Recurrence after Long-Term Use of Poly ADP-Ribose Polymerase Inhibitors Triggered by Therapy-Related Myeloid...

Poly ADP-ribose polymerase (PARP) inhibitors are used as maintenance therapy for recurrent ovarian cancer, but their long-term safety, especially the risk of therapy-related myeloid neoplasms, remains a concern. Here, we report a case of disease recurrence and myeloid neoplasms following long-term treatment with PARP inhibitors.

A 49-year-old woman presented with stage IIIC (FIGO 2014), high-grade serous ovarian carcinoma. After initial surgery and chemotherapy, she achieved a complete response but experienced six recurrences between 2010 and 2017, each treated with chemotherapy. At the time of her sixth relapse, she received five cycles of nedaplatin and was subsequently administered olaparib. No notable adverse events occurred during olaparib treatment. Five years after starting olaparib treatment, she developed myelodysplastic syndrome, which progressed to acute myeloid leukemia after 2 months. Olaparib treatment was stopped following the diagnosis of myelodysplastic syndrome. She received eight cycles of venetoclax and azacitidine for approximately 1 year following her diagnosis of acute myeloid leukemia, but no hematologic response was achieved. Furthermore, she developed abnormal genital bleeding and recurrent ovarian cancer manifested as a rectovaginal fistula. Considering the seriousness of her condition, she was placed on best supportive care. She was eventually transferred to a hospice program, where she died from ovarian cancer and acute myeloid leukemia.

While long-term PARP inhibitor therapy may prolong survival in ovarian cancer, this case highlights the risk of therapy-related myeloid neoplasms, particularly in heavily pretreated patients, and underscores the need for careful long-term monitoring and consideration of optimal maintenance duration.