Cytomegalovirus Infections in Patients Treated With Immune Checkpoint Inhibitors for Solid Malignancies

Abstract

Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV infection/disease in patients treated with ICIs for solid malignancies. We present the currently available data on the pathogenesis, clinical characteristics, endoscopic findings, and histologic features and highlight the potential differences among cases complicating R/R irAEs versus those occurring in patients who are immunosuppression naive. Finally, we discuss the currently available data regarding potential useful diagnostic tools as well as the management of these patients.

Keywords: cytomegalovirus; immune-checkpoint inhibitors; immune-related adverse events; immune-related colitis; review.

Figure 1.

Histological examination images of our patient. (A) Fibropurulent material and gastric mucosa with acute inflammation suggestive of phlegmonous gastritis, initial biopsy (hematoxylin and eosin stain, ×100). (B) Immunohistochemistry (IHC) for cytomegalovirus (CMV) was performed retrospectively at the initial biopsy specimen (anti-CMV CCH2 + DDG9, Dako Omnis; Agilent). A CMV⁺ nuclei was identified (IHC, ×200). (C) Several positive nuclei for CMV on second biopsy, which was performed 3 months later (IHC, ×200). (D) Positive nuclei for CMV in third biopsy, performed 4 months later (IHC, ×200); cytoplasmic staining was not evaluated. (E and F) A fourth esophagogastroduodenoscopy was performed 2 months later, and IHC on multiple biopsy specimens revealed the presence of multiple CMV⁺ cells in one biopsy specimen (E) and absence in another (F).