Anti-PD1-induced collagenous colitis in a melanoma patient

Abstract

Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first-line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 µm thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab.

Immune‐related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies

“…Although the findings in the stomach and duodenum fall within a narrow histological spectrum, ICI‐associated colitis is linked to a broad range of morphological alterations . It is of note that one‐quarter of all patients presenting with diarrhoea lacked detectable colonic histological abnormalities, and the majority of these cases showed ICI‐associated histological changes in the upper GI biopsies, an observation that reinforces the need to evaluate gastric and duodenal biopsies.…”

Diarrhoea in a Melanoma Patient

“…The KEYNOTE-001 trial, assessing the efficacy and safety of pembrolizumab, reported an incidence of 20% of diarrhoea, however only 4 cases of proven colitis out of 411 patients on pembrolizumab in the trial [1]. To date, there is one other published case of colitis with pembrolizumab, however they describe a collagenous colitis, in contrast to this example of lymphocytic colitis [2].…”

EGFR or PD-L1 decision for first line therapy in a case series of EGFR positive and PD-L1 >50%

“…Immunotherapy has different adverse effects from tyrosine kinase inhibitors and non-specific chemotherapy, however; the medical background of a patient is very important. In one of our patients ulcerative colitis was considered an issue for immunotherapy treatment, since we know that this form of therapy induces colitis [14]. There is no way to actually compare these two treatments since their mode of action is based on two different concepts.…”