Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study

Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study

Abstract: Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (BCLs) who received Br-RT f...

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Main Authors: Nikhil Yegya-Raman, John P. Plastaras, Christopher M. Wright, Monica Chelius, Siqi Zhang, Jonathan A. Baron, Harper Hubbeling, Austin J. Sim, Timothy J. Robinson, Michael D. Jain, Brandon Imber, Beatrice Fregonese, Joachim Yahalom, Colton Ladbury, Savita Dandapani, Chelsea C. Pinnix, Jillian R. Gunther, Penny Q. Fang, Susan Y. Wu, Bouthaina S. Dabaja, Joanna C. Yang, Jessica Chew, Steve Braunstein, Sumi Sinha, Nathan M. Delinger, Susan Sun, Stephanie A. Terezakis, Gukan Sakthivel, Louis S. Constine, Amit K. Chowdhry, Patrick M. Reagan, Skyler Burke, Yolanda D. Tseng, Michael J. LaRiviere, Amit Maity, Stephen J. Schuster, Elise A. Chong, Nicholas B. Figura
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925002186
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Summary:Abstract: Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (BCLs) who received Br-RT followed by CAR-T from 2018 to 2020 across 10 institutions. Br-RT toxicities were graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy Consensus Guidelines. One hundred seventy-two patients (168 large BCL) received Br-RT before axicabtagene ciloleucel (73%), tisagenlecleucel (24%), or brexucabtagene autoleucel (2%). At leukapheresis, most patients (74%) had advanced-stage disease and 39% had bulky disease measuring ≥10cm. Comprehensive Br-RT was administered to 39% and bridging systemic therapy to 35%. Among all patients, grade ≥3 Br-RT toxicity occurred in 2% (1 grade 5 toxicity), grade ≥3 CRS in 9%, and grade ≥3 ICANS in 24%. Median follow-up was 31.3 months. Two-year progression-free survival (PFS) and overall survival (OS) were 38% and 53%, respectively. On multivariable analysis, comprehensive Br-RT was associated with superior PFS (hazard ratio [HR], 0.38; P < .001) and OS (HR, 0.48; P = .011). Patients with lactate dehydrogenase (LDH) normalization after Br-RT (high pre-Br-RT LDH, normal post-Br-RT LDH) had superior PFS and OS compared with those with high post-Br-RT LDH and similar PFS and OS compared with those with normal baseline LDH. In this particularly high-risk cohort, Br-RT before CAR-T demonstrates an acceptable toxicity profile with favorable clinical outcomes compared with historical controls. Comprehensive Br-RT and LDH normalization after Br-RT may be associated with superior PFS and OS.
ISSN:2473-9529

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