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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; [...]

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

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  • Media type: E-Article
  • Title: Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
  • Contributor: 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; [...]
  • Published: American Association for Cancer Research (AACR), 2022
  • Published in: Clinical Cancer Research, 28 (2022) 23, Seite 5211-5220
  • Language: English
  • DOI: 10.1158/1078-0432.ccr-22-1622
  • ISSN: 1078-0432; 1557-3265
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access