PT  - JOURNAL ARTICLE
AU  - Harriet Kluger
AU  - J Carl Barrett
AU  - Justin F Gainor
AU  - Omid Hamid
AU  - Michael Hurwitz
AU  - Theresa LaVallee
AU  - Rebecca A Moss
AU  - Roberta Zappasodi
AU  - Ryan J Sullivan
AU  - Hussein Tawbi
AU  - Elad Sharon
TI  - Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors
AID  - 10.1136/jitc-2022-005921
DP  - 2023 Mar 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e005921
VI  - 11
IP  - 3
4099  - http://jitc.bmj.com/content/11/3/e005921.short
4100  - http://jitc.bmj.com/content/11/3/e005921.full
SO  - J Immunother Cancer2023 Mar 01; 11
AB  - Immunotherapy is the standard of care for several cancers and the field continues to advance at a rapid pace, with novel combinations leading to indications in an increasing number of disease settings. Durable responses and long-term survival with immunotherapy have been demonstrated in some patients, though lack of initial benefit and recurrence after extended disease control remain major hurdles for the field. Many new combination regimens are in development for patients whose disease progressed on initial immunotherapy. To guide clinical trial design and support analyses of emerging molecular and cellular data surrounding mechanisms of resistance, the Society for Immunotherapy of Cancer (SITC) previously generated consensus clinical definitions for resistance to single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) in three distinct scenarios: primary resistance, secondary resistance, and progression after treatment discontinuation. An unmet need still exists, however, for definitions of resistance to ICI-based combinations, which represent an expanding frontier in the immunotherapy treatment landscape. In 2021, SITC convened a workshop including stakeholders from academia, industry, and government to develop consensus definitions for resistance to ICI-based combination regimens for improved outcome assessment, trial design and drug development. This manuscript reports the minimum drug exposure requirements and time frame for progression that define resistance in both the metastatic setting and the perioperative setting, as well as key caveats and areas for future research with ICI/ICI combinations. Definitions for resistance to ICIs in combination with chemotherapy and targeted therapy will be published in companion volumes to this paper.