Incidence, characteristics and outcome of therapy-related myeloid neoplasms in women with epithelial ovarian cancer after exposure to poly-ADPribose polymerase inhibitors: A cancer center experience

Abstract

Poly(ADP-ribose) polymerase inhibitors (PARPi) target the DNA repair pathways and have been established in epithelial ovarian cancer (EOC) as maintenance therapy inducing prolonged survival. However, recently published data showed that PARPi may increase the risk of therapy-related myeloid neoplasms (t-MN) including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Herein, we investigated the incidence, characteristics, and management of t-MN among EOC patients after exposure to PARPi in a Greek Cancer Center. We analyzed 112 consecutive EOC patients treated with PARPi with a median age of 58 years (range 28-84). Olaparib and Niraparib were used in 90 and 22 patients, respectively. The median number of previous chemotherapy lines and duration of treatment with PARPi were 2 (range 1-9) lines and 12 (range 2-24) months, respectively. The incidence of t-MN among patients treated with PARPi was 3.57% (4/112). Patients with t-MN were distributed as follows: t-MDS: 1, t-MDS/AML: 1, t-AML: 2. We observed adverse cytogenetic features in t-MN patients leading to dismal prognosis. In conclusion, in accordance with previous real-world reports, we confirm a notable risk for t-MN in EOC patients treated with PARPi. As PARPi are an emerging therapy for many neoplasms, there is an unmet clinical need to identify patients who are considered at high risk for developing t-MN post-therapy with PARPi in order to introduce potential preventive strategies.

Keywords: ovarian cancer; poly(ADP‐ribose) polymerase inhibitors (PARPi); therapy‐related myeloid neoplasms.