title: Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria.
abstract: OBJECTIVE
  Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes. Resulting clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions (progressive disease). Response Evaluation Criteria in Solid Tumors or WHO criteria, designed to detect early effects of cytotoxic agents, may not provide a complete assessment of immunotherapeutic agents. Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required.
  
  
  METHODS
  The phase II clinical trial program with ipilimumab, an antibody that blocks CTL antigen-4, represents the most comprehensive data set available to date for an immunotherapeutic agent. Novel immune therapy response criteria proposed, based on the shared experience from community workshops and several investigators, were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma.
  
  
  RESULTS
  Ipilimumab monotherapy resulted in four distinct response patterns: (a) shrinkage in baseline lesions, without new lesions; (b) durable stable disease (in some patients followed by a slow, steady decline in total tumor burden); (c) response after an increase in total tumor burden; and (d) response in the presence of new lesions. All patterns were associated with favorable survival.
  
  
  CONCLUSIONS
  Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria. Further prospective evaluations of the immune-related response criteria, particularly their association with overall survival, are warranted.
authors.affiliation: Ludwig Center for Cancer Immunotherapy and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. wolchokj@mskcc.org
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Celeste
authors.initials: C
authors.lastname: Lebbé
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Michael
authors.initials: M
authors.lastname: Binder
authors.forename: Oliver
authors.initials: O
authors.lastname: Bohnsack
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Nichol
authors.forename: Rachel
authors.initials: R
authors.lastname: Humphrey
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000592:standards*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012878:Skin Neoplasms / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D000074324:Ipilimumab