Germline BRCA pathogenic variants in patients with ovarian cancer and post-poly (ADP-ribose) polymerase inhibitor myeloid neoplasms.

Autor:	Valenza C; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Mongillo M; Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan., Gigli F; Division of Haematology Oncology, European Institute of Oncology, IRCCS, Milan., Trapani D; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Katrini J; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Nicolò E; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Boldrini L; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Boscolo Bielo L; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Castellano G; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Guidi L; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Pellizzari G; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Derio S; Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan., Lapresa M; Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan., Parma G; Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan., Derenzini E; Division of Haematology Oncology, European Institute of Oncology, IRCCS, Milan., Curigliano G; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan., Colombo N; Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan; Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Electronic address: nicoletta.colombo@ieo.it.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Sep; Vol. 9 (9), pp. 103685. Date of Electronic Publication: 2024 Aug 29.
DOI:	10.1016/j.esmoop.2024.103685
Abstrakt:	Background: Among patients with advanced high-grade ovarian carcinoma (aHGOC) treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), the presence of a germline BRCA pathogenic variant (gBRCA-PV) may increase the risk of bone marrow mutagenesis resulting in postcytotoxic therapy myelodysplastic neoplasms (MDS-pCT) or acute myeloid leukemia (AML-pCT), as it is expressed in heterozygosity also by hematopoietic progenitors. We aimed to investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to gBRCA-PV status. Patients and Methods: We conducted a retrospective single-center study to evaluate MDS/AML-pCT in patients with aHGOC and a known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi, in any line of therapy, from February 2017 to December 2022. The endpoint was the proportion of patients who experienced MDSs-pCT and AMLs-pCT during and after treatment with PARPi, in gBRCA-PV carriers and non-carriers. Results: A total of 166 patients were included: 95 (57%) had a gBRCA-PV and 72% received PARPi for recurrent disease. The number of lines of chemotherapies before and after PARPi, median overall survival, and median follow-up were comparable between gBRCA-PV carriers and non-carriers. After a median follow-up of 40.0 (95% confidence interval: 35.7-44.3) months, 10 (6%) patients were diagnosed with an MDS-pCT and 4 (2%) with an AML-pCT. A higher proportion of MDSs/AMLs-pCT (10% versus 2%; P = 0.16) and, in particular, of MDSs-pCT (9% versus 1%; P = 0.04) was observed among gBRCA-PV carriers. Conclusions: The presence of a gBRCA-PV is associated with a higher risk of MDS-pCT and possibly of myeloid neoplasms after PARPi in patients with aHGOC who received PARPi, especially in the setting of recurrent disease. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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