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<p>Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML), but its significance in patients treated with azacitidine and venetoclax (AZA/VEN) outside clinical trials remains unclear. We retrospectively analyzed 220 newly diagnosed AML patients from the French VENAURA registry who achieved composite complete remission and underwent MRD evaluation by multiparametric flow cytometry (MFC, LAIP/LSC) and/or <i>NPM1</i> RT-qPCR. Cumulative MRD negativity was achieved in 62–67% of patients. Attaining MRD negativity at any time was strongly associated with superior overall survival (OS: 31.3 months vs 15.7 months (HR = 0.47) for LAIP, not reached vs 10.8 months (HR = 0.38) for <i>NPM1</i>; all <i>p</i> &lt; 0.001) and lower cumulative incidence of relapse. Dual LAIP/LSC negativity (NEG/NEG) conferred the best outcomes compared to NEG/POS (HR = 0.36, <i>p</i> = 0.02), POS/NEG (HR = 0.24, <i>p</i> &lt; 0.001) and POS/POS (HR = 0.26, <i>p</i> = 0.26) status. Importantly, MRD response mitigated the adverse prognostic impact of ELN 2024 intermediate/poor risk, with MRD-negative patients achieving outcomes comparable to favorable-risk cases. MRD kinetics (early vs late responders) did not affect survival, while G-CSF use improved MRD conversion and OS. In real-world AZA/VEN–treated AML, achieving deep MRD negativity, by MFC or <i>NPM1</i> RT-qPCR, emerges as the dominant prognostic determinant, overriding baseline risk and supporting its integration into response-adapted strategies.</p>

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Prognostic impact of measurable residual disease in AML patients treated frontline with azacitidine and venetoclax: results from the French VENAURA registry

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Maël Heiblig,
  • Zofia Gross,
  • Amine Belhabri,
  • Urbain Tauveron-Jalenques,
  • Emmanuelle Tavernier,
  • Gaspar Requena Aspas,
  • Martin Carré,
  • Adrien Contejean,
  • Nadine Boullanger Fow Heng,
  • Clémence Santana,
  • Clément Rocher,
  • Sylvain Lamure,
  • Gian-Matteo Pica,
  • Mauricette Michallet,
  • Jérôme Cornillon,
  • Mathieu Meunier,
  • Natacha Mauz,
  • Samy Chraibi,
  • Ugo Thevenet,
  • Arthur Dony,
  • Grégoire Le Meur,
  • Lucie Coster,
  • Sylvie Tondeur,
  • Emmanuel Beillard,
  • Serge Carillo,
  • Delphine Manzoni,
  • Pascale Flandrin,
  • Thomas Tassin,
  • Sarah Huet,
  • Adriana Plesa,
  • Guieze Romain,
  • Aspas Requena Gaspar,
  • Fayard Amandine,
  • Ravinet Aurélie,
  • Abdo Chrystelle,
  • Abitayeh Rami,
  • Balsat Marie,
  • Baroudi Nboureddine,
  • Barraco Fiorenza,
  • Beillard Emmanuel,
  • Belhabri Amine,
  • Cacheux Victoria,
  • Carre Martin,
  • Chevalier Simon,
  • Contejean Adrien,
  • Cornillon Jérome,
  • Dony Arthur,
  • Doublet Charlotte,
  • Ducastelle-Lepretre Sophie,
  • Duprat Manon,
  • Faure Anne Camille,
  • Flandrin-Gresta Pascale,
  • Fossard Gaelle,
  • Gilis Lila,
  • Girard Sandrine,
  • Grange Béatrice,
  • Hacini Maya,
  • Hayette Sandrine,
  • Huet Sarah,
  • Jacob Marie Christine,
  • Labussière-Wallet Hélène,
  • Lachenal Florence,
  • Lefebvre Christine,
  • Legrand Clémentin,
  • Lours Camille,
  • Loron Sandrine,
  • Manzoni Delphine,
  • Mauz Natacha,
  • Meunier Mathieu,
  • Michallet Mauricette,
  • Moluçon-Chabrot Cécile,
  • Virelizier Emmenuelle-Nicolas,
  • Noyel Pauline,
  • Park Sophie,
  • Parry Anne,
  • Raskovalova Tatiana,
  • Rigollet Lauren,
  • Rocher Clément,
  • Sujobert Pierre,
  • Santana Clémence,
  • Tardy Stéphanie,
  • Tavernier Emmanuelle,
  • Thiebaut Francoise,
  • Thiebaut-Bertrand Anne,
  • Tigaud Isabelle,
  • Tondeur Sylvie,
  • Gire Marion,
  • Joassard Anaelle,
  • Jaillard Lucie,
  • Coster Lucie,
  • Tauveron-Jalenques Urbain,
  • Grimaud Yoann,
  • Plesa Adriana,
  • Lamure Sylvain,
  • Fatrara Thomas

摘要

Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML), but its significance in patients treated with azacitidine and venetoclax (AZA/VEN) outside clinical trials remains unclear. We retrospectively analyzed 220 newly diagnosed AML patients from the French VENAURA registry who achieved composite complete remission and underwent MRD evaluation by multiparametric flow cytometry (MFC, LAIP/LSC) and/or NPM1 RT-qPCR. Cumulative MRD negativity was achieved in 62–67% of patients. Attaining MRD negativity at any time was strongly associated with superior overall survival (OS: 31.3 months vs 15.7 months (HR = 0.47) for LAIP, not reached vs 10.8 months (HR = 0.38) for NPM1; all p < 0.001) and lower cumulative incidence of relapse. Dual LAIP/LSC negativity (NEG/NEG) conferred the best outcomes compared to NEG/POS (HR = 0.36, p = 0.02), POS/NEG (HR = 0.24, p < 0.001) and POS/POS (HR = 0.26, p = 0.26) status. Importantly, MRD response mitigated the adverse prognostic impact of ELN 2024 intermediate/poor risk, with MRD-negative patients achieving outcomes comparable to favorable-risk cases. MRD kinetics (early vs late responders) did not affect survival, while G-CSF use improved MRD conversion and OS. In real-world AZA/VEN–treated AML, achieving deep MRD negativity, by MFC or NPM1 RT-qPCR, emerges as the dominant prognostic determinant, overriding baseline risk and supporting its integration into response-adapted strategies.