Pathological landscape of tumor flare reaction to epcoritamab treatment

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed “tumor pseudoprogression.” The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20⁺ large atypical lymphocytes forming residual nodules, encircled by CD4⁺ and CD8⁺ lymphocytes, with a predominance of CD8⁺ T cells over CD4⁺ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.