We studied the efficacy and safety of the combined treatment with programmed cell death 1 (PD‐1) inhibitors and anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy and subsequent PD‐1 inhibitor maintenance treatment in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) and high tumor burden. Forty‐four R/R DLBCL patients with high tumor burden were enrolled in this study. The experimental group of 26 patients received combined therapy with PD‐1 inhibitors and anti‐CD19‐CAR T cells, while the control group of 18 patients received anti‐CD19‐CAR T‐cell therapy alone. The objective response rate (ORR) was 65.39% and 61.11% in the combination and control groups, respectively. The PD‐1 inhibitor maintenance therapy was selected for patients who achieved complete response or partial response in the combination therapy group. Progression‐free survival and overall survival rates in the combination group were higher than those in the control group 3 and 12 months after CAR T‐cell infusion. There was no significant difference in the grade of cytokine release syndrome or immune effector cell associated neurotoxic syndrome between the two groups. In the maintenance therapy group, only eight patients experienced grade 1 Common Terminology Criteria for Adverse Events (CTCAE) and three grade 2 CTCAE. Overall, we found that the ORR was not affected by the combination therapy with PD‐1 inhibitors and anti‐CD19‐CAR T cells. However, patients who had achieved the ORR might benefit from PD‐1 inhibitor maintenance therapy after combination therapy without increased side effects.

Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem. In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy. We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days. The grades I and II of aGVHD was observed in four patients (36.4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF-α levels increased again in nine of 11 patients after DSI but not in the DLI group. Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.