Bridging radiotherapy for chimeric antigen receptor T cells therapy in non-Hodgkin lymphoma: Systematic review and meta-analysis.

Abstract

Bridging therapy is often needed for relapsed/refractory non-Hodgkin lymphoma (NHL) receiving chimeric antigen receptor T cells (CART) therapy. Bridging radiotherapy (BRT) is often adopted, but its benefit is uncertain. Here, we performed a systematic review and meta-analysis to study the adoption of BRT in CART therapy. PubMed, MEDLINE and EMBASE were searched until 13 April 2025 for adult NHL studies adopting BRT before CART therapy. Primary endpoints were 1-year overall survival (OS) and progression-free survival (PFS); secondary endpoints were objective response rate (ORR), in-field failure and grade ≥ 3 cytokine-release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Random-effects model was used for pooled estimates. Meta-regression was done to explore clinical covariates. Fifteen studies including 636 patients were reviewed. Pooled 1-year OS was 67 % and 1-year PFS was 52 %. Pooled ORR was 79 % with complete response rate of 57 %. Pooled in-field failure was 11 %. Pooled Grade ≥ 3 CRS was 5 % while Grade ≥ 3 ICANS was 6 %. Bulky, extra-nodal or advanced-stage disease were associated with worse 1-year OS but not with 1-year PFS nor CART toxicity. Comprehensive BRT covering all lesions was associated with improved 1-year PFS and RT doses > 30  Gy EQD2 was associated with 1-year PFS. BRT leads favourable survival outcome and durable local control while maintaining low rate of severe CRS/ICANS. Comprehensive, adequately dosed irradiation may optimise tumour-burden reduction and improve 1-year PFS. Further prospective studies are warranted to refine RT dose, field coverage and patient selection.