Recurrence after Long-Term Use of Poly ADP‐Ribose Polymerase Inhibitors Triggered by Therapy-Related Myeloid Neoplasms: A Case Report

Abstract Background: Poly ADP-ribose polymerase inhibitors are used as maintenance therapy for recurrent ovarian cancer. Long-term use for relapsed patients who respond to treatment is acceptable; however, risks other than relapse have not been thoroughly examined. There has been growing concern that the use of poly ADP-ribose polymerase inhibitors in ovarian cancer patients, particularly those with recurrent disease, may be associated with an increased risk of therapy-related myeloid neoplasms. Here, we evaluated a case of disease recurrence and myeloid neoplasms following long-term treatment with poly ADP-ribose polymerase inhibitors. Case presentation: A 49-year-old woman presented with stage ⅢC (FIGO2014), high-grade serous ovarian carcinoma. In 2008, she underwent surgery and chemotherapy as initial treatment and achieved a complete response. Subsequently, she relapsed six times between 2010 to 2017 and underwent chemotherapy each time, which included paclitaxel, carboplatin, irinotecan, cisplatin, liposomal doxorubicin, docetaxel, and nedaplatin. At the time of her sixth relapse, her platinum-free interval was nine months, which is consistent with platinum-sensitive disease. 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 two months. Olaparib treatment was stopped following the diagnosis of myelodysplastic syndrome. She underwent chemotherapy (eight cycles of venetoclax and azacitidine) for approximately one year following her diagnosis of acute myeloid leukemia, but showed no improvement. Furthermore, she developed abnormal genital bleeding and recurrent ovarian cancer manifested as a rectovaginal fistula. Although her ovarian cancer stopped progressing with olaparib treatment, she developed therapy-related myeloid neoplasms. 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. Conclusions: Although poly ADP-ribose polymerase inhibitor treatment may promote long-term ovarian cancer survival, it may also increase the risk of fatal side effects, such as therapy-related myeloid neoplasms. For cases in which poly ADP-ribose polymerase inhibitors show sustained efficacy over a long period, it is important to consider the possibility that tumor cells have not been completely eradicated.