Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria.
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.
Wolchok
Jedd D
JD
Ludwig Center for Cancer Immunotherapy and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. wolchokj@mskcc.org
Hoos
Axel
A
O'Day
Steven
S
Weber
Jeffrey S
JS
Hamid
Omid
O
Lebbé
Celeste
C
Maio
Michele
M
Binder
Michael
M
Bohnsack
Oliver
O
Nichol
Geoffrey
G
Humphrey
Rachel
R
Hodi
F Stephen
FS
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
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D000074324:Ipilimumab