Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors.

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.

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: HK—consulting fees: Iovance, Immunocore, Celldex, Array Biopharma, Merck, Elevate Bio, Instil Bio, Bristol Myers Squibb, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero. JCB—salary and employment: AstraZeneca; Ownership interest less than 5%: AstraZeneca. JFG—consulting fees: Bristol-Myers Squibb, Genentech/Roche, Takeda, Loxo/Lilly, Blueprint, Oncorus, Regeneron, Gilead, Mirati, Moderna, AstraZeneca, Pfizer, Novartis, Merck, iTeos, Karyopharm, Jazz Pharmaceuticals, Silverback Therapeutics, and GlydeBio; Contracted research: Novartis, Genentech/Roche, Takeda, Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo; Ownership interest less than 5%: Ironwood Pharmaceuticals; Spousal employment: Ironwood Pharmaceuticals. MH—consulting fees: Bristol Myers Squibb, CRISPR Therapeutics, Exelixis, Nektar Therapeutics, Janssen; Spousal employment: Arvinas. OH—consulting fees: Aduro, Akeso, Amgen, Beigene, Bioatla, Bristol Myers Squibb, Genentech/Roche, GSK, Immunocore, Idera, Incyte, Iovance, Instil Bio, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi Regeneron, SeaGen, Tempus, Zelluna; Fees for non-CME services: Bristol Myers Squibb, Novartis, Pfizer, Sanofi Regeneron; Contracted research: Arcus, Aduro, Akeso, Amgen, Bioatla, Bristol Myers Squibb, Cytomx, Exelixis, Genentech/Roche, GSK, Immunocore, Idera, Incyte, Iovance, Merck, Moderna, Merck Serono, NextCure, Novartis, Pfizer, Rubius, Sanofi Regeneron, SeaGen, Torque, Zelluna. RAM—salary and employment: Bristol Myers Squibb; Ownership interest less than 5%: Bristol Myers Squibb. RZ—IP rights: Memorial Sloan Kettering, Weill Cornell Medical College; Consulting fees: Leap Therapeutics, iTEOS. TL—Salary and employment: Coherus Biosciences; IP rights: AstraZeneca, Parker Institute for Cancer Immunotherapy, Celldex, EntreMed; Consulting fees: TRex Bio, Grey Wolf Therapeutics, Exosis, LisCure Biosciences, BiOne Cure, Inovio, 1440 Foundation; Ownership interest less than 5%: AstraZeneca, Coherus Biosciences. RJS—consulting fees: Asana Biosciences, AstraZeneca, Bristol Myers Squibb, Eisai, Iovance, Merck, Novartis, OncoSec, Pfizer, Replimune; Contracted research: Merck, Amgen. HT—consulting fees: Genentech/Roche, Bristol Myers Squibb, Novartis, Merck, Pfizer, Eisai, Karyopharm, Boxer Capital; Contracted research: Genentech/Roche, Bristol Myers Squibb, Novartis, Merck, GSK. ES—nothing to disclose. SITC Staff: SMW, CG, PJI—nothing to disclose.