Highlights
- •Checkpoint inhibitors can cause immune-related colitis (irColitis).
- •IrColitis can be refractory to immunosuppressive and immunomodulatory therapies.
- •Refractory irColitis is often caused by reactivation of cytomegalovirus (CMV).
- •CMV colitis can resolve after the application of ganciclovir.
- •Different repetitive diagnostic measures are needed to detect CMV colitis.
Abstract
Objectives
Immune checkpoint inhibitors can cause severe immune-related adverse events, with
immune-related diarrhea and colitis (irColitis) being among the most frequent ones.
While the majority of patients with irColitis respond well to corticosteroid treatment ± other
immunomodulatory drugs such as infliximab, some patients do not show resolution of
their symptoms. In the present study, we analysed the frequency of therapy-refractory
irColitis, the underlying cause, and useful diagnostic approaches.
Methods
Between 2006 and 2016, 370 patients with metastatic malignant melanoma were treated
with checkpoint inhibitors at the Department of Dermatology at the University Hospital
Essen. All patients were identified for whom diarrhea and/or colitis was documented
in the digital patient records. Patients who did not respond to standard immunosuppressive
therapy within 2 weeks were classified as refractory. Demographic and clinical data
of all patients were collected.
Results
We identified 41 patients with irColitis, the majority occurring during treatment
with ipilimumab. Amongst these, 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 (p = 0.04). In all therapy-refractory
cases cytomegalovirus (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma
was significantly more often detectable in therapy-refractory cases (in colonic biopsies
p = 0.005, in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical
stainings of colon biopsies for CMV were also associated with refractory colitis (p=0.021;
p = 0.053).
Conclusions
This report on CMV reactivation during management of checkpoint inhibitor-induced
colitis emphasises the need for repetitive diagnostic measures in treatment-refractory
irColitis.
Keywords
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Article info
Publication history
Published online: October 19, 2017
Accepted:
September 12,
2017
Received:
July 24,
2017
Footnotes
☆This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
