2171P - Incidence of adverse events in patients treated with a combination of immune checkpoint blockers and chemotherapy: A real life cohort

Background

Chemotherapy combined with immune checkpoint blockers (ICB) is now the standard of care for treatment in multiple advanced tumor types with two spectrums of adverse events related to cytotoxic agents and immune related (irAEs). Clinical manifestations of irAEs can mimic chemotherapy toxicity in several aspects while the management remains completely different.

Methods

We conducted a retrospective review of the medical records for patients with metastatic cancers treated with chemo-immunotherapy combinations at Gustave Roussy Cancer Center from Sep 1^st 2020 to Dec 31^st 2022, included in the REISAMIC database (Registry of Severe Adverse Reactions to Immunomodulatory Monoclonal Antibodies in Cancer). Adverse events are reported according to the Common Terminology Criteria for Adverse Events v5.0.

Results

Our cohort includes 261 patients with a median age of 64 years [30-93], 79% of patients with lung cancer, 9% triple- negative breast cancer; 8.5% head and neck carcinoma, and 2.5% upper digestive tract tumors. Treatment discontinuation rate for toxicity was 11% in our cohort; we also reported five toxic deaths. A total of 83% of the patients presented all grade adverse events, with 38% grade ≥3 toxicities most commonly hematological. Out of all the adverse events (AEs), 53.4% were attributed to chemotherapy while 15.4% were considered irAEs. Median days until chemotherapy induced AEs was 40 days and the majority resolved in ≤2 weeks, while median days until irAEs was 105 days and the majority required 2-12 weeks until resolution. AEs of special interest included one case of myocarditis, 2 cases of hypophysitis, thyroid disorder in 25 patients, 2 cases of immune mediated diabetes revealed by diabetic ketoacidosis, and 9 cases of autoimmune hepatitis.The relapse rate after immunotherapy rechallenge was 13%.

Conclusions

In this real-life cohort of patients treated with chemo-immunotherapy we observe a reassuring safety profile concordant with data reported in clinical trials. Expert opinion, radiological exams, histological evidence and biological data were employed to distinguish the implication of either drugs in toxic mechanisms in order to tailor the management, and minimize treatment interruptions.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Aldea: Financial Interests, Personal, Advisory Board: Viatris; Financial Interests, Personal, Royalties: Sandoz; Financial Interests, Institutional, Research Funding: Amgen, AstraZeneca. A. Marabelle: Financial Interests, Personal, Advisory Board: Gritstone, Innate Pharma, Neogene, Deka Biosciences, Hotspot Therapeutics, Johnson & Johnson, Depth Charge, Bioline Rx, Clover Biopharmaceuticals, Grey Wolf Therapeutics, Lytix Biopharma, RedX Pharma, HiFiBiO Therapeutics, ImCheck Therapeutics, Shattuck Labs, Marengo Therapeutics, PegaOne; Financial Interests, Personal, Other, Associate Editor: European Journal of Cancer; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics, Deka Biosciences, HotSpot Therapeutics, Shattuck Labs; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Sanofi; Financial Interests, Institutional, Coordinating PI: IMCheck, SOTIO, Roche/Genentech, MSD, BMS, OSE Immunotherapeutics, Eisai, Pierre Fabre, Adlai Nortye, Molecular Partners; Financial Interests, Steering Committee Member: Roche; Financial Interests, Institutional, Funding: Transgene; Non-Financial Interests, Other, Associate Editor: IOTECH Journal; Non-Financial Interests, Institutional, Product Samples: BMS, IDERA, MSD, Transgene; Non-Financial Interests, Leadership Role: Société Française d'Immunothérapie des Cancers; Non-Financial Interests, Member: Society for Immunotherapy of Cancer, American Association for Cancer Research, American Society for Clinical Oncology; Other, Consultant: Third Rock Ventures, Guidepoint; Other, Advisor: Medicxi. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. S. Champiat: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Merck Serono, Novartis and Roche; Financial Interests, Personal, Other, Principal Investigator of Clinical Trials: AbbVie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Sanofi Aventis, Sotio A.S, Transgene; Financial Interests, Personal, Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Inc., Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, Sotio; Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP) =Principal/sub-Investigator of Clinical Trials: Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Adaptimmune, AdlaiAstex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Incyte Corporation, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D Llc, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP) =Research Grants: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Product Samples, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): AstraZeneca, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216 ; WP42627 ; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, Sanofi. C. Smolenschi: Financial Interests, Institutional, Local PI: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beige. J.T.M.L. Ribeiro: Financial Interests, Personal, Advisory Board: Gilead Sciences, Inc.; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: eESO. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. S. Ponce Aix: Financial Interests, Advisory Board: Roche, MSD, AstraZeneca, Bristol Myers Squibb, PharmaMar, Boehringer Ingelheim, BMS. Expert testimony: Roche, MSD, AstraZeneca, Bristol Myers Squibb, PharmaMar, Boehringer Ingelheim, BMS. Travel, accommodations, expenses: MSD, Roche, BMS, AstraZeneca, Ph; Financial Interests, Invited Speaker: Bristol Myers Squibb. C. Baldini: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beige; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Bicycle therapeutics, Rising Tide Fundation, ITEOS; Financial Interests, Personal and Institutional, Royalties: GSK, BMS, AZ, Amgen, Sanofi, MSD travel accommodation; Financial Interests, Institutional, Research Grant: BMS Fundation, AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Product Samples: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. All other authors have declared no conflicts of interest.