Immunotherapy targeting the PD-1/PD-L1 and CTLA-4 pathways is being used with increasing frequency to treat various advanced cancers, including melanoma. This therapy has been associated with immune-related adverse events that may potentially require treatment with immunosuppressive agents. Little is known about the development of opportunistic infections amongst patients treated with these immunotherapeutic agents; however, at least in animal models, these pathways seem to be of importance in the defense against certain infections. Our aim is to determine the scope and risk factors for opportunistic infections among patients receiving CTLA-4 and/or PD-1/PD-L1 inhibitors for treatment of metastatic melanoma.
Retrospective review of patients with metastatic melanoma that received treatment with CTLA-4, PD-1 and/or PD-L1 inhibitors at MSKCC between January 2011 and November 2014.
742 patients were treated with CTLA-4 and/or PD-1/PD-L1 inhibitors for metastatic melanoma at MSKCC during the study period. These patients received 908 courses of immunotherapy, including 673 course of ipilumimab (CTLA-4 blocker), 65 of nivolumab (PD-1 blocker), 82 of pembrolizumab (PD-1 blocker), 10 of MEDI4736 (PD-L1 blocker), and 78 of ipilumimab+nivolumab. The mean age was 65 and 469 (63%) were men. 315 patients (42%) received corticosteroids after the immunotherapy, of whom 56 (7.5%) were also treated with a TNF-alpha inhibitor (infliximab). 3 patients were treated with infliximab alone. 17 patients (2%) developed opportunistic infections, including Aspergillus invasive pulmonary infection, Pneumocystis pneumonia, Strongyloides hyperinfection, candidemia, esophageal candidiasis, and VZV, HSV and CMV reactivation. Development of an opportunistic infection was strongly associated with use of corticosteroids and/or infliximab (OR 4.48, 95% CI 1.44 to 13.85, p=0.004).
Opportunistic infections in patients treated with CTLA-4 and/or PD-1/PD-L1 inhibitors are rare. The main risk factor associated with development of these infections is use of corticosteroids and/or TNF-alpha inhibitors for treatment of complications of immunotherapy.
M. Del Castillo Garcia,
See more of: Poster Abstract Session