title: Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody.
abstract: OBJECTIVE
  Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective.
  
  
  METHODS
  Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy.
  
  
  RESULTS
  A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti-PD-1 therapy.
  
  
  CONCLUSIONS
  These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. evanlipson@jhmi.edu
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Lipson
authors.forename: William H
authors.initials: WH
authors.lastname: Sharfman
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.forename: Ira
authors.initials: I
authors.lastname: Wollner
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Alice
authors.initials: A
authors.lastname: Pons
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab