[666] Ipilimumab Induced Enterocolitis: A Clinico-Pathologic Study

B Kenney, C Loeser, M Sznol, H Kluger, D Jain, K Mitchell. Yale University School of Medicine, New Haven; Yale University School of Medicince, New Haven

Background: Ipilimumab (IP), a monoclonal antibody to cytotoxic T-cell associated antigen 4 is under investigation for treatment of metastatic melanoma (MM) and other malignancies. Enterocolitis (EC) observed in 25-35% of patients responds to steroid and anti-TNF therapy and is believed to be immune mediated. Limited descriptions of gastrointestinal (GI) involvement exist. The study goal was to perform a histopathologic analysis of IP induced EC and correlate with clinical features.
Design: All patients with MM treated at our institution with IP 10mg/kg q3week x 4 then q3months with persistent diarrhea (> grade 2) and had endoscopy were included. All GI biopsies were retrospectively reviewed for histologic changes. Correlation with clinical presentation and response to treatment was performed.
Results: 20 of 54 patients treated with IP (37%) developed diarrhea. 14 patients had endoscopy, 11 of which were biopsied. A total of 75 biopsies (large bowel-53, ileum-3, duodenum-8, stomach-6, esophagus-5) were reviewed. Proctocolitis was most frequent (34) {mild (8), moderate (25) or severe (1)}; most consistently seen as increased lamina propria lymphoplasmacytic inflammation, cryptitis, crypt abscesses, mucin depletion, crypt atrophy and erosions/ulcers. Crypt branching, Paneth cell metaplasia and basal plasmacytosis were infrequent. General patterns on initial biopsy were autoimmune (AI) enteropathy (4), infectious EC (4) and non-specific/ overlapping features (3). 1 patient with deep ulcers and intramural abscesses later had colonic perforation with tapering of steroids. 2 patients had enteritis with no colitis (villous blunting of duodenal/ileal mucosa, without significant intraepithelial lymphocytes). Gastritis was always accompanied by duodenitis (6). Esophagitis was not seen. Follow up biopsies showed histologic progression in 4, improvement in 2, and no change in 3. 18 of the 20 with diarrhea were evaluable for tumor response; 4 (22%) had clinical objective tumor responses (ongoing), 5 had mixed/ transient tumor regression; there was no correlation with severity of diarrhea or colitis.
Conclusions: The spectrum of GI inflammatory changes induced by IP therapy is wide and may mimic self-limited colitis, inflammatory and AI enteritis, however, subtle differences exist. While mechanisms of GI toxicity are unclear, awareness of the spectrum of changes is necessary to avoid diagnostic errors.
Category: Gastrointestinal

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 74, Tuesday Afternoon

 

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