Abstract 508P
Background
CHIP refers to the finding of one or more mutations affecting genes involved in hematological malignancies in patients (pts) without hematological disease per se. The main risk factor for developing CHIP is aging. An increased risk of developing CHIP has been recently identified in pts with solid tumors. Comprehensive data integrating the molecular and clinical characteristics of pts with solid tumors and CHIP remain limited.
Methods
This study aims to calibrate the prevalence of CHIP-related mutations (CHIPm) through liquid biopsy performed in pts aged from 70 years old onwards enrolled in a phase I study. We collected retrospectively data from medical records and molecular profile (Foundation One Liquid CDx Assay) reports performed from January to December 2021, before first study drug administration at the Drug Development Department at Gustave Roussy within the STING trial (NCT04932525). We selected the 4 following CHIPm; DNMT3A, TET2, ASXL1 and JAK2, as these genes are not considered directly related to solid tumors. CHIP prevalence was assessed according to two allele frequency (VAF) thresholds (1% and 2%).
Results
53 pts were included; 74% were male and median age was 74 years. All pts previously received treatment for solid tumors with a median of 3 prior lines. Most common tumor types were: gastrointestinal (40%), genitourinary (25%), thorax (12%), endocrine system (9%) and skin (7%). Overall, 36 of the 53 pts (68%) had at least 1 CHIPm. VAF at 1% and 2% for each mutation were: DNMT3A 40% and 38%, TET2 33% and 39%, ASXL1 20% and 22%, JAK2: 7% and 9%. 21 of the 53 pts (58%) had more than 1 CHIPm. Median progression free survival (PFS) from CHIPm pts compared to pts without CHIPm was 4.1 months (m) versus (vs) 3.1m (p=0.1669), respectively; PFS in CHIPm-pts with VAF 1% vs no-CHIPm pts were 5.9 and 2.6m (p=0.1130); PFS in pts with CHIPm with VAF 2% vs no-CHIPm pts were 4.1 and 3.9m (p=0.6041). Overall survival (OS) for pts with CHIPm vs no-CHIP was 5.5 and 6.6m, respectively (p=0.9290); CHIP VAF 1%: NR; CHIP VAF 2%: 5 m.
Conclusions
CHIP are commonly found in elderly pts with a solid tumor, with a prevalence in our cohort of 68%. No patient developed a characterized hematological disease and no differences in outcomes were identified.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gustave Roussy Institute.
Funding
Has not received any funding.
Disclosure
A. Bayle: Non-Financial Interests, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, ; Financial Interests, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Other: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. E. Rouleau: Financial Interests, Advisory Role: AstraZeneca, Roche Diagnostics, and BMS; Financial Interests, Other: AstraZeneca and BMS. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, EISAI; Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm; 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: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seattle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Tahio; 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. J. Michot: Non-Financial Interests, Principal Investigator: AbbVie, Agios, Amgen, Argen-x, Astex, AstraZeneca, Beigene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Jan; Financial Interests, Other: Roche, AstraZeneca, Amgen.; Non-Financial Interests, Other: Celgene, Bristol Myers Squibb, GSK. S. Champiat: Financial Interests, Advisory Board: : Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Ellipses Pharma, Oncovita, Seagen, UltraHuman; Non-Financial Interests, Principal Investigator: AbbVie, Amgen, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners Ag, MSD, Ose Pharma, Pierre Fabre, Sanofi Aventis, Sotio A.S, Transgene; Financial Interests, Other: Amgen, Astellas, AstraZeneca, BMS, Eisai, Genmab, Janssen, MSD, Novartis and Roche., AstraZeneca, MSD, Ose Pharma, Roche, Sotio. A. Marabelle: Financial Interests, Advisory Board: BMS, MSD, AZ, Roche/Genentech, Novartis, Merck Serono, Pfizer and Sanofi. ; Financial Interests, Research Grant: Fondation MSD Avenir, Sanofi, MSD, BMS, Roche/Genentech and Boehringer Ingelheim. S. Postel-Vinay: Financial Interests, Advisory Role: Merck KGaA.; Non-Financial Interests, Principal Investigator: AbbVie, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare AG, Bbb Technologies BV, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Chugai Pharmac; Financial Interests, Funding: Merck KGaA, Boehringer Ingelheim and Roche. C. Marzac: Financial Interests, Other: Astellas. S. Ponce: Financial Interests, Advisory Role: Roche; Financial Interests, Speaker’s Bureau: Bristol Myers Squibb, ; Financial Interests, Other: RSD Pharma. A. Italiano: Financial Interests, Other: Bayer, Daiichi Sankyo, Lilly, Epizyme, Novartis, Roche, IPSEN; Financial Interests, Advisory Role: Roche, Daiichi Sankyo, Immune Design, Epizyme, Bayer, Lilly; Financial Interests, Funding: Roche, Bayer, AstraZeneca/MedImmune, PharmaMar, MSD Oncology, Merck Serono. J. Baptiste Micol: Financial Interests, Advisory Role: AbbVie, Jazz Pharmaceuticals. C. Baldini: Other, Advisory Board: Bicycle therapeutics, Rising Tide Fundation, ITEOS; Financial Interests, Other: : GSK, BMS, AZ, Amgen, Sanofi, MSD travel acomodation; Financial Interests, Funding: BMS Fundation; Financial Interests, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Other: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche (drug supplied); Non-Financial Interests, 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. All other authors have declared no conflicts of interest.