205 - Multi-Institutional Update on Salvage Radiation Therapy in Relapsed/Refractory Large B Cell Lymphoma Patients in Post-CAR T Cell Therapy Failure

H. Ababneh¹, A. K. Ng², M. J. Frigault³, C. Jacobson⁴, and C. G. Patel¹; ¹Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ²Dana Farber Cancer Institute, Boston, MA, ³Massachusetts General Hospital/ Harvard Medical School, Boston, MA, ⁴Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Purpose/Objective(s): To assess the long-term outcomes of salvage radiation therapy (RT) compared to other therapeutic approaches for patients with relapsed/refractory large B-cell lymphoma (LBCL) after CD19-targeted chimeric antigen receptor (CAR T)-cell therapy failure. Materials/

Methods: We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy and received salvage therapies [RT alone, systemic therapy (ST) alone, or combined modality therapy (CMT)]. All three categories were defined at the time of the first salvage therapy following CAR T-cell therapy failure. A separate analysis was then conducted for patients who were treated with comprehensive versus focal RT; only the first RT course was included in this analysis for patients receiving >1 salvage RT course. In-field response for salvage RT was evaluated using post-RT imaging and/or clinical assessment.
Results: A total of 128 patients with post-CAR T relapsed LBCL received salvage therapies (RT, 24 patients; CMT, 16 patients; ST, 88 patients). The median follow-up after CAR T-cell infusion was 14.2 months [interquartile range (IQR): 6.3-40.5 months], and the median follow-up after post-CAR T salvage therapy was 7 months (IQR: 2.6-23.8 months). Analysis of patterns of failure revealed that the majority of patients (n=96, 75%) had a component of failure in previously involved sites pre-CAR T. There was no statistically significant difference in overall survival (OS) and event-free survival (EFS) based on the type of salvage therapy. A total of 101 sites were irradiated in 55 patients who received any salvage RT post-CAR T failure. The median dose/fractionation were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The median in-field PFS was not reached (95% CI: 29.5 months – not reached) and out-of-field PFS was 2.6 months (95% CI: 1.7 months – 7.5 months). The 3-year in-field PFS was 62%. Seventeen sites experienced local recurrence with a median time to in-field progression of 3.5 months (IQR: 2.4-9.8 months). There was a non-significant trend of higher in-field PFS for sites that received high-dose RT (BED₁₀= 39 Gy) as compared to sites that received low-dose RT (BED₁₀<39 Gy) (median in-field PFS: not reached vs. 11.4 months, log-rank p= 0.09). The 2-year OS and PFS rates for patients who received comprehensive RT (n=30) vs. focal RT (n=25) were 55% vs. 10% (p<0.0001), and 36% vs. 5% (p=0.001), respectively.
Conclusion: Salvage RT can provide impressive in-field control after CAR T-cell therapy failure. Patients suitable for comprehensive RT exhibit superior OS compared to those receiving focal RT. Analysis of the dose-response relationship may be limited by the number of local failures and selection bias; therefore, larger cohorts are needed to confirm our findings.