Therapy Related Myeloid Neoplasms Following PARP Inhibitors: Real-Life Experience.

Vincent Marmouset (1) , Justine Decroocq , Sylvain Garciaz (2) , Gabriel Etienne , Amine Belhabri , Sarah Bertoli , Lauris Gastaud , Célestine Simand , Sylvain Chantepie , Madalina Uzunov , Alexis Genthon , Céline Berthon , Edmond Chiche , Pierre-Yves Dumas , Jacques Vargaftig , Géraldine Salmeron , Emilie Lemasle , Emmanuelle Tavernier , Jérémy Delage , Marion Loirat , Nadine Morineau , Félix Blanc-Durand (3, 4) , Patricia Pautier (3, 4) , Véronique Vergé , Nathalie Auger , Myrtille Thomas , Laetitia Stefani , Marion Lepelley , Thomas Boyer (5, 6) , Sylvain Thepot , Marie-Pierre Gourin , Pascal Bourquard , Matthieu Duchmann (7) , Pierre-Marie Morice , Mauricette Michallet , Lionel Adès , Pierre Fenaux , Christian Récher , Hervé Dombret (8) , Arnaud Pagès (9) , Christophe Marzac , Alexandra Leary (3) , Jean-Baptiste Micol (10)

1 Département d'hématologie [Gustave Roussy]
2 CRCM - Centre de Recherche en Cancérologie de Marseille
3 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
4 Département de médecine oncologique [Gustave Roussy]
5 CHU Amiens-Picardie
6 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
7 GenCellDis (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
8 URP_3518 - Recherche clinique appliquée à l'hématologie
9 U1018 (Équipe 3) - Épidémiologie des radiations, épidémiologie clinique des cancers et survie
10 CSHMyelo - U1287 Inserm - Cellules souches hématopoïétiques et développement des hémopathies myéloïdes

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 ovarian cancer (OC) patients referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post PARPi among 37 t-MN post OC 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 OC patients treated with PARPi. At time of hematological consultation, patients with t-MN had a longer PARPi exposure (9 months vs. 3, p= 0.01), lower platelet count (74 vs. 173 G/L, p=0.0005), and more cytopenias (2 vs. 1, p=0.0005). Compared to t-MN not exposed to PARPi, t-MN-PARPi patients had more BRCA1/2 germline mutation (61.5% vs. 0% p=0.03) but similar 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 (IQR, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR 1.046, p=0.02), olaparib compared to others PARPi (HR 5.82, p=0.003) and AML (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.

Domaines: Médecine humaine et pathologie

Vincent Marmouset, Justine Decroocq, Sylvain Garciaz, Gabriel Etienne, Amine Belhabri, et al.. Therapy Related Myeloid Neoplasms Following PARP Inhibitors: Real-Life Experience.. Clinical Cancer Research, 2022, pp.CCR-22-1622. ⟨10.1158/1078-0432.CCR-22-1622⟩. ⟨hal-03814212⟩