Combining CAR-T therapy with radiotherapy or not in refractory/relapsed diffuse large B-cell lymphoma: A comparative study

Abstract

Background

Radiotherapy and Chimeric Antigen Receptor(CAR)-T therapy may exhibit a synergistic effect, suggesting that incorporating radiotherapy into CAR-T could improve the prognosis for patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DCBCL). A lack of standardized treatment protocols and relevant guidelines in bridging radiotherapy(BRT) prior to CAR-T therapy still exists. Consequently, we retrospectively analyzed the outcomes of R/R DLBCL patients treated with BRT prior to CAR-T therapy or not, aiming to evaluate the efficacy and satety of BRT as well as the impact of radiotherapy dose on prognosis.

Methods

Between December 2017 and January 2025, 80 patients diagnosed with R/R DLBCL were treated with CAR-T. Thirty-five of them received BRT during leukapheresis and lymphodepletion. The primary endpoint of this study was progression free survival(PFS), and secondary endpoints included overall survival(OS), disease-specific survival(DSS), in-field PFS, best objective response rate(ORR), and complete response rate(CRR). PFS and OS of CAR-T were compared between BRT group and no BRT group. In the subgroup of radiotherapy patients, PFS, OS and in-field PFS were compared between the low-Equivalent dose to 2 Gy per fraction(EQD₂) subgroup and the high-EQD₂ subgroup.

Results

BRT group showed obviously longer PFS and OS than no BRT group(p = 0.001, p = 0.043). In addition, BRT did not increase the incidence of CAR-T toxicities during follow-up (median:35.27 months). Comprehensive BRT subgroup improved prognosis in PFS(p = 0.015) and OS(p = 0.029) when compared with focal BRT subgroup, no significant effect on DSS was noted(p = 0.109). High-EQD2 subgroup did not significantly improve PFS(p = 0.181) and OS(p = 0.665) except for local control(p = 0.079) especially in patients with high tumor burden(p = 0.005). There is no impact on prognosis between early salvage radiotherapy(SRT) and salvage chemotherapy(SCT) cohorts in patients with PR response to CAR-T therapy.

Conclusions

Our analysis demonstrated that BRT is a effective and safe approach for patients with R/R DLBCL preparing for CAR T-cell therapy, which indicated that BRT may enhance the anti-tumor effect of CAR T-cells.