Dr Asare on the Elevated Risk of Secondary Leukemias in PARP Inhibitors in Gynecologic Cancers

Amma Asare, MD, PhD, gynecologic oncology fellow, The University of Texas MD Anderson Cancer Center, discusses the risk of therapy-related myeloid neoplasms or secondary leukemias in patients with gynecologic cancers being treated with PARP inhibitors.

Although secondary cancers are a known risk following cancer treatment, recent data suggest that this risk is elevated in patients with gynecologic malignancies receiving PARP inhibitors compared with other therapies, Asare notes. In a study presented at the 2024 SGO Annual Meeting, Asare and colleagues found that the risk of secondary leukemia developing in patients with gynecologic cancers being treated with PARP inhibitors was approximately 9% compared with the approximate 1% risk for other therapies.

The study aimed to identify factors that could predict which patients may be at higher risk of developing secondary leukemia after treatment with PARP inhibitors. Asare highlightes three key categories of risk factors: time-related factors, chemotherapy-related factors, and patient-specific factors.

Asare explains that time-related factors included the duration from ovarian cancer diagnosis to the initiation of PARP inhibitor therapy. Patients who developed secondary leukemia tended to have a longer interval between diagnosis and the start of PARP inhibitor treatment, she says.

Chemotherapy-related factors were also significant, particularly the number of chemotherapy cycles. Patients who received a higher number of carboplatin cycles and overall chemotherapy cycles prior to PARP inhibitor therapy were more likely to develop secondary leukemia. This suggests that cumulative exposure to DNA-damaging agents may contribute to the elevated risk.

Lastly, Asare explains that germline mutations in BRCA1 were overrepresented among those who developed secondary leukemia, suggesting a potential interaction between inherited genetic risk and treatment exposure.

Asare concludes that these findings underscore the need for careful risk assessment when considering PARP inhibitors for patients with ovarian cancer. Identifying high-risk patients could guide treatment decisions and inform surveillance strategies to mitigate the risk of therapy-related secondary malignancies