Safety and Efficacy of Bridging Radiation Therapy in the Context of CD19 CART Therapy for Non-Hodgkin Lymphoma: Systematic Review and Meta-Analysis

Background Bridging radiation therapy (BRT) has been increasingly utilized in the context of CD19 chimeric antigen receptor T-cell (CART) therapy for non-Hodgkin lymphoma (NHL) for disease control and palliation while awaiting CART manufacturing. However, the impact on safety and efficacy remains unknown. Methods We conducted a systematic review and meta-analysis to analyze the safety and the efficacy of BRT and CART19 combination. Our inclusion criteria included studies that enrolled ≥ 5 NHL adult patients who received an FDA-approved CD19 CART product and had been treated with BRT (defined as any radiation exposure between leukapheresis and CART infusion). We excluded conference abstracts and studies that used radiation post-CD19 CART infusion. Endpoints for each study were calculated as proportion of events out of total number of patients. Clopper-Pearson (exact) binomial interval was used to calculate the confidence interval of the rate for individual studies. The rates were transformed with Freeman-Tukey Double arcsine transformation (PFT) method before pooling. Inverse variance (V) weighting method with random effect was used for pooling the effect sizes. All analyses were performed in RStudio with R 4.2.1. Results Our initial literature search identified 778 citations. Of these, 193 abstracts were screened and removed as they were duplicates. Of the 585 abstracts remaining, 523 were screened, and rejected due to patient number, non-FDA approved CART product, conference abstract, or insufficient data. Of the 61 records remaining, 51 full-text articles were excluded for the same reasons and a total of 10 reports were included in our systematic review.A total of 207 patients were included. Diffuse large B-cell lymphoma was the most common histology and axi-cel was the most common CD19 CART product. A significant subset of patients had bulky disease. Full baseline patient and disease-specific characteristics in Table 1. Overall response rate was 77.6% and 40.1% achieved complete response (Figure 1). Progression free survival and overall survival at 1 year were 50.8%, and 70.4%, respectively. All-grade cytokine release syndrome (CRS) was estimated at 83.4% with all-grade immune effector cell-associated neurotoxicity syndrome (ICANS) estimated at 46.4%. Grade 3-4 CRS was estimated at 6.1 % and G 3-4 ICANS estimated at 10.8%. Conclusion Utilizing BRT in the context of CD19 CART appears to be feasible and safe. The lower rates of G 3-4 ICANS in this very high-risk population compared to historic control (28% in Zuma 1 and 21% in Zuma 7) is intriguing and worth further investigation in a prospective sitting. The efficacy of this combination is comparable to pivotal CART trials and real world data. The efficacy data, nevertheless, is promising since significant number of these patients had bulky disease which is historically associated with lower response and high relapse rate.