202 - CNS Bridging Radiotherapy prior to CAR T-Cell Therapy for B-Cell Lymphomas
Presenter(s)
P. Wang1, A. Wen2, H. Gilbertson2, C. Hao1, I. Zovigian3, L. E. Budde2, M. Mei4, J. Baird4, G. Shouse4, N. Khan2, A. Herrera4, S. Thiruvengadam2, O. Okunowo2, P. Frankel5, J. Y. C. Wong1, C. J. Ladbury1, and S. V. Dandapani1; 1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2City of Hope Cancer Center, Duarte, CA, 3City of Hope, Duarte, CA, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, 5Department of Information Sciences, City of Hope National Medical Center, Duarte, CA
Purpose/Objective(s): The role of bridging radiation therapy (bRT) before chimeric antigen receptor T-cell therapy (CAR T) in patients with central nervous system (CNS) involvement from relapsed/refractory (r/r) B-cell lymphomas (LBCL) remains undefined. Whole brain radiation therapy (WBRT) has been the standard treatment for primary and secondary CNS lymphomas (CNSL). With the advent of CAR T, the role of WBRT is being reexamined, given its neurocognitive risks and CNS penetration of CAR T. We hypothesize that partial brain radiation (PBRT) as bRT prior to CAR T has promising outcomes in selected patients.
Materials/Methods: We retrospectively reviewed patients with r/r LBCL treated with CNS-bRT followed by CAR T therapy at our institution. Patients with neuroaxis disease involving the brain, spinal cord, or leptomeninges were included. CNS responses were assessed post-bRT and post-CAR T using International PCNSL Collaborative Group (IPCG) guidelines. Subgroup analysis describing outcomes in WBRT and PBRT patients was performed. Efficacy outcomes, neurotoxicity and overall survival (OS) were evaluated. OS was calculated using Kaplan-Meier curves defined from the end of bRT.
Results: Between June 2019 and January 2025, 26 patients received CNS-bRT with a median follow up of 7.0 (range, 1.5-46.6) months. The median age at diagnosis was 66 (range, 39-81) years and median Karnofsky Performance Status (KPS) was 80 (range, 40-90). All patients had secondary CNSL. Histologies included DLBCL (n=22) and mantle cell lymphoma (n=4). All patients received bRT to a median total dose of 25Gy (range, 4.0-37.5) in 8 fractions (range, 1-15). bRT targets were whole brain (n=8), involved site (partial) brain (n=6), orbits (n=3), and involved spine (n=9). For the subgroup analysis of patients with brain parenchymal disease (n=14), median follow up was 11 months (range, 1.5-39.3) and median total dose was 25.5Gy (range, 4.0-37.5) in 5 fractions (range, 2-17). PBRT patients had limited disease with median gross tumor volume (GTV) of 19.38 cc (range, 4.42-51.02). For PBRT patients, CNS-bRT achieved a 43.0% (95% CI, 22.2%-63.8%) average decreases in lesion size prior to CAR T. At last follow-up, CNS disease progression was observed in 3/8 (37.5%) patients who received WBRT, whereas no CNS disease progression has been observed in PBRT patients. 5/14 (35.7%) patients with brain parenchymal disease received memantine. No = grade 2 acute or late bRT neurotoxicity was observed in all 14 patients. Median OS in patients selected for PBRT was not reached (median follow-up for PBRT:19.5 months, range 3.8-39.3 months). Median OS was 11.9 months (95%CI, 6.01-NR) in the WBRT cohort (median follow-up for WBRT: 9.5 months, range 1.5-18.9 months).
Conclusion: CNS-bRT, whether delivered as WBRT or PBRT, provides effective lesion control in CNSL. PBRT may be particularly effective in settings of limited brain parenchymal disease. Further investigation is needed to elucidate the optimal approach for treatment of CNS lymphomas.