Therapy-related myeloid neoplasms in Korean patients with ovarian or primary peritoneal cancer treated with poly(ADP-ribose) polymerase inhibitors.

Abstract

Background: Prior prospective studies have demonstrated the efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPis) in various cancers with mutations in the breast cancer gene (BRCA), such as ovarian and breast cancers. However, PARPi have also been associated with an increased incidence of therapy-related myeloid neoplasms (t-MNs). This study aimed to investigate the incidence of t-MNs following PARPi therapy in patients with ovarian or primary peritoneal cancer in Korea and to identify related risk factors.

Methods: We retrospectively analyzed data of patients with ovarian or primary peritoneal cancer who received PARPi therapy between January 2015 and June 2023.

Results: Among 52 patients treated with PARPi, four were diagnosed with t-MNs. All four patients had BRCA mutations, and two of them had breast cancer with no evidence of disease (NED) status following treatment. All patients received radiotherapy and at least one granulocyte-colony stimulating factor (G-CSF) application. The median duration of PARPi therapy was 16.3 (range, 6.2-48.8) months. At the time of analysis, three patients had metastatic ovarian cancer and one maintained the NED status. Next-generation sequencing (NGS) performed in four patients revealed TP53 mutations and complex karyotypes in all tested patients. Among the four patients, three received only supportive care, and one was actively undergoing t-MN treatment.

Conclusions: The incidence of t-MNs after PARPi therapy in the current study was higher than that of overall t-MNs, which is consistent with the results of previous studies on t-MNs after PARPi therapy. Further international studies are needed to elucidate the mechanism and clinical characteristics of t-MNs associated with PARPi therapy.