Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience.
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Marmouset Vincent, Decroocq Justine, Garciaz Sylvain, Etienne Gabriel, Belhabri Amine, Bertoli Sarah, Gastaud Lauris, Simand Célestine, Chantepie Sylvain, Uzunov Madalina, Genthon Alexis, Berthon Céline, Chiche Edmond, Dumas Pierre-Yves, Vargaftig Jacques, Salmeron Géraldine, Lemasle Emilie, Tavernier Emmanuelle, Delage Jérémy, Loirat Marion, Morineau Nadine, Blanc-Durand Félix, Pautier Patricia, Vergé Véronique, Auger Nathalie, Thomas Myrtille, Stefani Laetitia, Lepelley Marion, Boyer Thomas, Thepot Sylvain, Gourin Marie-Pierre, Bourquard Pascal, Duchmann Matthieu, Morice Pierre-Marie, Michallet Mauricette, Adès Lionel, Fenaux Pierre, Récher Christian, Dombret Hervé, Pagès Arnaud, Marzac Christophe, Leary Alexandra, Micol Jean-Baptiste, UNIHEM, French Network of Pharmacovigilance Centers, ALFA, FILO, and GFM
Аннотация
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.