Thinking critically about classifying adverse events: Incidence of pancreatitis in patients treated with nivolumab + ipilimumab Academic Article uri icon


MeSH Major

  • Amylases
  • Antineoplastic Combined Chemotherapy Protocols
  • Lipase
  • Melanoma
  • Pancreatitis


  • The Common Terminology Criteria for Adverse Events (CTCAE) were developed to document the adverse effects of chemotherapy but are now also used to document immune-related adverse events (irAE). Characterization of irAE by the CTCAE has implications for determining dose-limiting toxicity (DLT) and, consequently, the recommended phase II dose (RP2D) of investigational agents. In the phase I trial of nivolumab + ipilimumab, an asymptomatic increase in lipase was the primary DLT that informed the RP2D. We performed a retrospective study of 119 patients with melanoma who were treated at Memorial Sloan Kettering Cancer Center with the combination of nivolumab + ipilimumab to investigate the relationship between asymptomatic grade 3 or higher increases in amylase and/or lipase and pancreatitis, a known irAE. Of the 119 patients, there were only two cases of pancreatitis, representing 20% of patients with grade 3 or higher amylase, 6.3% of patients with grade 3 or higher lipase, and 20% of patients with grade 3 or higher elevations of both enzymes. The application of the CTCAE, especially in grading independent lab values, should be considered carefully in clinical trials of novel immunotherapeutic agents.

publication date

  • January 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5441295

Digital Object Identifier (DOI)

  • 10.1093/jnci/djw260

PubMed ID

  • 28040701

Additional Document Info


  • 109


  • 4