3330 - Multi-Institutional Update on Bridging Radiotherapy in Relapsed or Refractory Large B-Cell Lymphoma Patients Prior to CAR T-Cell Therapy

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): We aim to report the outcomes of bridging radiation therapy (RT) compared to other systemic regimens in patients with relapsed/refractory large B cell lymphoma (LBCL) receiving CD19-targeted CAR T-cell therapy. Materials/

Methods: We conducted a multi-institutional retrospective study of patients who received bridging therapies prior to CAR T-cell therapy [RT alone, systemic therapy (ST) alone, or combined modality therapy (CMT)]. Overall survival (OS) and event-free survival (EFS) from the date of CAR T infusion were estimated with the Kaplan-Meier method. In-field response for bridging RT was evaluated using post-CAR T imaging and was analyzed based on the total number of irradiated sites.
Results: A total of 125 patients received bridging therapies (RT alone, 28; CMT, 11; ST alone, 86). The median follow-up after CAR T-cell infusion was 9.2 months. Grade 3 or higher cytokine release syndrome and immune effector cell neurotoxicity syndrome occurred in 5% (n=6) and 24% (n=30), respectively, with no statistically significant differences observed based on the type of bridging therapy. The median OS was 14 months for the RT group, not reached for the CMT group, and not reached for the ST group (p=0.01). The median EFS was 3.5 months for the RT group, 3.0 months for the CMT group, and 4.0 months for the ST group (p=0.9). No statistically significant difference was detected in the duration of response based on the type of bridging therapy (p=0.6). A total of 45 sites were irradiated in 39 patients who received bridging RT pre-CAR T. The median dose/fractionation were 24 Gy (range, 10-37.5 Gy) and 8 fractions (range, 4-15 fractions). The 1-year in-field and out-of-field PFS rates from the RT start date were 82% and 35%, respectively. Only 2 patients experienced grade 3-4 RT-related toxicities. Sixteen patients underwent bridging RT prior to apheresis due to clinical urgency, and they had a lower likelihood of achieving overall response post-CAR T as compared to those who received bridging RT post-apheresis (OR= 0.2, p= 0.04). The median survival among patients who received comprehensive RT was 21.5 months, and for focal RT was 13.1 months (p= 0.1).
Conclusion: Our data supports RT as a bridging strategy for patients with locally progressive LBCL undergoing CAR T-cell therapy, with minimal toxicity and impressive in-field control post-CAR T-cell therapy. Patients who are suitable for comprehensive RT trend towards superior OS compared to focal RT. While our data shows improved outcomes with systemic bridging options, this is likely due to selection bias in choosing bridging regimens given the high local control of RT in a chemo-refractory population. RT dose, fractionation, and field size need to be optimized through further investigation. Research is also needed to explore the use of bridging RT before apheresis, considering factors such as irradiated bone marrow volume and tumor size.