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 Δ 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, 7.7-16.4), 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 timepoint. 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 Δ 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.