Safety and efficacy of autologous humanized CD19 CAR-T cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Chimeric antigen receptor (CAR)-T cells have made great progress in hematological malignancies and optimization of CAR structure is a critical area of exploration. Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). We conducted a clinical trial to determine the safety of hCART19 for patients with R/R B-NHL. Successful infusion of hCART19 were achieved for 26 patients. Twenty-one (80.8%) patients had grade 1-2 cytokine release syndrome (CRS), with only 1 patient having grade 3 CRS. Besides, no immune effector cell-associated neurotoxicity (ICANS) was observed among all the patients. Twenty-one (80.8%) patients achieved an objective response, including 18 (69.2%) complete remission (CR) and 3 (11.5%) partial remission (PR) within 1 month post-infusion. The other 5 patients acquired no response (NR). With a median follow-up time of 20.3 months, 77.8% (14/18) of the CR patients remained CR. The estimated 1-year OS and PFS were 65.8% (95% CI, 49.1% to 88.2%) and 54.8% (95% CI, 38.1% to 78.7%), respectively. CAR-T expansion was observed in all patients (median peak: 220.63 cells/µL). hCART19 demonstrated favorable efficacy and manageable toxicity in R/R B-NHL, providing critical clinical evidence for its clinical application.