Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis

Autor: Elisabeth Livingstone, Saskia Herz, Melanie Fiedler, Dirk Schadendorf, Isabelle Rooms, Kurt Werner Schmid, Henning Reis, Ulf Dittmer, Bastian Schilling, Cindy Franklin, Laura Milsch, Lisa Zimmer
Rok vydání: 2017
Předmět:
Male
Cancer Research
Skin Neoplasms
Time Factors
Immune checkpoint inhibitors
Medizin
Cytomegalovirus
Antibodies
Viral
Gastroenterology
Hospitals
University
Antineoplastic Agents
Immunological
0302 clinical medicine
Risk Factors
Germany
Melanoma
Aged
80 and over
Hematology
Middle Aged
Colitis
Diarrhea
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Cytomegalovirus Infections
Host-Pathogen Interactions
Female
030211 gastroenterology & hepatology
medicine.symptom
Immunosuppressive Agents
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Congenital cytomegalovirus infection
Ipilimumab
Opportunistic Infections
Antiviral Agents
Immunocompromised Host
Young Adult
03 medical and health sciences
Refractory
Predictive Value of Tests
Internal medicine
medicine
Humans
In patient
Adverse effect
Ganciclovir
Aged
business.industry
medicine.disease
Infliximab
DNA
Viral
Immunology
Cancer research
Virus Activation
business
Zdroj: Annals of Oncology. 28:v421-v422
ISSN: 0923-7534
DOI: 10.1093/annonc/mdx376.055
Popis: 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.
Databáze: OpenAIRE
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