Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience.

Autor:	Marmouset V; Department of Hematology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; Interception Program, Personalized Cancer Prevention Center, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Decroocq J; Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Service d'Hématologie Clinique, Hôpital Cochin, Paris, France., Garciaz S; Institut Paoli Calmettes, Marseille, France.; Cancer Research Center of Marseille, INSERM U1068, Aix-Marseille University, Marseille, France., Etienne G; Service d'hematologie, Institut Bergonie, Bordeaux, France., Belhabri A; Department of Oncology, Centre Leon Berard, Lyon, France., Bertoli S; Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université Toulouse III Paul Sabatier, Toulouse, France., Gastaud L; Hématologie, Center Antoine Lacassagne, Nice, France., Simand C; Department of Hematology, Institute for Cancer Strasbourg-Europe (ICANS), Strasbourg University, Strasbourg, France., Chantepie S; Department of Clinical Hematology, Caen University Hospital, Caen, France., Uzunov M; Service d'hématologie adulte, Hôpital Pitié-Salpêtrière, Paris, France., Genthon A; Department of Clinical Hematology, Saint Antoine Hospital, Sorbonne University, INSERM UMR-S 938, Paris, France., Berthon C; Department of Hematology, CHU Lille, Lille, France.; University of Lille, CNRS, Inserm, CHU Lille, IRCL, UMR9020 - UMR1277 - Canther - Cancer heterogeneity, plasticity and resistance to therapies, Lille, France., Chiche E; CHI Fréjus-St Raphael, Fréjus, France., Dumas PY; CHU Bordeaux, Service d'Hématologie Clinique et de Thérapie Cellulaire, Bordeaux, France., Vargaftig J; Division of Hematology, Curie Institute, Saint-Cloud, France., Salmeron G; Hématologie-oncologie, CHI Poissy-Saint-Germain-en-Laye, Poissy, France., Lemasle E; Département d'hématologie, Hôpital Henri Becquerel, Rouen, France., Tavernier E; Hématologie, Institut de Cancérologie-Hématologie Universitaire de Saint Etienne, France., Delage J; Département d'hématologie clinique, Saint Eloi, Montpellier, France., Loirat M; Service d'hématologie, Hôpital Saint Nazaire, Saint-Nazaire, France., Morineau N; Service d'hématologie, CHD de la Roche sur Yon, France., Blanc-Durand F; Department of Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; INSERM U981, Villejuif, France.; Interception Program, Personalized Cancer Prevention Center, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Pautier P; Department of Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; INSERM U981, Villejuif, France.; Interception Program, Personalized Cancer Prevention Center, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Vergé V; Department of Biology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Auger N; Department of Biology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Thomas M; Service Hématologie, CHU Clermont-Ferrand, France., Stefani L; Center Hospitalier Annecy Genevois, France., Lepelley M; Centre Régional de Pharmacovigilance - Addictovigilance, CHU de Grenoble-Alpes, France., Boyer T; Laboratoire d'Hématologie, Centre Hospitalier Universitaire d'Amiens, Amiens, France., Thepot S; Maladies du sang, CHU Angers, France., Gourin MP; Hématologie Clinique et Thérapie Cellulaire, CHU DUPUYTREN, Limoges, France., Bourquard P; Hématologie, CH ALES CEVENNES, France., Duchmann M; Université de Paris, Génomes, Biologie Cellulaire et Thérapeutique Unité (U)944, INSERM, Centre National de la Recherche Scientifique (CNRS), Paris, France., Morice PM; Department of Clinical Hematology, Caen University Hospital, Caen, France.; UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancer Prevention and Treatment), Normandie University, Caen, France., Michallet M; Department of Oncology, Centre Leon Berard, Lyon, France., Adès L; Hématologie Sénior Hôpital Saint Louis, Assistance publique hôpitaux de paris, and Université de Paris Cité, Paris, France., Fenaux P; Hématologie Sénior Hôpital Saint Louis, Assistance publique hôpitaux de paris, and Université de Paris Cité, Paris, France., Récher C; Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université Toulouse III Paul Sabatier, Toulouse, France., Dombret H; Adult Hematology Department, Saint-Louis Hospital, APHP, URP3518, Institut de Recherche Saint-Louis, Université de Paris, Paris, France., Pagès A; Bureau de Biostatistique et d'Épidémiologie - Gustave Roussy Équipe Oncostat - CESP U1018 - Inserm, France., Marzac C; Department of Biology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Leary A; Department of Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; INSERM U981, Villejuif, France.; Interception Program, Personalized Cancer Prevention Center, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Micol JB; Department of Hematology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; Interception Program, Personalized Cancer Prevention Center, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; INSERM U1287, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Dec 01; Vol. 28 (23), pp. 5211-5220.
DOI:	10.1158/1078-0432.CCR-22-1622
Abstrakt:	Purpose: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). Experimental Design: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. Results: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. Conclusions: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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