Objectives: Immune checkpoint inhibitors have become a standard treatment in patients with metastatic malignant melanoma. Showing significant anti-tumor effects by unleashing the immune-system, checkpoint inhibitors can also cause high-grade immune-related adverse events, with immune-related diarrhea and colitis (irColitis) being amongst the most frequent ones. While the majority of patients with irColitis respond well when treated according to standard treatment algorithms with corticosteroids +/- other immunomodulatory drugs such as infliximab, some patients do not show resolution of diarrhea and colitis. In the present study, we analyzed the frequency of therapy-refractory irColitis, the underlying cause and useful diagnostic measures.
In this retrospective, monocenter study we collected data of 370 patients with metastatic malignant melanoma. All patients had been treated with checkpoint inhibitors at the skin cancer unit of the Department of Dermatology at the University Hospital Essen from 2006-2016. Demographic and clinical data of all patients were collected. Digital patient records of all 370 patients were searched for the terms “diarrhea” and “colitis”.
We identified 41 patients with irColitis, the majority occurring during treatment with ipilimumab. Amongst these patients, 5 (12.2%) were refractory to standard immunomodulatory treatment with corticosteroids and infliximab. Therapy-refractory cases tended to show more severe inflammation in colonic biopsies performed during colonoscopy (p = 0.04). CMV-DNA in colonic biopsies and in plasma was significantly more often detectable in therapy-refractory cases (80% vs. 6.75% in non-refractory cases in biopsies, 80% vs. 0% in plasma). Presence of serum CMV IgM as well as positive immunohistochemical stainings of colon biopsies for CMV were also strongly associated with refractory colitis (40% in refractory vs. 0% in non-refractory cases), but not reliable markers in the majority of refractory patients.
This report on CMV reactivation during management of checkpoint inhibitor induced colitis emphasizes the need for repetitive diagnostic measures in treatment-refractory irColitis.
Clinical trial identification
Legal entity responsible for the study
Ethics comittee of the University Hospital Essen, University of Diusburg-Essen
All authors have declared no conflicts of interest.