Abstract 169P
Background
CH refers to the presence of somatic mutations charged to hematopoietic cells, potentially causing clonal expansion. We explored characteristics of CH in patients with NSCLC through liquid biopsy (LB) analysis.
Methods
We retrospectively reviewed LB profiles of patients with NSCLC performed in 2021 at Gustave Roussy. Patients signed an inform consent for the STING protocol (NCT04932525). To minimize the overestimation of CH, we assessed pathogenic mutations in genes extensively reported to be related to hematologic disorders (ASXL1, DNMT3A, TET2). All results were centrally reviewed at Gustave Roussy Molecular Tumor Board. NGS on plasma samples was performed by FoundationOne Liquid CDx. Descriptive analyses were done.
Results
355 LB were collected from 290 patients; 142 (49%) were female, 272 (94%) had a metastatic disease and received a median of 2 lines of treatment (range 1-14). The median age was 64 years (IQR 55-71). Nine LB (3%) were performed in patients with non-metastatic tumors, 39 (11%) and 82 (23%) before and at progression to first-line treatment, respectively, while the 63% during further lines of therapy. Overall, 232 mutations were found in ASXL1 and/or DNMT3A and/or TET2 with a median allele fraction (mAF) of 0.96%, in 146 LB from 143 patients (49%). ASXL1 mutations were detected in 9% of patients (mAF 1.34%), predominantly the p.(Gly646Trpfs*12) variant. DNMT3A mutations were detected in 99 patients (34%) (mAF 0.85%), being p.(Arg882His) and p.(Arg736Cys) the most common variants. Mutations in TET2 were found in 15% of patients (n=44), with a mAF of 1.02%. There was a positive correlation between the frequency of detection of CH and age of patients: 30% in patients <60 years, 55% in aged 60 to 70, and 57% in those >70 years (χ2 p <0.0001). The mAF was higher in elderly patients: 0.74% vs. 1.05% vs. 1.15%, respectively. No correlation was observed between the prevalence of CH and the number of systemic treatment lines received.
Conclusions
Mutations of ASXL1, DNMT3A, TET2 in LB are a common finding in patients with NSCLC. Characteristics and value of CH are currently being assessed in further studies.
Legal entity responsible for the study
Gustave Roussy.
Funding
Has not received any funding.
Disclosure
M. Tagliamento: Non-Financial Interests, Personal, Other, Travel grants: Roche, Bristol Myers Squibb, Astra Zeneca, Takeda; Other, Personal, Writing Engagements, Honoraria as medical writer: Novartis, Amgen. B. Besse: Other, Institutional, Sponsor/Funding, Sponsored Research at Gustave Roussy : 4D Pharma, Abbvie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genen. All other authors have declared no conflicts of interest.