Immune-Related Response Criteria

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ('respond'), stay the same ('stabilize'), or worsen ('progress') during treatment, where the compound being evaluated is an immuno-oncology drug. Immuno-oncology, part of the broader field of cancer immunotherapy, involves agents which harness the body's own immune system to fight cancer. Traditionally, patient responses to new cancer treatments have been evaluated using two sets of criteria, the WHO criteria and the response evaluation criteria in solid tumors (RECIST). The immune-related response criteria, first published in 2009, arose out of observations that immuno-oncology drugs would fail in clinical trials that measured responses using the WHO or RECIST Criteria, because these criteria could not account for the time gap in many patients between initial treatment and the apparent action of the immune system to reduce the tumor burden. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ('respond'), stay the same ('stabilize'), or worsen ('progress') during treatment, where the compound being evaluated is an immuno-oncology drug. Immuno-oncology, part of the broader field of cancer immunotherapy, involves agents which harness the body's own immune system to fight cancer. Traditionally, patient responses to new cancer treatments have been evaluated using two sets of criteria, the WHO criteria and the response evaluation criteria in solid tumors (RECIST). The immune-related response criteria, first published in 2009, arose out of observations that immuno-oncology drugs would fail in clinical trials that measured responses using the WHO or RECIST Criteria, because these criteria could not account for the time gap in many patients between initial treatment and the apparent action of the immune system to reduce the tumor burden. Part of the process of determining the effectiveness of anti-cancer agents in clinical trials involves measuring the amount of tumor shrinkage such agents can generate. The WHO Criteria, developed in the 1970s by the International Union Against Cancer and the World Health Organization, represented the first generally agreed specific criteria for the codification of tumor response evaluation. These criteria were first published in 1981. The RECIST criteria, first published in 2000, revised the WHO criteria primarily to clarify differences that remained between research groups. Under RECIST tumour size was measured unidimensionally rather than bidimensionally, fewer lesions were measured, and the definition of 'progression' was changed so that it was no longer based on the isolated increase of a single lesion. RECIST also adopted a different shrinkage threshold for definitions of tumour response and progression. For the WHO Criteria it had been >50% tumour shrinkage for a Partial Response and >25% tumour increase for Progressive Disease. For RECIST it was >30% shrinkage for a Partial Response and >20% increase for Progressive Disease. One outcome of all these revisions was that more patients who would have been considered 'progressors' under the old criteria became 'responders' or 'stable' under the new criteria. RECIST and its successor, RECIST 1.1 from 2009, is now the standard measurement protocol for measuring response in cancer trials. The key driver in the development of the irRC was the observation that, in studies of various cancer therapies derived from the immune system such as cytokines and monoclonal antibodies, the looked-for Complete and Partial Responses as well as Stable Disease only occurred after an increase in tumor burden that the conventional RECIST Criteria would have dubbed 'Progressive Disease'. Basically, RECIST failed to take account of the delay between dosing and an observed anti-tumour T cell response, so that otherwise 'successful' drugs - that is, drugs which ultimately prolonged life - failed in clinical trials. This led various researchers and drug developers interested in cancer immunotherapy such as Axel Hoos at Bristol-Myers Squibb (BMS) to start discussing whether a new set of response criteria ought to be developed specifically for immmuno-oncology drugs. Their ideas, first flagged in a key 2007 paper in the Journal of Immunotherapy, evolved into the immune-related response criteria (irRC), which was published in late 2009 in the journal Clinical Cancer Research.