Five-Year Follow-Up: Tandem CD19/CD20 CAR T Therapy Enduring Impact on Refractory/Relapsed Non-Hodgkin Lymphoma

In this single-arm, single-center, registrational phase 2 trial, tandem CD19/CD20 chimeric antigen receptor (CAR) T cell (TanCAR7) therapy showed promising efficacy and safety in patients with relapsed/refractory non-Hodgkin's lymphoma (r/r NHL). Here, we report 5-year follow-up results, including assessments of durable response, survival, and safety. We also investigated risk factors and biomarkers associated with treatment resistance or relapse and evaluated salvage therapies after CAR-T cell failure. Among 87 patients with r/r NHL treated with TanCAR7, the objective response rate was 78% (complete remission rate, 70%) with a median follow-up of 63.4 months. At data cut-off, 40% of patients remained in remission. Median overall survival (OS) was not reached, with an estimated 5-year OS rate of 60.1% and median progression-free survival (PFS) of 33 months. No new or unexpected TanCAR7-related serious adverse events or deaths were observed. High tumor burden and systemic inflammation were risk factors for resistance and relapse. In addition to CAR-T cell expansion in peripheral blood, high levels of endogenous CD8 + T cells and total lymphocytes after infusion correlated with treatment benefit. Salvage chemotherapy post TanCAR7 failure showed limited efficacy, whereas targeted therapy or secondary CAR-T cell therapy achieved clinical responses in a subset of patients. This first-ever 5-year follow-up analysis of a dual-targeted CAR T-cell therapy shows long-term remission potential and no new safety signals in patients with r/r NHL. Trial Registration: ClinicalTrials.gov: NCT03097770.