Enterocolitis associated with glofitamab-First report and clinicopathological findings in three cases

Abstract

Glofitamab is a CD3-CD20 bispecific antibody used to treat B-cell non-Hodgkin lymphoma. We describe three cases of enterocolitis occurring with glofitamab at a single institution. Similarities between cases include onset post cycle 4-5, moderately elevated faecal calprotectin, abnormal bowel avidity on positron emission tomography scan (2/3), absence of CD20-positive B cells on gut histology and steroid responsiveness. There was variability in the area of gastrointestinal inflammation, severity of symptoms, histological findings and impact on subsequent therapy. The mechanism for this phenomenon is unknown. Possible explanations include B-regulatory cell depletion and T-cell recruitment to the gastrointestinal tract because of CD20 antigen density. Clinicians should consider this toxicity in glofitamab-treated patients presenting with sustained diarrhoea or abdominal pain when infectious colitis has been comprehensively excluded.

Keywords: T cells; drug antibodies; drugs; immune; lymphoid malignancies; lymphomas.

FIGURE 1

Case 1 (A–G)—Endoscopic appearances of sigmoid colon pre (A) and post (B) steroid therapy. Colonic biopsies demonstrate mild active colitis (C) with Crohn's‐like morphology, including scattered non‐necrotizing, tight, sarcoidal granulomas (D). There is a conspicuous lack of B cells on CD20 IHC (E) in comparison with CD3 IHC (F). PET scan shows diffuse colonic avidity (G). Case 2 (H–K)—Normal endoscopic appearance of colon (H). Colonic biopsies show only mild non‐specific inflammation (I), again with notable absence of B cells on CD20 IHC (J). PET scan shows diffuse colonic avidity (K). IHC, immunohistochemistry; PET, positron emission tomography.