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. 2023 Mar;11(3):e005920.
doi: 10.1136/jitc-2022-005920.

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

Naiyer Rizvi  1 , Foluso O Ademuyiwa  2 , Z Alexander Cao  3 , Helen X Chen  4 , Robert L Ferris  5 , Sarah B Goldberg  6 , Matthew D Hellmann  7 , Ranee Mehra  8 , Ina Rhee  9 , Jong Chul Park  10 , Harriet Kluger  6 , Hussein Tawbi  11 , Ryan J Sullivan  12
Affiliations

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

Naiyer Rizvi et al. J Immunother Cancer. 2023 Mar.

Abstract

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop responding to treatment with immunotherapy combinations, however, is challenging without uniform definitions of resistance. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-programmed cell death protein 1 (PD-1). To provide guidance for clinical trial design and to support analyses of emerging molecular and cellular data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of ICIs and chemotherapies. Definitions for resistance to ICIs in combination with targeted therapies and with other ICIs will be published in companion volumes to this paper.

Keywords: Drug Therapy, Combination; Immunotherapy; Tumor Escape.

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Conflict of interest statement

Competing interests: NR—Salary and employment: Synthekine; Royalty: Personal genome Diagnostics; IP Rights: Determinants of cancer response to immunotherapy (PCT/US2015/062208); Ownership interest less than 5%: Gritstone Bio, Synthekine. ZAC—Salary and employment: Merck; Ownership interest less than 5%: Merck. FOA—Consulting fees: Teladoc Health, Pfizer, AstraZeneca, QED Therapeutics, Immunomedics, Cardinal Health, Athenex, Biotheranostics; Contracted research: Pfizer, Immunomedics, NeoImmuneTech, RNA Diagnostics, Astellas Pharma. IR—Salary and employment: Genentech/Roche; Ownership interest less than 5%: Roche. JCP—Consulting fees: Merck, ABL Bio, MitoImmune, I-Mab. MDH—After completion of this manuscript, became an employee (with equity) of AstraZeneca. Salary and employment: AstraZeneca (after completion of this manuscript); IP rights: A patent filed by his institution related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx; Consulting fees: Merck, Bristol Myers Squibb, AstraZeneca, Genentech/Roche, Nektar, Syndax, Mirati, Shattuck Labs, Immunai, Blueprint Medicines, Achilles, Arcus, PACT, Regeneron/Sanofi, Janssen, Natera, Instil Bio; Contracted research: Bristol Myers Squibb; Ownership interest less than 5%: Arcus, Immunai, Shattuck labs, Factorial, Avail, and AstraZeneca (after completion of this manuscript). RM—Consulting fees: Bayer, Rakuten Medical, Coherus, AstraZeneca (uncompensated); Research funds: AstraZeneca, Merck. RLF—Consulting fees: Achilles Therapeutics, Aduro Biotech, Bicara Therapeutics, Bristol Myers Squibb, Brooklyn Immunotherapeutic, Everest Clinical Research Corporation, F. Hoffman-La Roche Ltd, Genocea Biosciences, Hookipa Biotech GmbH, Instill Bio, Kowa Research Institute, Lifescience Dynamics Limited, MacroGenics, Merck, Mirati Therapeutics, Nanobiotix, Novasenta, Numab Therapeutics AG, OncoCyte Corporation, Pfizer, PPD Development, L.P., Rakuten Medical, Sanofi, Seagen, Vir Biotechnology, Zymeworks; Contracted research: AstraZeneca/MedImmune, Bristol Myers Squibb, Merck, Novasenta, Tesaro; Shares owned: Novasenta. SBG—Consulting fees: AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, Boehringer Ingelheim, Genentech, Mirati Therapeutics, Sanofi Genzyme, Daiichi-Sankyo, Regeneron, Takeda, Janssen; Contracted research: AstraZeneca, Boehringer Ingelheim. HK—Consulting fees: Iovance, Immunocore, Celldex, Array Biopharma, Merck, Elevate Bio, Instil Bio, Bristol Myers Squibb, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero. 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. RJS—Consulting fees: Asana Biosciences, AstraZeneca, Bristol Myers Squibb, Eisai, Iovance, Merck, Novartis, OncoSec, Pfizer, Replimune; Contracted research: Merck, Amgen. HXC—Nothing to disclose. SITC Staff: SMW, CG, PJI—Nothing to disclose.

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