Impact of Clonal Hematopoiesis–Associated Mutations in Phase I Patients Treated for Solid Tumors: An Analysis of the STING Trial
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- ISIDORE Id: 10670/1.2cb93d...
- inserm-04981546
- doi: 10.1200/PO.23.00631
- PUBMED: 38815178
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clonal hematopoiesis epigenetic modifiers solid tumors phase I clinical trials -bio]/CancerCiter ce document
Julieta Rodriguez et al., « Impact of Clonal Hematopoiesis–Associated Mutations in Phase I Patients Treated for Solid Tumors: An Analysis of the STING Trial », HAL SHS (Sciences de l’Homme et de la Société), ID : 10.1200/PO.23.00631
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PURPOSE With liquid biopsy's widespread adoption in oncology, an increased number of clonal hematopoiesis–associated mutations (CHm) have been identified in patients with solid tumors. However, its impact on patient outcomes remains unclear. This study aimed to analyze and describe CHm in a cohort of phase I patients. METHODS Retrospective data collection from medical records and molecular profiles (Foundation One Liquid CDx Assay) was performed before first study drug administration at the Drug Development Department of Gustave Roussy (France) within the STING trial (ClinicalTrials.gov identifier: NCT04932525 ). CHm prevalence was assessed using any and ≥1% variant allele frequency (VAF) in epigenetic modifier genes ( DNMT3A, TET2, and ASXL1). RESULTS From January 2021 to December 2022, 255 patients were enrolled in a phase I clinical trial. A total of 55% were male, with a median age of 62 years (24-86). Principal tumor locations were GI (27%) and genitourinary (21%). Overall, 104 patients (41%) had at least one CHm in liquid biopsy, with 55 patients (22%) having a VAF of ≥ 1%. The most frequent mutation was DNMT3A 73% at any VAF (n = 76) and 22% at 1% VAF (n = 23). Median progression-free survival (PFS) and overall survival were 3.8 months (m) for the CHm group versus 3.2 m for nonclonal hematopoiesis (CH; P = .08) and 18.26 m CHm versus 15.8 m non-CH ( P = .9), respectively. PFS increased in the CHm population treated with targeted therapy (hazard ratio, 0.6 [95% CI, 0.42 to 0.84]; P = .004). CONCLUSION CHm was commonly found in patients with solid tumors treated in phase I trials, with a prevalence of 41% in our cohort. The most frequently mutated gene was DNMT3A. The presence of CHm had no impact on the population of patients treated in the phase I trials.
