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

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.

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Publication Details

Journal
Blood Advances
Published
2025-04-09
DOI
https://doi.org/10.1182/bloodadvances.2025015855
Citations
5
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
5.23

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article

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

Joanna Chensi Yang, Louis S. Constine, Austin J. Sim, Michael David Jain et al.
5 citations
Blood Advances
CAR-T cell therapy research
5.23
article

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

Joanna Chensi Yang, Louis S. Constine, Austin J. Sim, Michael David Jain, Joachim Yahalom, Bouthaina Shbib Dabaja, Chelsea C. Pinnix, Elise A. Chong, Christopher M. Wright, Gukan Sakthivel, Brandon S. Imber, Colton Ladbury, Nicholas Figura, Jillian R. Gunther, Amit Maity, Savita V. Dandapani, Yolanda D. Tseng, Monica Chelius, Beatrice Fregonese, Jonathan Baron, Amit K. Chowdhry, Michael J. LaRiviere, Harper Hubbeling, Penny Q. Fang, Stephanie A. Terezakis, Nathan Denlinger, Steve E. Braunstein, Patrick M. Reagan, Skyler Burke, Stephen J. Schuster, Susan Wu, Nikhil Yegya‐Raman, Sumi Sinha, Timothy J. Robinson, John P. Plastaras, Siqi Zhang, Susan Sun, Jessica Chew
article en
5 citations

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.

Blood AdvancesVol. 9(13)
City Of Hope National Medical Center (US), University of Minnesota (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of California, San Francisco (US), University of Washington (US), Washington University in St. Louis (US), Hospital of the University of Pennsylvania (US), University of Minnesota System (US), Huntsman Cancer Institute (US), Yale Cancer Center (US), University of Rochester Medical Center (US), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), City of Hope (US), UPMC Hillman Cancer Center (US), Colorado Permanente Medical Group (US), UFA (United States) (US), Radiation Oncology Associates (US), The Ohio State University (US), University of Rochester (US), University of Pennsylvania (US)
Bristol-Myers Squibb, AstraZeneca, Gilead Sciences, BeiGene, Seagen, MorphoSys, Genentech, Legend Biotech
Good health and well-being
Openalex Percentile: Top 4%
CAR-T cell therapy research
5.23
DOIOpen Access PDFOpenAlex
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