The present study investigated outcomes of
infliximab (IFX) treatment among 8 Japanese patients with various types of
cancer (4 with
malignant melanoma, 3 with
lung cancer and 1 with
renal cancer) who developed severe
steroid-resistant immune-related adverse events (irAEs) in association with
immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3
diarrhea/
colitis in 7 patients and
disseminated intravascular coagulation and
myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic
steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and
antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD)
infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic
steroid administration over a long period presumably predisposed the patients to opportunistic enteric
infections. Accordingly, early initiation of IFX treatment in conjunction with systemic
steroid therapy should be considered for severe
diarrhea/
colitis and other irAEs. However, the possibility for CMV and CD
infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.