202 - Bridging Radiotherapy for Patients with Limited (<5 Disease Sites) Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma prior to CAR T-Cell Therapy

O. Saifi¹, W. Breen², S. C. Lester², W. G. Rule³, B. J. Stish², A. Rosenthal⁴, J. Munoz⁴, Y. Lin⁵, P. Johnston⁵, S. M. Ansell⁵, J. Paludo⁵, A. Khurana⁵, J. Villasboas Bisneto⁵, Y. Wang⁵, M. Iqbal⁶, M. Alhaj Moustafa⁶, H. S. Murthy⁶, M. Kharfan-Dabaja⁶, B. S. Hoppe¹, and J. L. Peterson¹; ¹Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, ²Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ³Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, ⁴Division of Hematology, Mayo Clinic, Phoenix, AZ, ⁵Division of Hematology, Mayo Clinic, Rochester, MN, ⁶Division of Hematology, Mayo Clinic, Jacksonville, FL

Purpose/Objective(s): Unirradiated relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) patients who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized pre-CART disease. This study is the first to report on the role of bridging radiotherapy (BRT) for patients with limited (<5 involved sites) disease prior to CART. Materials/

Methods: Following Institutional Review Board approval, a retrospective review from 2018 to 2023 across 3 centers was performed and identified 150 patients with r/r B-cell NHL who received CART and had <5 disease sites prior to leukapheresis. Ann Arbor staging was used to define the number of involved disease sites. Bridging treatment (radiation and/or systemic therapy) was defined as treatment administered between leukapheresis and CART infusion. Bridging radiation (BRT) was defined as comprehensive, treating all PET-avid disease sites, or focal. Local relapse was defined as disease recurring at the same site(s) (with or without new sites) on PET imaging prior to CART infusion. Relapse-free survival (RFS) was defined from CART infusion to any disease relapse/progression. Event-free survival (EFS) was defined from CART infusion to any disease relapse/progression, initiation of post-CART consolidative/salvage therapy, or death.
Results: Prior to CART infusion, 48 (32%) patients received BRT and 102 (68%) did not. The median number of involved disease sites prior to leukapheresis was 2 (range: 1-4). Female gender and extranodal involvement were more common in the BRT group. The median equivalent 2 Gy BRT dose was 25.5 (range: 9.3-43) Gy. There were no grade =3 BRT-related toxicities. The median follow-up was 21 months. Following CART infusion, BRT patients had better objective response rate (92% vs 78%, p=0.046). Sustained complete response without subsequent relapse was higher with BRT (54% vs 33%, p=0.016). Local relapse in sites present prior to CART was lower in the BRT group (21% vs. 46%, p=0.003). BRT patients had improved 2-year RFS (53% vs 44%, p=0.023) and 2-year EFS (37% vs 34%, p=0.039) compared to no BRT patients. Further improvement in 2-year RFS (57% vs 44%, p=0.003) and 2-year EFS (44% vs 32%, p=0.008) was seen in patients who received comprehensive BRT to all active disease sites (n=37) compared to those who did not (n=113). The impact of BRT was most prominent in patients who had =2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared to 42% in those who did not (p=0.002). This improvement in RFS was not seen in patients who had >2 pre-CART involved disease sites.
Conclusion: BRT prior to CART for patients with limited (<5 involved disease sites) r/r NHL improves response rate, local control, RFS, and EFS without causing significant toxicities. Larger prospective studies are needed to confirm our findings, and clinical predictors of which patients will benefit most from BRT are needed.