title: New-onset toxicity with programmed death-1 inhibitor rechallenge.
abstract: Immunotherapy has become a mainstay in the treatment of metastatic melanoma. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors and programmed death-1 (PD-1) inhibitors, which have been added more recently, represent two of the main classes of immunomodulating agents. PD-1 inhibitors are well tolerated and are known to have a decreased rate of occurrence of adverse effects compared with CTLA-4 inhibitors. However, the risk remains for serious immune-mediated adverse reactions. Given their long half and extended efficacy, treatment with a CTLA-4 inhibitor before use of a PD-1 inhibitor may increase the risk of adverse effects. In addition, caution should be exercised when rechallenging grade 3 or 4 adverse effects with the same agent or a different agent of the same class. The re-emergence of a previous toxicity may occur or, as found in this case, a new severe effect may arise. This article will present a case of fatal immune-related hepatoxicity in a patient treated with a CTLA-4 inhibitor, followed by treatment with a PD-1 inhibitor. The mechanisms of action and safety profiles for both classes of drugs will also be reviewed.
authors.affiliation: Department of Pharmacy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Ludlow
authors.forename: Stephanie
authors.initials: S
authors.lastname: Andrews
authors.forename: Yanina
authors.initials: Y
authors.lastname: Pasikhova
authors.forename: Eboné
authors.initials: E
authors.lastname: Hill
mesh_terms: D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000473:pathology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D061026:Programmed Cell Death 1 Receptor