Radiotherapy Combined Chimeric Antigen Receptor T-Cells Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma（R/R DLBCL）

Abstract

Background: CAR (chimeric antigen receptor) T-cell therapy has transformed the treatment of patients with recurrent or refractory hematological malignancies. However, some patients cannot benefit from CAR-T cell therapy. Radiation therapy (RT) can induce immune effects and has synergistic effects in combination with other treatments. With the help of RT's immunomodulatory effects, a successful bridging strategy can be developed. This study aimed to investigate the efficacy and safety of CAR-T combined radiotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Methods: We retrospectively analyzed the clinical data of 57 R/R DLBCL patients who received radiotherapy combined CAR-T therapy in Tongji Hospital of Tongji University between January 2018 and February 2023 (NCT02537977). 18 Patients (31.58%) received radiation therapy within 1 year before CAR-T therapy and 1 patient (1.75%) received radiation therapy 1 month later after CAR-T therapy. Patients were divided into two groups: CART group and CAR-T+RT group. Clinical features, treatment response and incidence of adverse events of 57 patients were collected and analyzed to demonstrate the efficacy of CAR-T combined radiotherapy in patients with R/R DLBCL. Results: Of the 57 patients with R/R DLBCL treated with CAR-T therapy, 19 patients (33.33%) received CAR-T combined radiotherapy. The overall response rate (ORR) is 63.00% and 35.80% for patients in CAR-T+RT group and CAR-T group, respectively. The response rate is better for patients in CAR-T+RT group than that of CAR-T group P=0.05). One-year overall survival (OS) is 72.40% (95%CI, 61.90-82.90% ) for patients in CAR-T+RT group, while 1-year OS is 47.40% (95%CI, 39.30-55.50%) for patients in CAR-T group. The median progression-free survival (PFS) is 91 days (95%CI, 35.12-146.88) for patients in CAR-T group and the median PFS is not reached for patients in CAR-T+RT group. There is significantly different in OS and PFS for patients in CAR-T+RT group and CAR-T group ( P=0.02 and P=0.01). Only one patient with CNS lymphoma developed grade 4 CRES. 9 patients (47.37%) occurred grade 1-2 CRS, no patient occurred ≥grade 3 CRS for patients in CAR-T+RT group; 2 patients (3.51%) occurred grade 3 CRS, 25 patients (65.80%) occurred grade 1-2 CRS, no patient occurred grade 4-5 CRS for patients in CAR-T+RT group. Conclusion ： Our study shows that CAR-T combined radiation therapy can obtained better remission rate for R/R DLBCL patients. It is also can effectively prolong PFS and OS, improving the survival of patients. Radiotherapy combined with CAR-T therapy showed efficacy and manageable tolerability, making it a promising treatment option for patients with R/R DLBCL.