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October 14, 2021

Poly(ADP-Ribose) Polymerase Inhibitors and Myeloid Neoplasm Risk—Clues to a Mechanistic Connection?

Author Affiliations
  • 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Denver
  • 2Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Dartmouth Hitchcock Medical Center, Hanover, New Hampshire
JAMA Oncol. 2021;7(12):1763-1765. doi:10.1001/jamaoncol.2021.4639

Poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPis) have changed the paradigm in epithelial ovarian cancer treatment. The use of PARPis as maintenance therapy after primary platinum-based chemotherapy has reduced the hazards of progression or death by 60% to 70% for women with BRCA-associated cancers, up to 50% in BRCA wild-type and homologous recombination deficient tumors, and up to 32% in homologous recombination proficient tumors.1,2 The American Society of Clinical Oncology Guidelines recommend that PARPis be offered as maintenance therapy to all women with advanced-stage epithelial ovarian cancer in complete or partial response to first-line platinum-based chemotherapy.3 The widespread use of PARPis has resulted in a better understanding of and proficiency in managing the attendant adverse effects and how to optimize patient adherence and quality of life. One of the most consequential risks associated with PARPi use is the development of therapy-related myeloid neoplasms (t-MNs), which occur in 1% to 3% of patients with ovarian cancer.1,2,4,5 The t-MN spectrum includes myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). These secondary malignant cancers are characterized by complex karyotypes, frequent alterations in TP53 (OMIM 191170), and poor prognosis.6 To date, the literature has been inconsistent regarding the risk factors of development of t-MNs. A recent meta-analysis7 did not confirm an association between t-MNs and previously identified clinical risk factors, such as germline BRCA variants, prolonged exposure to certain chemotherapy agents, and recurrent disease.

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