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

Abstract

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.

• Authors: Vincent Marmouset, Justine Decroocq, Sylvain Garciaz, 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, Patricia Pautier, Véronique Vergé, Nathalie Auger, Myrtille Thomas, Laetitia Stefani, Marion Lepelley, Thomas Boyer, Sylvain Thepot, Marie-Pierre Gourin, Pascal Bourquard, Matthieu Duchmann, Pierre-Marie Morice, Mauricette Michallet, Lionel Adès, Pierre Fenaux, Christian Récher, Hervé Dombret, Arnaud Pagès, Christophe Marzac, Alexandra Leary, Jean-Baptiste Micol, UNIHEM, French Network of Pharmacovigilance Centers, ALFA, FILO, and GFM
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 23 Pg. 5211-5220 (12 01 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 36201165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Poly(ADP-ribose) Polymerase Inhibitors

Topics

• Female
• Humans
• Poly(ADP-ribose) Polymerase Inhibitors (adverse effects)
• Ovarian Neoplasms (drug therapy, genetics)
• Carcinoma, Ovarian Epithelial
• Mutation
• Germ-Line Mutation
• Neoplasms, Second Primary (diagnosis, epidemiology)