M. Chelius1, J. Baron1, N. Yegya-Raman2, E. Chong3, S. D. Nasta4, D. J. Landsburg4, S. Barta4, J. Svoboda4, S. Schuster4, M. J. LaRiviere2, J. P. Plastaras2, E. A. Chong4, and H. G. Hubbeling5; 1Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 3Hospital of the University of Pennsylvania, Philadelphia, PA, 4Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, 5Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Bispecific antibodies have recently received approval for relapsed refractory B-cell lymphomas (r/r BCL). Little is known about the safety of radiation (RT) delivered with bispecific therapy (BT). We sought to assess the toxicity of combination therapy with BT and RT. Materials/
Methods: We retrospectively identified patients (pts) at a single institution receiving BT and RT between 2018 and 2023. The temporal relationship of RT with respect to BT was defined as follows: “Pre-BT” RT 3 months (mo) prior to and up to the first dose of BT, “Peri-BT” 1 or more RT fractions between the first and last bispecific dose, “Post-BT” RT after the last BT dose through 3 mo post-BT. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT, and all other toxicities per CTCAEv5. Results: 19 patients underwent 20 courses of BT and received RT to 34 lesions. BT included mosunetuzumab (8), blinatumomab (7), epcoritamab (4), and glofitamab (1), with median BT treatment duration of one mo (0-6). Median follow up post RT and post BT was 2 mo (0-48) and 1 mo (0-48), respectively. Baseline characteristics were as follows: median age 61 (45-86), 25% female, 55% ECOG 0-1, histology DLBCL 65%, FL 25%, Grey zone 5%, Burkitt 5%, prior treatments 4.5 (1-12), 45% prior CAR T, 85% advanced stage, 80% extranodal, and 15% bulky disease (>10cm). Of the radiated lesions, 56% were Pre-BT (38% within 4 weeks of BT start), 21% Peri-BT, and 26% Post-BT. Sites treated included 29% spine/paraspinal, 21% abdomen/pelvis, 18% axilla, 15% head/neck, 6% skin/subcutaneous, 6% thorax, 6% CNS. 88% of lesions received RT with palliative intent. 16% of pts received comprehensive RT to all active lesions (5% bridging pre BT, 11% salvage). Median CTV was 174cc (10-4376). Median total dose was 20Gy (4-45). Among DLBCL pts, the most common regimens included 20Gy/5fx (64%), 8Gy/2fx (16%), and 30Gy/10fx (12%). Common regimens among FL pts included 4Gy/2fx (50%), 8Gy/2fx (17%), and 30Gy/10fx (17%). CRS and ICANS events were infrequent, and all low grade (4 (20%) Gr 1-2; 3 (15%) Gr 1-2, respectively). Radiation-related toxicities were similarly all low grade. Of all lesions treated, 35% were associated with Gr 1 toxicities, and 24% with Gr 2. Toxicities included fatigue (29%), dermatitis (21%), nausea (9%), GI (15%), pain (3%) and dry mouth (3%). No patients were hospitalized for bispecific related toxicity. Conclusion: RT with BT appears safe, with acceptable rates of low grade, RT-related toxicity. CRS and ICANS events were infrequent and all low grade, suggesting no obvious exacerbation by RT. The safety and efficacy of combination RT and BT warrants further study in larger cohorts.
