2693 - Safe Integration of Radiation Therapy with Bispecific Antibodies in Relapsed/Refractory B-Cell Lymphomas
Presenter(s)
J. Baron1, M. Chelius1, G. Singh1, M. Berger1, E. Chong2, C. Thomas3, J. Carter3, S. D. Nasta3, D. J. Landsburg3, S. Barta3, J. Svoboda3, S. Schuster3, N. Yegya-Raman4, M. J. LaRiviere1, J. P. Plastaras1, E. A. Chong3, and H. G. Hubbeling1; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Hospital of the University of Pennsylvania, Philadelphia, PA, 3Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, 4Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): T-cell–engaging bispecific antibodies (BsAbs) are increasingly used to treat relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL). In this setting, radiation therapy (RT) can be employed for palliation or cytoreduction; however, data evaluating the safety of RT delivered in close temporal proximity to BsAbs are limited and the potential for severe hematologic toxicity with combined therapy is unknown. We evaluated the toxicity of RT administered before, during, or after BsAb therapy with particular attention to post-RT cytopenias.
Materials/Methods: We retrospectively identified patients with B-NHL who received RT =3 months before, during, or =3 months after BsAb therapy at a single institution from 2018–2024. Timing was categorized as pre-BsAb, peri-BsAb, or post-BsAb. Toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), were graded per ASTCT criteria; other adverse events were graded per CTCAE v5.0. Early lymphopenia (first post-RT lab within 30 days) was evaluated. In-field responses after RT were assessed per Lugano criteria.
Results: Twenty-nine patients (median age 60) underwent 31 BsAb courses and received RT to 52 sites (50% pre-BsAb, 13% peri-BsAb, 38% post-BsAb). Patients had received a median of 4 prior systemic therapy lines (range, 1–12). Common histologies included DLBCL (52%), follicular lymphoma (26%), and transformed FL (16%); most RT was palliative (88%). All RT-related toxicities were grade 1–2, with no RT-related hospitalizations. CRS occurred in 7 BsAb courses and ICANS in 4, without an apparent relationship to RT timing or dose. Among 35 RT courses with available labs =30 days post-RT, early lymphopenia (pre/peri/post: 94%/60%/79%) and high-grade lymphopenia (75%/40%/71%) were common; however, time between RT and BsAb exposure (days) was not associated with early lymphopenia (OR 0.81 per 10-day increase; p=0.21) or high-grade lymphopenia (OR 1.03; p=0.74). Among 44 evaluable lesions with post-RT imaging, the in-field overall response rate (ORR) was 84% (CR 45%, PR 39%), including ORR 82% pre-BsAb, 100% peri-BsAb (3 CR, 2 PR), and 86% post-BsAb.
Conclusion: RT administered before, during, or after BsAb therapy was well tolerated, without apparent additive toxicity, and achieved high rates of in-field response. These early findings support the safe integration of RT with BsAbs in R/R B-NHL.