Radiotherapy as a Bridging Approach in High-Grade B-Cell Lymphomas before CD19-Targeted CAR T-Cell Therapy

Abstract

<h3>Purpose/Objective(s)</h3> To evaluate the safety and efficacy of bridging radiation therapy (RT) in patients with relapsed/refractory high-grade B cell lymphomas (HGBCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. <h3>Materials/Methods</h3> A multi-institutional retrospective study was performed for 352 patients with HGBCL treated with CAR T-cell therapy. 140 of 352 patients (40%) received bridging therapy prior to CAR T infusion: systemic therapy alone in 98 patients, and RT +/- systemic therapy in 42 patients. This report focuses on the outcome of the 42 patients who received bridging RT. Overall survival (OS) from the date of CAR T infusion was estimated with the Kaplan-Meier method. The time to in-field progression was defined as the time from the start date of bridging RT until the time of in-field progression. <h3>Results</h3> The median follow-up from the date of CAR T infusion was 5.2 months (range, 9 days-33.6 months). Thirty-four patients (81%) received RT within 30 days of CAR T infusion, while 8 patients (19%) received RT at least 30 days before infusion. The most common indication for bridging RT was symptomatic local progression, with 16 patients starting RT prior to apheresis due to clinical urgency. Sites of RT include: head and neck (12), central nervous system (8), chest (5), pelvis (5), abdomen (4), extremities (2), paraspinal area (3), and multiple sites (3). The median dose/fractionation were 24 Gy (range, 8-37.5 Gy) and 8 fractions (range, 2-15 fractions). Three patients (7%) had in-field progression at a median time of 3.2 months (range, 1.2-4.6 months), all of whom had bulky disease (≥5 cm) at the time of apheresis. Superior median OS was observed among the 38 patients (90%) who achieved objective in-field responses after bridging-RT (25.6 months vs. 2.1 months; p=<0.001). Only 2 patients experienced grade 3-4 RT-related toxicities. <h3>Conclusion</h3> Our data supports that RT is an effective bridging approach for patients with locally progressive HGBCL prior to CAR T-cell therapy. It is associated with limited toxicity, and offers excellent in-field control in the immediate post-CAR T timeframe. Patients with in-field response to bridging RT have significantly better survival outcome.