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<p>Measurable residual disease (MRD) is a major prognostic factor in Core Binding Factor (CBF) AML. <i>KIT</i> or <i>FLT3</i> mutations also have prognostic relevance, but little is known about their prognostic value when accounting for MRD. We analyzed the prognostic value of genetic alterations adjusting for early MRD response in adult CBF-AML patients. We grouped data from the retrospective multicenter study RetroCBF (NCT05070208, training set) and the prospective CBF-2006 trial (NCT00428558, validation set). Centralized high-throughput sequencing was performed with 36 genes. 656 CBF-AML patients in first CR were included between 2007 and 2020 (RetroCBF <i>n</i> = 461; CBF-2006 <i>n</i> = 195). In a LASSO-penalized model including MRD and genetic alterations performed in the RetroCBF training cohort, <i>KIT</i>-TKD in <i>RUNX1::RUNX1T1</i> and <i>FLT3</i>-ITD in <i>CBFB::MYH11</i> were associated with a higher risk of relapse. Including these genetic alterations with MRD in the training cohort, 3-year cumulative incidence of relapse was 22% (95%CI:13–33%) in low-risk patients (MRD low AND no <i>KIT</i>-TKD [<i>RUNX1::RUNX1T1</i>] or <i>FLT3</i>-ITD [<i>CBFB::MYH11</i>]) versus 53% (95%CI 46%-60%) in high-risk patients (csHR=3.21 [95%CI:1.83–5.62], <i>p</i> &lt; 0.0001). These results were confirmed in the CBF-2006 validation cohort. <i>KIT</i>-TKD mutations in <i>RUNX1::RUNX1T1</i> and <i>FLT3</i>-ITD in <i>CBFB::MYH11</i> worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.</p>

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Genetic alterations and measurable residual disease in core binding factor acute myeloid leukemia

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Loïc Vasseur,
  • Matthieu Duchmann,
  • Nicolas Duployez,
  • Emmanuel Raffoux,
  • Céline Berthon,
  • Maël Heiblig,
  • Alexis Genthon,
  • Thorsten Braun,
  • Mathieu Leclerc,
  • Delphine Lebon,
  • Sylvain Chantepie,
  • Jean-Baptiste Micol,
  • Juliette Lambert,
  • Christian Récher,
  • Marie-Lorraine Chrétien,
  • Alexandre Iat,
  • Julien Vaidie,
  • Jean-Valère Malfuson,
  • Madalina Uzunov,
  • Arnaud Pigneux,
  • Pierre Peterlin,
  • Sihem Tarfi,
  • Pierre Hirsch,
  • Dominique Penther,
  • Eric Jourdan,
  • Karine Celli-Lebras,
  • Claude Preudhomme,
  • Hervé Dombret,
  • Jérôme Lambert,
  • Nicolas Boissel,
  • Raphaël Itzykson

摘要

Measurable residual disease (MRD) is a major prognostic factor in Core Binding Factor (CBF) AML. KIT or FLT3 mutations also have prognostic relevance, but little is known about their prognostic value when accounting for MRD. We analyzed the prognostic value of genetic alterations adjusting for early MRD response in adult CBF-AML patients. We grouped data from the retrospective multicenter study RetroCBF (NCT05070208, training set) and the prospective CBF-2006 trial (NCT00428558, validation set). Centralized high-throughput sequencing was performed with 36 genes. 656 CBF-AML patients in first CR were included between 2007 and 2020 (RetroCBF n = 461; CBF-2006 n = 195). In a LASSO-penalized model including MRD and genetic alterations performed in the RetroCBF training cohort, KIT-TKD in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 were associated with a higher risk of relapse. Including these genetic alterations with MRD in the training cohort, 3-year cumulative incidence of relapse was 22% (95%CI:13–33%) in low-risk patients (MRD low AND no KIT-TKD [RUNX1::RUNX1T1] or FLT3-ITD [CBFB::MYH11]) versus 53% (95%CI 46%-60%) in high-risk patients (csHR=3.21 [95%CI:1.83–5.62], p < 0.0001). These results were confirmed in the CBF-2006 validation cohort. KIT-TKD mutations in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.