Late-Onset Inflammatory Bowel Disease-Like Syndrome after Ipilimumab Therapy: A Case Report

Abstract

Background: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis. Case Presentation: We report the case of a 71-year-old male patient diagnosed with BRAF wild-type metastatic melanoma treated with three cycles of ipilimumab, after which he developed grade 3 enteritis. The patient improved on treatment with steroids, and ipilimumab was permanently discontinued at this point. Three years later, the patient’s diarrhea returned and colonoscopy revealed active chronic colitis with ulceration resembling inflammatory bowel disease. He was started on Asacol (mesalamine). The patient did not report extraintestinal symptoms typically associated with inflammatory bowel disease, nor did he have a personal or family history of bowel disorders. Moreover, his presentation was not typical of inflammatory bowel disease in the elderly. Conclusion: Our findings suggest a link between ipilimumab-induced grade 3 enteritis and late-onset inflammatory bowel disease-like syndrome. To our knowledge, the case is the first in the literature to report late-onset inflammatory bowel disease-like syndrome years after discontinuation of ipilimumab treatment.

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…This adverse condition usually presents as a triad of diarrhea, abdominal pain, and vomiting (227). Enterocolitis is particularly frequent and severe following CTLA-4 inhibition, and appears to resemble, and even cause inflammatory bowel diseases (228,229). In the above-mentioned report utilizing anti-CTLA-4 antibodies, Faecalibacterium genus and other Firmicutes not only correlated with a good treatment outcome, but also with the frequency and severity of enterocolitis (223).…”

Immunotherapy of solid tumors: how safely treat the patients

“…In the majority of patients the rectum or/and the left colon are involved therefore the flexible sigmoidoscopy is sufficient for diagnosis. However some patients need colonoscopy [22][23][24]. The endoscopic lesions include erythrema, luminal bleeding, erosions and ulcerations [22][23][24].…”

“…However some patients need colonoscopy [22][23][24]. The endoscopic lesions include erythrema, luminal bleeding, erosions and ulcerations [22][23][24]. The presence of these changes but also a normal appearance of the mucosa are usually not sufficient.…”

Anti-Inflammatory Biologics and Anti-Tumoral Immune Therapies-Associated Colitis: A Focused Review of Literature

“…Immunological studies on the biopsy material from patients with ipilimumab-associated colitis revealed abundance of plasma cells and CD4+ T cells in the lamina propria by immunohistochemistry as well as increased expression of interferon-γ and IL17A mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) [ 52 ]. Rare cases of late-onset IBD-like syndrome developing 3 years after ipilimumab therapy have been reported [ 56 ].…”