International journal of radiation oncology, biology, physics · 2024
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.
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Manzar Gohar S, Wu Susan Y, Dudzinski Stephanie O, Cha Elaine E, Yoder Alison K, Corrigan Kelsey L, Nasr Lewis F, Sallard Gabrielle, Ahmed Sairah, Fayad Luis E, Chihara Dai, Nair Ranjit, Westin Jason R, Daher May, Neelapu Sattva S, Nastoupil Loretta J, Gunther Jillian R, Pinnix Chelsea C, Dabaja Bouthaina S, Strati Paolo, Fang Penny Q
Аннотация
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.
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.