Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: An ILROG multicenter study Journal Article
| Authors: | Yegya-Raman, N.; Plastaras, J. P.; Wright, C. M.; Chelius, M.; Zhang, S.; Baron, J. A.; Hubbeling, H.; Sim, A. J.; Robinson, T. J.; Jain, M. D.; Imber, B.; Fregonese, B.; Yahalom, J.; Ladbury, C.; Dandapani, S.; Pinnix, C. C.; Gunther, J. R.; Fang, P. Q.; Wu, S. Y.; Dabaja, B. S.; Yang, J. C.; Chew, J.; Braunstein, S.; Sinha, S.; Delinger, N. M.; Sun, S.; Terezakis, S. A.; Sakthivel, G.; Constine, L. S.; Chowdhry, A. K.; Reagan, P. M.; Burke, S.; Tseng, Y. D.; LaRiviere, M. J.; Maity, A.; Schuster, S. J.; Chong, E. A.; Figura, N. B. |
| Article Title: | 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 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. © 2025 American Society of Hematology. |
| Keywords: | adult; aged; treatment failure; major clinical study; overall survival; cancer radiotherapy; flow cytometry; neurotoxicity; nuclear magnetic resonance imaging; outcome assessment; progression free survival; retrospective study; b cell lymphoma; gene rearrangement; multicenter study; lactate dehydrogenase; leukapheresis; clinical outcome; cytokine release syndrome; maximum standardized uptake value; disease burden; human; male; female; article; positron emission tomography-computed tomography; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; brexucabtagene autoleucel; immune effector cell-associated neurotoxicity syndrome; bridging therapy |
| Journal Title: | Blood Advances |
| Volume: | 9 |
| Issue: | 13 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-07-08 |
| Start Page: | 3293 |
| End Page: | 3303 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2025015855 |
| PUBMED: | 40203192 |
| PROVIDER: | scopus |
| PMCID: | PMC12268022 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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