Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria

TLDR

Immunotherapeutic agents elicit antitumor immune responses, producing response patterns that can include initial tumor growth or new lesions, which are not fully captured by conventional RECIST or WHO criteria designed for cytotoxic therapies. The study sought to develop immune‑related response criteria that better reflect the diverse response patterns of immunotherapy, using the extensive ipilimumab phase II melanoma data set. The authors derived criteria from community workshops and evaluated them on ipilimumab phase II trials, identifying four distinct response patterns: lesion shrinkage without new lesions, durable stable disease, delayed response after tumor increase, and response despite new lesions. All four patterns were linked to favorable survival, supporting the utility of the proposed immune‑related response criteria for assessing immunotherapy outcomes.

Abstract

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.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.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.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.