Real-world incidence and risk of myelodysplastic syndrome and acute myeloid leukemia secondary to PARP inhibitors in ovarian cancer.

purposeTo analyze the association between myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and PARP inhibitors (PARPi), to explore predisposing factors, and to evaluate their effectiveness and safety in clinical practice.

methodsObservational, analytical and retrospective study including patients with ovarian cancer treated with olaparib or niraparib from 2014 to 2024. Primary endpoint was to identify the incidence and risk factors of secondary malignancy, considering treatment duration, BRCA mutation, lines of platinum-based chemotherapy and grade 3-4 adverse events (AEs). Overall survival (OS), progression-free survival (PFS), and AEs were recorded.

resultsEighty patients were included. Six developed secondary MDS/AML, with an incidence of 11.6% (5/43) for olaparib and 2.7% (1/37) for niraparib. No significant correlation was found, except for hematological grade 3-4 AEs, associated with a higher risk of developing MDS/AML (OR: 32.3 p = 0.001). The median latency period was 8.8 months (1.5-102.2). For olaparib, median PFS was 37.8 months (95% CI 17.0-58.6); OS was not reached. For niraparib PFS was 10.0 months (95% CI 7.4-12.5), OS 25.1 months (95% CI 6.3-43.9). Grade 3-4 AEs occurred in 32.6% of olaparib and 35.2% of niraparib patients, mainly anemia and thrombocytopenia.

conclusionsPARPi are effective and generally with a manageable safety profile. However, secondary MDS and AML, though rare, remain serious adverse events with incompletely defined risk factors. The observed incidence, particularly with olaparib, is comparable to or higher than that reported in trials, though the sample size was limited. Close monitoring of hematologic AEs may be key to preventing these neoplasms.