Sequential PD-1 inhibitors as consolidative therapy post-CD19 CART in relapsed/refractory NHL: a propensity score matching cohort study.

BACKGROUND: CD19-directed chimeric antigen receptor T-cell therapy (CART) has improved outcomes for relapsed/refractory non-Hodgkin lymphoma (R/R NHL). However, patients with high-risk molecular features, such as double-expressor lymphoma (DEL+), characterized by concurrent MYC and BCL-2 protein overexpression, and TP53 alterations (TP53+), experience dismal outcomes with CART alone. METHODS: This single-center, propensity score matching (PSM) cohort study analyzed 44 R/R NHL patients. 22 patients received consolidative PD-1 inhibitors (Sintilimab, iPD-1) after CART, matched 1:1 with 22 patients receiving CART alone based on 10 baseline characteristics. RESULTS: The CART + iPD-1 group showed significantly improved progression-free survival (PFS, median 42.9 months vs. 3.0 months; HR = 0.32, P = 0.003) and overall survival (OS, median not reached vs. 21.5 months; HR = 0.24, P = 0.017). Disease recurrence (40.9% vs. 81.8%, P = 0.013) and progression-related mortality (13.6% vs. 54.5%, P = 0.011) were markedly reduced. The DEL+TP53+ subgroup benefited most (PFS P < 0.001, OS P = 0.010). Adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were comparable between groups. CONCLUSION: Consolidative PD-1 inhibitors following CD19 CART infusion could improves survival outcomes in R/R NHL, particularly for the high-risk DEL+TP53+ population, without adding significant toxicity. This suggests a molecularly-defined approach to consolidation therapy and emphasizes the importance of strategic timing in combination immunotherapy.