Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma

Abstract

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.

Nivolumab-Induced Colitis in a Patient With Esophageal Adenocarcinoma: A Case Report

“…IMC is one of the reported adverse events of these drugs. Some of the symptoms of immune checkpoint inhibitor-associated colitis include diarrhea, abdominal pain, hematochezia, fever, and vomiting [ 1 , 3 , 5 ]. Among these symptoms, diarrhea is the most common but is of variable severity and onset [ 6 ].…”

“…National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) has defined the grades of diarrhea and colitis during treatment with immune checkpoint inhibitors. The majority of these cases of diarrhea are mild [ 1 , 6 ]. Specifically, most are categorized as grade 1 (fewer than four stools per day) or grade 2 (four to six stools per day), while grades 3-4 (more than seven stools per day and life-threatening diarrhea, respectively) rarely occur (1%-2% of the patients in a clinical trial with anti-programmed cell death protein 1 {PD-1} therapy) [ 7 , 8 ].…”

“…The exact pathophysiologic mechanism of immune checkpoint inhibitor-associated colitis is not known. However, some suggested mechanisms include the hyperproliferation and hyperactivation of T cells and lymphocyte infiltration [ 1 ].…”

“…Drug-induced colitis was originally described as a side-effect of nonsteroid anti-inflammatory drugs and is also commonly associated with antibiotic usage. More recently, as immune checkpoint inhibitors have been developed and used in the treatment of several malignancies, immune-mediated colitis (IMC) is reported as a potential drug-induced side effect [ 1 ]. These drugs activate certain elements of the immune system to improve antitumor immunity, enhancing the activity of T cells against cancer cells and thus making them a novel treatment option for various types of cancer, such as melanoma, lung cancer, bladder cancer, renal cell carcinoma, and esophageal cancer [ 2 , 3 ].…”

Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer

“…GIT adverse effects are commonly brief and minor, appearing after around six weeks after starting treatment [8]. However, when nivolumab is combined with ipilimumab, a high grade of diarrhea is recorded in more than 9% of patients [100]. Patients that have ileal rupture are relatively uncommon following immunotherapy for terminal ileitis except colitis, especially when used in tandem [101].…”