Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma

Abstract Dual‐targeted chimeric antigen receptor T (CAR‐T) cell is an important strategy to improve the efficacy of CD19 CAR‐T cell against refractory or relapsed B cell non‐Hodgkin lymphoma (R/R B‐NHL). However, durable responses are not achieved in most patients, in part owing CAR‐T cell exhaustion caused by PD‐1/PD‐L1 pathway. We conducted a prospective, single‐arm study of dual‐targeted CD19/22 CAR‐T cell combined with anti‐PD‐1 antibody, tislelizumab, in R/R B‐NHL (NCT04539444). Tislelizumab was administrated on +1 day after patients received infusion of CD19/22 CAR‐T cell. Responses, survival and safety were evaluated. From 1 August 2020 to 30 March 2023, 16 patients were enrolled. The median follow‐up time is 16.0 (range: 5.0–32.0 months) months. Overall response was achieved in 14 of 16 (87.5%) patients, and the complete response (CR) was achieved in 11 of 16 (68.8%) patients. The 1‐year progression‐free survival and overall survival rates were 68.8% and 81.3%, respectively. Of the 14 patients responded, 9 patients maintained their response until the end of follow‐up. Among the 15 out of 16 (93.8%) patients who had extranodal involvement, 14 (93.3%) patients achieved overall response rate with 11 (73.3%) patients achieving CR. Eight (50%) patients experienced cytokine release syndrome. No neurologic adverse events were reported. Gene Ontology‐Biological Process enrichment analysis showed that immune response‐related signaling pathways were enriched in CR patients. Our results suggest that CD19/22 CAR‐T cell combined with tislelizumab elicit a safe and durable response in R/R B‐NHL and may improve the prognosis of those patients.