Characterization of Lymphopenia and Correlating the Risk of Cytopenias With Dose and Bone Marrow Volume Irradiated in Aggressive B Cell Lymphoma Patients Bridged With Radiation Therapy for Chimeric Antigen Receptor-T Cell Therapy

Purpose: The impact of bridging radiation therapy (bRT) for chimeric antigen receptor (CAR) T-cell therapy on absolute lymphocyte count (ALC) kinetics and treatment outcome is unknown. Methods and Materials: We retrospectively reviewed adults with relapsed/refractory aggressive large B cell lymphoma who received bRT before CD-19 CAR-T between November 2017 and April 2023. The change in ALC (ALC 0 RT) was computed by subtracting ALC pre- and post-bRT. Percent bone marrow (%BM) irradiated was calculated by estimating skeletal BM distribution. Progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were modeled via Kaplan- Meier. Results: Fifty-one patients received bRT, of which 13 (25.5%) had bulky disease (>= 7.5 cm). The median bRT dose was 30 Gy (range, 4-48 Gy); 26 patients (51%) received >= 30 Gy. Thirty-one patients (61%) received bRT comprehensively to all disease sites. The median cumulative %BM irradiated was 5.05% (range, 0-50%). At a median follow-up of 10.3 months (95% CI, 7.716.4), the 1-year OS, PFS, and DSS rates were 80% (95% CI, 66-99), 78% (64-87), and 82% (68-90), respectively. The incidence of grade >= 3 lymphopenia was 33% pre-RT and 68% post-RT, but recovered to 43% at the conditioning chemotherapy time- point. There was no correlation between post-RT grade >= 3 lymphopenia and the receipt of comprehensive bRT, combined modality bridging, >= 30 Gy bRT, or bRT to >= 15% of BM (all P> .2). Among patients with grade 0-2 lymphopenia pre-RT, increased conversion to grade >= 3 lymphopenia post-RT correlated with comprehensive or >= 30 Gy bRT, but these factors did not impair ALC recovery at conditioning chemotherapy. There was no association between ALC 0 RT or post-RT ALC with 30 or 90 day response (P> .25), DSS, PFS, or OS (P> .3). Conclusions: Lymphocyte change during bRT is not associated with CAR-T outcomes. Persistent cytopenia risk after bRT is not associated with bRT to >= 30 Gy, >= 15% of BM, or comprehensive coverage. Although bRT can be delivered safely, we urge careful treatment planning when incorporating into pre-CAR-T regimens. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.