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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Elsevier
2025-07-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002186 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nikhil Yegya-Raman |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ca09c51d3124ff9b5534b087dba976a |
| institution | Matheson Library |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-5ca09c51d3124ff9b5534b087dba976a2025-06-28T05:30:43ZengElsevierBlood Advances2473-95292025-07-0191332933303Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter studyNikhil Yegya-Raman0John P. Plastaras1Christopher M. Wright2Monica Chelius3Siqi Zhang4Jonathan A. Baron5Harper Hubbeling6Austin J. Sim7Timothy J. Robinson8Michael D. Jain9Brandon Imber10Beatrice Fregonese11Joachim Yahalom12Colton Ladbury13Savita Dandapani14Chelsea C. Pinnix15Jillian R. Gunther16Penny Q. Fang17Susan Y. Wu18Bouthaina S. Dabaja19Joanna C. Yang20Jessica Chew21Steve Braunstein22Sumi Sinha23Nathan M. Delinger24Susan Sun25Stephanie A. Terezakis26Gukan Sakthivel27Louis S. Constine28Amit K. Chowdhry29Patrick M. Reagan30Skyler Burke31Yolanda D. Tseng32Michael J. LaRiviere33Amit Maity34Stephen J. Schuster35Elise A. Chong36Nicholas B. Figura37Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA; Radiation Oncology Associates, Burlington, MADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PACenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Radiation Oncology, Moffitt Cancer Center, Tampa, FL; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OHDepartment of Radiation Oncology, Moffitt Cancer Center, Tampa, FL; Department of Therapeutic Radiology, Yale Cancer Center, New Haven, CTDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FLDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Radiation Oncology, City of Hope National Medical Center, Duarte, CADepartment of Radiation Oncology, City of Hope National Medical Center, Duarte, CADepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Radiation Oncology, Washington University in St. Louis, St. Louis, MODepartment of Radiation Oncology, University of California, San Francisco, CADepartment of Radiation Oncology, University of California, San Francisco, CADepartment of Radiation Oncology, University of California, San Francisco, CADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OHDepartment of Radiation Oncology, University of Minnesota, Minneapolis, MNDepartment of Radiation Oncology, University of Minnesota, Minneapolis, MNDepartment of Radiation Oncology, University of Rochester Medical Center, Rochester, NYDepartment of Radiation Oncology, University of Rochester Medical Center, Rochester, NYDepartment of Radiation Oncology, University of Rochester Medical Center, Rochester, NYDepartment of Medicine, Hematology/Oncology, Wilmot Cancer Institute, University of Rochester School of Medicine, Rochester, NYDepartment of Radiation Oncology, University of Washington/Fred Hutchinson Cancer Center, Seattle, WADepartment of Radiation Oncology, University of Washington/Fred Hutchinson Cancer Center, Seattle, WADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PADepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA; Department of Radiation Oncology, Huntsman Cancer Institute and University of Utah Health, Salt Lake City, UTHematology/Oncology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PAHematology/Oncology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Elise A. Chong, Perelman Center for Advanced Medicine, 3400 Civic Center Blvd, South Pavilion Extension, 12th Floor, Philadelphia, PA 19104;Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Correspondence: Nicholas B. Figura, Department of Radiation Oncology, H. Lee Moffitt Cancer Center, 12902 USF Magnolia Dr, Tampa, FL 33612;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.http://www.sciencedirect.com/science/article/pii/S2473952925002186 |
| spellingShingle | 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 Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study Blood Advances |
| title | Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study |
| title_full | Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study |
| title_fullStr | Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study |
| title_full_unstemmed | Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study |
| title_short | Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study |
| title_sort | bridging radiotherapy before chimeric antigen receptor t cells for b cell lymphomas an ilrog multicenter study |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002186 |
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