Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas.
Level 4 - case-series / case-control
Single-arm Phase 2 longitudinal follow-up study without a concurrent comparator
PubMed 42341302 · doi:10.1056/NEJMoa2518035
What was done
Investigators evaluated 10-year clinical outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphoma (24 with large B-cell lymphoma and 14 with follicular lymphoma) treated with CTL019 (tisagenlecleucel), an autologous anti-CD19 CAR T-cell therapy. Measured endpoints included lymphoma-free survival, progression-free survival, overall survival, cumulative incidence of second primary cancers, non-relapse-related mortality, and long-term CAR-transgene persistence through a median follow-up of 10.1 years.
What was found
At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% CI, 14 to 51) for large B-cell lymphoma and 47% (95% CI, 20 to 71) for follicular lymphoma. Ten-year progression-free survival was 17% (95% CI, 5 to 34) for large B-cell lymphoma and 29% (95% CI, 9 to 52) for follicular lymphoma; 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Second primary cancers occurred in 9 patients (10-year cumulative incidence, 21%). Ten-year non-relapse-related mortality was 18% (14% excluding COVID-19). Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%), and B-cell aplasia persisted in 44% of long-term responders.
Why it matters
This study provides evidence that a single infusion of anti-CD19 CAR T-cell therapy can deliver decade-long, potentially curative remissions in relapsed or refractory B-cell lymphomas, with no relapses observed beyond five years.
Limits
The sample size was small (n = 38 total; 24 large B-cell lymphoma, 14 follicular lymphoma), resulting in wide confidence intervals. The study lacked a concurrent comparator arm, and patients experienced high cumulative rates of second primary malignancies (21%) and non-relapse-related mortality (18%).
Cited by
- supports CAR-T cell therapy involves genetically engineering T cells with a synthetic chimeric antigen receptor designed in the lab to target and destroy cancer cells upon reinfusion into a patient.