title: Thinking Critically About Classifying Adverse Events: Incidence of Pancreatitis in Patients Treated With Nivolumab + Ipilimumab.
abstract: 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.
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Claire F
authors.initials: CF
authors.lastname: Friedman
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Varina
authors.initials: V
authors.lastname: Clark
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Raikhel
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Tim
authors.initials: T
authors.lastname: Barz
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shoushtari
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Parisa
authors.initials: P
authors.lastname: Momtaz
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hellmann
authors.affiliation: Affiliations of authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY (CFF, VC, TB, ANS, PM, MKC, JDW, PBC, MDH, MAP); Weill Cornell Medical College, New York, NY (CFF, AVR, ANS, PM, MKC, JDW, PBC, MDH, MAP).
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
mesh_terms: D000681:Amylases / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008049:Lipase / Q000097:blood*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D000077594:Nivolumab; D010195:Pancreatitis / Q000097:blood* / Q000139:chemically induced*; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D000077594:Nivolumab; D008049:Lipase; D000681:Amylases