Cytokine release syndrome-compatible fever after initiation of local radiotherapy during late-phase epcoritamab therapy in relapsed/refractory diffuse large B-cell lymphoma: a case report

Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has demonstrated promising activity in relapsed or refractory diffuse large B‑cell lymphoma. Cytokine release syndrome (CRS) is a key adverse event associated with T‑cell–engaging therapies; however, it typically occurs early after treatment initiation and is generally manageable with step‑up dosing and premedication. Evidence regarding the safety of delivering radiotherapy during late-phase epcoritamab therapy remains limited. A 58-year-old man with diffuse large B-cell lymphoma received epcoritamab. On cycle 8 day 8, local radiotherapy (40 Gy in 20 fractions) was initiated for a residual abdominal lymph node lesion. Approximately 12 h after the second radiotherapy fraction, he developed fever (38 °C) and fatigue without hypotension or hypoxia and without neutropenia, consistent with a CRS-compatible febrile episode (grade 1 by the American Society for Transplantation and Cellular Therapy criteria). Blood cultures were obtained and empiric cefepime with acetaminophen was initiated, resulting in transient defervescence; however, fever recurred approximately 12 h after the third radiotherapy fraction. Blood cultures, (1,3)-β-D-glucan, and galactomannan assays were negative. Given the reproducible temporal association with radiotherapy, a CRS-compatible event was considered, and tocilizumab (8 mg/kg) was administered in line with standard CRS management guidance, with defervescence within 1 h. He remained afebrile thereafter and completed radiotherapy without recurrence. CRS-compatible fever is uncommon after multiple cycles of epcoritamab. This case suggests a temporal association between radiotherapy and a CRS-compatible febrile episode during late-phase therapy and supports the possibility that radiotherapy acted as an inflammatory trigger. When radiotherapy is delivered during bispecific antibody therapy, fever should prompt concurrent evaluation for infection while keeping CRS in the differential diagnosis, and standard CRS management should be applied promptly when clinically indicated.