ABSTRACT
Introduction: Immune checkpoint inhibition has emerged as an important new approach to the treatment of cancer. Agents targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1), and PD-1 ligand (PD-L1) have shown remarkable promise as anti-neoplastic drugs, but they are also associated with unique set of toxicities termed immune-related adverse events (IRAEs) that differ from toxicities observed with conventional cytotoxic chemotherapy.
Areas covered: A burgeoning body of literature suggests that patients who are treated with a checkpoint inhibitor are at increased risk for infection, either from immune dysregulation, medication-induced neutropenia, or from immunosuppression associated with the management of IRAEs. In this paper, we examine these phenomena and explore how the risk of infectious might be mitigated through the use of antimicrobial prophylaxis in high-risk patients.
Expert commentary: There is no prospective data on thee toxicities associated with checkpoint inhibition, and guidelines are currently based on symptomatic management from the ongoing clinical trials. As the field of cancer immunotherapy moves forward, checkpoint inhibitors will be combined with other anti-neoplastic treatments and a crucial next step will be to further clarify the ways in which checkpoint inhibitors predispose patients to infection to establish guidelines for antimicrobial prophylaxis.
Declaration of Interest
MW McCarthy has served as a paid consultant to Allergan. TJ Walsh receives research grants for experimental and clinical antimicrobial pharmacotherapeutics from Astellas, Cubist, Theravance, the Medicines Company, Allergan, Novartis, Merck, and Pfizer. He has served as consultant to Astellas, Actavis, ContraFect, Drais, iCo, Novartis, Pfizer, Methylgene, SigmaTau, and Trius. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.