Safe Integration of Radiation Therapy With Bispecific Antibodies in Relapsed/Refractory B-cell Lymphomas

T-cell-engaging bispecific antibodies (BsAbs) are effective for relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). Radiation therapy (RT) is increasingly used for palliation or bridging/cytoreduction in patients receiving BsAbs, but data on the safety of RT delivered in close temporal proximity to BsAbs are limited. We report the largest series to date evaluating RT and BsAbs in B-NHL.

We retrospectively identified patients with B-NHL who received RT ≤ 3 months before, during, or ≤ 3 months after BsAb at a single institution between 2018 and 2024. Timing was categorized as pre-, peri-, or post-BsAb. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria; other toxicities per CTCAE v5.0. In-field responses were assessed per Lugano criteria.

Twenty-nine patients underwent 31 BsAb courses and received RT to 52 sites (50% pre-, 13% peri-, 37% post-BsAb). Common histologies included DLBCL (52%), follicular lymphoma (FL) (26%), and transformed FL (16%). All RT-related toxicities were grade 1 to 2, with no RT-related hospitalizations. CRS occurred in 7 BsAb courses and ICANS in 4, with no apparent relationship to RT timing or dose. Early post-RT lymphopenia was common across groups, but its frequency and severity did not differ by RT timing. Among 44 evaluable lesions, the in-field overall response rate was 84% (CR 45%, PR 39%).

RT before, during, or after BsAb was well tolerated, without apparent additive toxicity, and achieved high in-field response rates, supporting the safe integration of RT with BsAbs for R/R B-NHL.