Clonal Hematopoiesis in Whole-Blood and Cell-Free DNA of Ovarian Cancer Patients Undergoing PARP-Inhibitor Treatment: An Exploratory Analysis of the ENGOT-ov48/Eudario Trial

Clonal hematopoiesis (CH), characterized by the expansion of somatically mutated hematopoietic stem cells, is an age-related phenomenon associated with the development of hematologic malignancies, increased cardiovascular risk, and other age-related proinflammatory conditions. In patients with solid tumors, cytotoxic therapies differentially select for clones with mutations in the DNA damage response (DDR) pathway, i.e. TP53and PPM1D, leading to an elevated risk for therapy-related myeloid malignancies (t-MNs). Poly(ADP-ribose) polymerase inhibitors (PARPi) are frequently used to treat ovarian cancer with particularly high efficacy reported in tumors exhibiting homologous recombination (HR) deficiency caused by mutations in BRCA1/2or other HR pathway genes. However, recent data indicate that PARPi treatment is also associated with an elevated risk for t-MNs.