Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown. Patients and Methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers. HAEs were manually identified by searching the patients’ electronic medical records and classified by CTCAE v5.0. The main endpoint was the incidence rate of any HAE (ie, anaemia, neutropenia, or thrombocytopenia) of grade 2 or more (G ≥ 2). Results: One hundred and sixty-six patients were included; 95 (57%) had a gBRCA-PV. In total, 162 incident cases of G ≥ 2 HAEs were reported over 255.3 person-years. The incidence rates of G ≥ 2 HAEs were 1003/1000 person-years in gBRCA-PV carriers and 993/1000 person- years in non-carriers. No difference in the incidence rate of G ≥ 2 HAEs emerged comparing gBRCA-PV carriers to non-carriers (crude- incidence rate ratio [IRR]: 1.01; 95% CI: 0.72, 1.43; P = .96), even after adjusting for the type of PARPi (Mantel-Haenszel IRR: 0.99; 95% CI: 0.67, 1.46). Conclusion: Patients with aHGOC and a gBRCA-PV do not experience higher PARPi-related HAEs compared to non-gBRCA-PV carriers, unlike platinum salt-related HAEs.