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. 2023 Mar;11(3):e006398.
doi: 10.1136/jitc-2022-006398.

Society for Immunotherapy of Cancer (SITC) consensus definitions for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology

Jarushka Naidoo  1   2   3 , Catherine Murphy  4   5 , Michael B Atkins  6 , Julie R Brahmer  7 , Stephane Champiat  8 , David Feltquate  9 , Lee M Krug  10 , Javid Moslehi  11 , M Catherine Pietanza  12 , Joanne Riemer  13 , Caroline Robert  8   14 , Elad Sharon  15 , Maria E Suarez-Almazor  16 , Karthik Suresh  7 , Michelle Turner  17 , Jeffrey Weber  18 , Laura C Cappelli  19
Affiliations

Society for Immunotherapy of Cancer (SITC) consensus definitions for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology

Jarushka Naidoo et al. J Immunother Cancer. 2023 Mar.

Abstract

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

Keywords: Guidelines as Topic; Immunotherapy; Self Tolerance.

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Conflict of interest statement

Competing interests: JN—Consulting fees: AstraZeneca, Bristol Myers-Squibb, Roche/Genentech, Takeda, Pfizer, Daiichi Sankyo; Contracted research: AstraZeneca, Merck; Data Safety Monitoring Board: Daiichi Sankyo; NPI: 1710327721. LCC—Consulting fees: AbbVie; Contracted research: Bristol-Myers Squibb. CM—Nothing to Disclose. MBA—Consulting fees: Aveo, BMS, Eisai, Exelixis, Genentech, Iovance, Merck, Novartis, Pfizer, Roche, Pyxis, Werewolf, Asher Bio, Calithera, Idera, Agenus, Apexigen, Neoleukin, Adagene, AstraZeneca, Elpis, ScholarRock, Surface, ValoHealth, Sanofi, Fathom; Ownership Interest Less Than 5%: Werewolf, Pyxis, Elpis; NPI: 1306874201. JRB—Consulting fees: Amgen, BMS, Genentech/Roche, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Regeneron; Contracted research: AstraZeneca, BMS, Genentech/Roche, Merck, RAPT Therapeutics, Revolution Medicines; Data and Safety Monitoring Board/Committees: GlaxoSmithKline, Sanofi. SC—Consulting fees: Amgen, AstraZeneca, Ultrahuman, Oncovita; Fees for Non-CE Services: Amgen, AstraZeneca, BMS, Janssen, Merck, MSD, Novartis and Roche; Contracted Research: Amgen, Merck, Sanofi Aventis; As part of the Drug Development Department (DITEP) at Gustave Roussy, Principal/sub-Investigator of Clinical Trials Research Grants from, Non-financial support (drug supplied) from: Principal/sub-Investigator of Clinical Trials for: Abbvie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, XencorResearch Grants from Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi, Non-financial support (drug supplied) from Astrazeneca, Bayer, BMS, Boringher Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. DF—Salary: Palleon Pharmaceuticals; Ownership Interest Less Than 5 Percent: Palleon Pharmaceuticals. LMK—Salary: AstraZeneca; Ownership Interest Less Than 5 Percent: AstraZeneca. JM—Consulting fees: Novartis, Pfizer, Bristol-Myers Squibb, Takeda, Pharmacyclics, Audentes Pharmaceuticals, AstraZeneca, Deciphera, Ipsen, Boston, Biomedical, ImmunoCore, GlaxoSmithKline, Janssen, Myovant, Amgen, Boehringer, Cytokinetics. MCP— Employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA, and own stock (less than 5%) in Merck & Co, Rahway, NJ, US. JR—Nothing to Disclose. CR—Consulting fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, Pfizer, AstraZeneca. ES—NPI: 1467480160. MES-A—Consulting fees: Avenue Therapeutics ChemoCentryx, Celgene (All unrelated to the topic of interest. KS—Nothing to Disclose. MT—Nothing to Disclose. JW—Royalty: Less than 2000 dollars from a TIL growth patent by Moffitt Cancer Center; IP Rights: Named on a PD-1 biomarker patent by Biodesix, and on a CTLA4 biomarker patent by Moffitt Cancer Center, and a TIL growth patent by Moffitt Cancer Center; Consulting fees: Ad Boards for: BMS, GSK, Merck, Genentech, Astra Zeneca, Pfizer, Celldex, Biond, Evaxion, Regeneron, Alkermes, Novartis, Incyte, Moderna, Cytomx, Ultimovacs and Sellas; NPI: 1053348706; Ownership Interest Less Than 5 Percent: Biond, Neximmune MESA: Consultant fees: Pfizer, Eli Lilly, BMS. SITC Staff—CG, AK, NL, SMW: Nothing to Disclose.

Figures

Figure 1
Figure 1
Consensus definitions for irAE terminology. ICI, immune checkpoint inhibitor; IO, immuno-oncology; irAE, immune-related adverse event.
Figure 2
Figure 2
Algorithm for the identification of steroid-unresponsive irAEs. irAE, immune-related adverse event.
See this image and copyright information in PMC

References

    1. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev 2008;224:166–82. 10.1111/j.1600-065X.2008.00662.x - DOI - PubMed
    1. Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 2010;236:219–42. 10.1111/j.1600-065X.2010.00923.x - DOI - PMC - PubMed
    1. de Moel EC, Rozeman EA, Kapiteijn EH, et al. . Autoantibody development under treatment with immune-checkpoint inhibitors. Cancer Immunol Res 2019;7:6–11. 10.1158/2326-6066.CIR-18-0245 - DOI - PubMed
    1. Berner F, Bomze D, Diem S, et al. . Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer. JAMA Oncol 2019;5:1043–7. 10.1001/jamaoncol.2019.0402 - DOI - PMC - PubMed
    1. Kwek SS, Dao V, Roy R, et al. . Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J Immunol 2012;189:3759–66. 10.4049/jimmunol.1201529 - DOI - PMC - PubMed

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