Safety and efficacy of bridging radiation therapy prior to CD19 CAR T for non-Hodgkin lymphoma: a systematic review and meta-analysis

Bridging radiation therapy (BRT) is increasingly utilized prior to CD19-directed chimeric antigen receptor T cells (CART19) in patients with non-Hodgkin lymphoma (NHL). However, its impact on outcomes of CART19 therapy is not established. We conducted a systematic review and meta-analysis to estimate the safety and efficacy of BRT prior to CART19 therapy. A comprehensive search was performed in databases from inception to October 2024. We identified 18 studies encompassing 538 adult NHL patients who received BRT prior to commercial CART19. Random-effect models were applied to explore meta-analysis outcomes. Diffuse large B-cell lymphoma was the most common diagnosis (73%), and axicabtagene ciloleucel was the most utilized product (67%). Bulky disease was present in 37%. The median dose of BRT was 30 Gy delivered comprehensively to all sites of positron emission tomography-avid disease in 76% of cases. The overall response rate to CART19 was 78.9%. At 1 year, the progression-free survival was 54.6% while overall survival was 71.2%. All-grade cytokine release syndrome (CRS) developed in 80% of cases while all-grade immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 39.4%. The rate of grade 3/4 CRS was 3.6%, while that of grade 3/4 ICANS was 10.6%. Sensitivity analyses including studies with bulky disease and excluding studies with patients who also received systemic bridging therapy, demonstrated consistent results compared to the main study findings. Subgroup meta-regression showed similar results in studies that utilized BRT only compared to studies that utilized combined-modality treatment. In conclusion, this meta-analysis found that BRT use prior to CART19, whether as a standalone approach or in combination with systemic therapy, does not increase toxicity or compromise the efficacy of CART19 therapy in NHL. Furthermore, the use of BRT is associated with a low rate of CRS, even in patients with bulky disease.