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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. 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 CTCAE version 5. Nineteen 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 (> 10 cm). 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. Eighty-eight percent 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 174 cc (10-4376). Median total dose was 20 Gy (4-45). Among DLBCL pts, the most common regimens included 20 Gy/5 fx (64%), 8 Gy/2 fx (16%), and 30 Gy/10 fx (12%). Common regimens among FL pts included 4 Gy/2 fx (50%), 8 Gy/2 fx (17%), and 30 Gy/10 fx (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. 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. [ABSTRACT FROM AUTHOR]