First Reported Case of Immune-Mediated Colitis due to Epcoritamab

Bispecific antibodies (BsAbs) are engineered immunotherapy agents. They function by simultaneously binding CD3 on T-cells and tumor-associated antigens. This binding allows the formation of an artificial immune synapse that redirects cytotoxic T-cell activity towards malignant cells. In recent years BsAbs have become increasingly important in the management of hematological malignancies. An example of this is epcoritamab, a CD3xCD20 BsAb approved by the FDA for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) and relapsed/refractory follicular lymphoma (R/R FL). Nevertheless, use of these BsAbs is not without peculiar risks as they carry a unique toxicity profile. The most well-known toxicities include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are both driven by overactivation of the immune system. Immune-mediated gastrointestinal (GI) toxicities, including chronic diarrhea and colitis, have also been reported with the use of CD3xCD20 BsAb glofitamab, but not epcoritamab. Here, we report the first case of persistent chronic diarrhea due to immune-mediated colitis following use of epcoritamab in a patient with R/R FL.

We report a 70-year-old man with relapsed/refractory follicular lymphoma, who was treated with epcoritamab, and developed persistent diarrhea, which continued after discontinuation of epcoritamab, and resolved with the administration of high dose corticosteroids. This case highlights a potentially new immune-mediated gastrointestinal toxicity associated with epcoritamab. Oncologists, gastroenterologists, and pharmacists should rule out immune-mediated colitis in patients treated with epcoritamab who develop diarrhea.

In conclusion, this case describes a rare presentation of persistent immune-mediated colitis associated with epcoritamab therapy in a patient with relapsed/refractory follicular lymphoma. Although BsAbs are primarily associated with CRS and ICANS, this report demonstrates that prolonged GI immune-related adverse events may also occur, even after treatment discontinuation. Chronic diarrhea is an emerging toxicity of BsAbs, making immune-mediated GI toxicities an increasing diagnostic challenge. The patient's negative infectious workup, biopsy-proven colitis, and clinical response to corticosteroids strongly support an immune-mediated mechanism of injury. As the use of CD3xCD20 BsAb continues to expand, oncologists, gastroenterologists, and pharmacists should maintain a high index of suspicion for delayed or persistent GI toxicities in patients presenting with chronic diarrhea. Early recognition, exclusion of infectious etiologies, and timely colonoscopy evaluation are essential to establishing the diagnosis and guiding treatment.