title: Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.
abstract: OBJECTIVE
  Retrospective analysis of irAEs in melanoma patients treated with nivolumab.
  
  
  METHODS
  Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs.
  
  
  RESULTS
  IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P ≤ 0.001), and OS benefit was noted in patients who reported three or more irAE events (P ≤ 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis).
  
  
  CONCLUSIONS
  Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.
authors.affiliation: Department of Graduate Medical Education, University of South Florida, Tampa, Florida. morganna.freemankeller@moffitt.org.
authors.forename: Morganna
authors.initials: M
authors.lastname: Freeman-Keller
authors.affiliation: Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Youngchul
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Heather
authors.initials: H
authors.lastname: Cronin
authors.affiliation: Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Allison
authors.initials: A
authors.lastname: Richards
authors.affiliation: Department of Cutaneous Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Gibney
authors.affiliation: Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D052016:Mucositis / Q000139:chemically induced; D015999:Multivariate Analysis; D000077594:Nivolumab; D011014:Pneumonia / Q000139:chemically induced; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab