Main Session
Sep
28
PQA 04 - Breast Cancer, Patient Reported Outcomes/QoL/Survivorship, Functional Radiation Medicine, Hematologic Malignancies, Palliative Care, and International/Global Oncology
2779 - Comprehensive Bridging Radiation to All Sites of FDG-Avid Disease Prior to CAR T-Cell Infusion in Patients with Large B-Cell Lymphoma: A Prospective Trial
Presenter(s)
Colton Ladbury, MD - City of Hope National Medical Center, Duarte, CA
C. J. Ladbury1, H. Gilbertson2, C. Hao3, A. Wen2, S. Yoon2, J. Y. C. Wong2, J. Li4, K. Feghali5, S. M. Shirvani5, A. Kallam6, J. Baird6, B. Sworder6, G. Shouse6, M. Mei6, L. E. Budde7, and S. V. Dandapani2; 1Department of Radiation Oncology, Orange County Lennar Foundation Cancer Hospital, Irvine, CA, 2Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 3Johns Hopkins Medical School, Baltimore, MD, 4Division of Biostatistics, City of Hope National Medical Center, Duarte, CA, 5RefleXion Medical, Inc., Hayward, CA, 6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, 7Department of Hematology and Hematopoietic Cell Transplantation, Duarte, CA
Purpose/Objective(s):
Patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) often receive bridging therapy between leukapheresis and chimeric antigen receptor (CAR) T-cell infusion. Retrospective data suggest that cytoreduction associated with bridging radiation therapy (BRT) can yield favorable response rates and disease control, particularly if all sites of disease can be included. This study sought to prospectively evaluate a comprehensive BRT strategy in patients with limited LBCL planned for CAR T-cell therapy.Materials/Methods:
Patients with LBCL with 6 or fewer sites of disease (defined based on Ann Arbor nodal regions or extranodal masses with clear planes of separation on CT) who were planned for commercial CAR T-cell therapy were eligible. CNS disease was excluded. Planned sample size was 9 patients. BRT was to occur between leukapheresis and CAR T-cell infusion. High-risk sites (defined as SUVmax>10 or >7.5 cm) were treated to a total dose of 30 Gy in 10 fractions, while non-high-risk sites received 24 Gy. An elective nodal dose of 20 Gy was allowed at the treating radiation oncologist’s discretion.Results:
A total of 9 patients were accrued between July 2023 and April 2025. The median age was 60.4 years (range, 31.9–79.1), and 55.6% were male. Histologic subtypes included DLBCL (n=5), tFL (n=3), and PMBCL (n=1). Nineteen sites were irradiated: 1 site in 5 patients, 2 sites in 1 patient, 3 sites in 2 patients, and 6 sites in 1 patient. The most common location was the cervical neck (n=4), and 8 sites were extranodal. All but one site was categorized as high-risk. All patients underwent lymphodepletion and CAR T-cell infusion (7 axi-cel; 2 liso-cel). Cumulative Grade =2 radiation-related toxicity occurred in 66.7% of patients and included cytopenias, fatigue, mucositis, diarrhea, neck pain, joint stiffness, dermatitis, esophagitis, and palpitations Grade 3 toxicity occurred in 11.1% of patients (one case of pneumonitis that resolved 1 month after radiation was complete). The ORR following RT was 100% (22.2% CR; 77.8% PR). Best ORR was 100% (89% CR; 11% PR). Median follow-up was 17.0 months (7.4–28.5). One and two-year OS and PFS were both 87.5% (95% CI, 67.3–100%). The single patient who progressed had isolated axillary disease, developed out-of-field progression on post-RT PET prior to CAR T-cell therapy and initially achieved a partial response after CAR T-cell infusion. She later experienced widespread progression, including in-field, approximately 6 months afterward, and succumbed to disease progression 1 month later.Conclusion:
For patients with limited sites of disease prior to CAR T-cell therapy, comprehensive bridging radiation is well-tolerated. Disease response and survival outcomes appear favorable in a limited sample size. Larger prospective studies are warranted to define the role of cytoreductive radiation in patients with limited disease planned to undergo cellular therapy. Correlative studies, including flow cytometry, PET radiomics, and ctDNA, are planned.