Bone marrow volume irradiated and risk of cytopenias in aggressive b‐cell lymphoma patients bridged with radiation therapy for cart cell therapy

Introduction: Patients (pts) with aggressive B cell lymphomas undergoing anti-CD19-directed chimeric antigen receptor T cell therapy (CART) can benefit from bridging radiation therapy (bRT) as immune priming. Previously, by measuring the bone marrow (BM) volume irradiated in multiple myeloma pts, we established that RT does not adversely affect stem cell collection.1 Here, we examined the impact of irradiated BM distribution on the risk of acute cytopenias after bRT prior to CART. Methods: We retrospectively reviewed adults with DLBCL between 2017 and 2022 who received bRT prior to CART, which included axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel. Clinical characteristics, labs, and response were extracted. RT plans were reviewed; % BM irradiated was calculated as described previously with published estimates of skeletal BM distribution.2 Progression free survival (PFS), disease specific survival (DSS) and overall survival (OS) were modeled using the Kaplan-Meier method. Binary logistic regression and Mann-Whitney U correlated RT distribution with cytopenias (anemia, thrombocytopenia, and neutropenia per CTCAE v4.03). Results: Fifty-one pts received bRT, of which 13 (25.5%) had bulky disease (≥10 cm). Majority received bRT alone; 16 (31.4%) were additionally bridged with systemic therapy. The median bRT was 30 Gy (range: 4–48 Gy) and 26 pts (51%) pts received ≥30 Gy. Thirty-one pts (61%) received bRT comprehensively to all disease sites. The incidence of ≥Grade 3 cytopenias in timepoints following bRT are shown below. The median cumulative % of BM irradiated was 5.05% (range: 0%–50%). Nine pts (18%) received bRT encompassing ≥15% of the BM, for whom there was no increased incidence of ≥Grade 3 cytopenias overall (as well as specifically anemia, thrombocytopenia, and neutropenia) at any timepoint (all p > 0.2). Receipt of RT comprehensively to all disease sites, or bridging with both RT + systemic therapy, or delivery of ≥30 Gy bRT did not correlate with the incidence of ≥Grade 3 cytopenias at any timepoint. Regarding outcomes, 26 pts (51%) had CR at 30 days post-CART. Sixteen had PR (31.4%), and 9 pts (17.6%) had PD or SD. The OS/PFS were 84% (71–92)/78% (64–87) at 1 year, and 59% (44–71)/57% (42–70) at 2 years. Twenty-seven pts (52.9%) remain alive at last follow-up, 19 (70.4%) of whom have no evidence of disease. Conclusions: bRT is not associated with increased incidence of cytopenias, even for doses ≥30 Gy, when encompassing ≥15% of the BM, or when pts are treated comprehensively to all disease sites. While bRT can be delivered safely, we still urge careful field design to ensure minimum BM is treated to incorporate into pre-CART regimens. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, radiation therapy Conflicts of interests pertinent to the abstract R. E. Steiner Research funding from Seagen, BMS, GSK and Rafael pharmaceuticals.