Abstract
Objective: Despite the remarkable success of chimeric antigen receptor modified T (CAR-T) cell therapy for refractory or relapsed B cell non-Hodgkin lymphoma (R/R B-NHL), high rates of treatment failure and relapse after CAR-T cell therapy are considerable obstacles to overcome. Preclinical models have demonstrated that anti-PD-1 antibody is an attractive option following CAR-T therapy to reverse T cell exhaustion. Thus, we investigated their combination in R/R B-NHL.
Methods: We performed a prospective, single-arm study of CAR-T cell combined with anti-PD-1 antibody treatment in R/R B-NHL (NCT04539444). Anti-PD-1 antibody was administrated on day 1 after patients received sequential infusion of anti-CD19 and anti-CD22 second-generation CAR-T cells, and the efficacy and safety of the combination treatment were evaluated.
Results: From August 1, 2020 to June 30, 2021, a total of 11 patients were enrolled and completed at least 3 months follow-up. The median follow-up time is 5.8 months. Overall response was achieved in 9 of 11 patients (81.8%), and the complete response (CR) was achieved in 8 of 11 patients (72.7%). All 8 patients achieving CR still sustained remission at the last follow-up. The progression-free survival (PFS) and overall survival (OS) rates at 6 months were 80.8% and 100.0%, respectively. Cytokine release syndrome (CRS) occurred in only 4 patients (all were grade 1), and no neurotoxicity were observed.
Conclusion: This study suggests that CAR-T cells combined with anti-PD-1 antibody elicit a safe and durable response in R/R B-NHL.
Keywords: chimeric antigen receptor modified T cell, anti-PD-1 antibody, CD19/CD22, refractory or relapsed B cell non-Hodgkin lymphoma
Disclosures
No relevant conflicts of interest to declare.
OffLabel Disclosure:
We use the T cells were transduced with a lentivirus encoding the CD19-4-1BB-CD3 z and CD22-4-1BB-CD3 ztransgene to produce CAR-T cells. The main purpose of our study is to improve the response rate in patients with R/R B-NHL.
ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgkin lymphoma (NHL)