%) among those with follicular lymphoma. Progression-free survival was 17% (95% CI = 5%–34%) and 29% (95% CI = 9%–52%), respectively, whereas overall survival was 17% (95% CI = 5%–34%) and 50% (95% CI = 23%–72%).
Among responders, the estimated duration of response at 10 years was 54% (95% CI = 25%–77%) for those with large B-cell lymphoma and 60% (95% CI = 25%–83%) for those with follicular lymphoma. No relapses occurred beyond 5.4 years overall or beyond 2.7 years among patients with follicular lymphoma.
Persistent grade 2 or 3 neutropenia occurred in two patients; no chronic anemia or thrombocytopenia was observed. Nine patients developed a second primary malignancy, corresponding to a 10-year cumulative incidence of 21% (95% CI = 8%–34%). No CAR T-cell–related lymphomas were identified, and the cumulative incidence of nonrelapse-related mortality at 10 years was 18%.
The investigators concluded: “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.”
Marco Ruella, MD, and Stephen J. Schuster, MD, of Perelman School of Medicine, the University of Pennsylvania, Philadelphia, are the corresponding authors for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others. For full disclosures of the study authors, visit nejm.org.
