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

Abstract

Purpose: Immunotherapeutic agents produce antitumor effects by inducing cancerspecific 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. Experimental Design: 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. Conclusion: 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. (Clin Cancer Res 2009;15(23):7412-20)

Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma

“…Non-responding tumors were derived from patients who had progressive disease. These response patterns were based on irRECIST (Hoos et al, 2015;Wolchok et al, 2009). We also analyzed the transcriptomes through RNASeq of responding (n=15) and non-responding (n=13) pretreatment tumors (total 27 of 28 pretreatment; 1 of 28 early ontreatment) with available high-quality RNA.…”

Challenges and Opportunities in Dose Finding in Oncology and Immuno‐oncology

“…However, for the recent IO therapies, the dynamics of tumor response to treatment appears to be different with other MOAs. Response patterns with IO are potentially diverse, with delayed responses, and even an initial increase in tumor burden or appearance of new lesions before regression (pseudo‐progression) 35. In addition, IO therapies may lead to more long‐term efficacy, as exemplified by more substantial OS separation at late times.…”

Nouvelles pratiques en immuno-oncologie : une révolution et un immense défi scientifique et médical

“…Ce phénomène, qui n'est pas observé avec les thérapies ciblées (où l'échappe-ment thérapeutique est inéluctable), illustre parfaitement la réponse mémoire induite par ces immunothérapies, ainsi que la capacité d'adaptation du système immunitaire à l'émergence de nouveaux clones tumoraux. Une particularité de ces immunothérapies est le profil parfois atypique des réponses observées, plus complexe que celui obtenu avec les thérapeutiques conventionnelles [1]. En effet, un phé-nomène de « pseudo-progression », au cours duquel la tumeur grossit initialement mais finit par régresser en réponse au traitement, a été décrit.…”