*3.2.5 Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)*

MDS/AML occurred in patients treated with PARPi with incidences ranging from 0.2%1.7% in ovarian cancer clinical trials setting and some cases were fatal [21, 44, 47, 48, 51, 54, 55]. In a pharmacovigilance analysis of the FDA Adverse Events Reporting System (FAERS) database, a total of 319 cases of PARPi-associated MDS/ AML were identified from the period of quarter (Q)4, 2014 to Q1, 2020. Death or other life-threatening outcomes were reported in 49% of cases [67]. The duration of PARPi treatment varied from 1 month to >10 years. In all cases, patients had received previous platinum-based chemotherapy and/or other DNA damaging agents including radiation [21, 44, 47, 48, 51, 54, 55].

The mechanism of PARPi associated with MDS/AML remains unclear [67]. It is recommended to not start PARPi therapy until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ grade 1). For prolonged hematologic toxicities >4 weeks, patient shall be referred to a hematologist for further evaluation. If MDS/AML is confirmed, discontinue PARPi permanently [21, 44, 47, 48, 51, 55].
