Prospective evaluation of gene mutations and minimal residual disease (MRD) in patients with core binding factor acute myeloid leukemia (CBF-AML)
Menée sur 188 patients atteints d'une leucémie myéloïde aiguë à "core binding factor" et inclus dans l'essai clinique français CBF-2006 (durée de suivi : 36 mois), cette étude suggère que l'évaluation de la maladie résiduelle minimale est plus efficace que le statut des mutations KIT ou FLT3 pour le pronostic de la maladie
Not all the patients with CBF-AML display a good outcome. Modern risk factors include KIT and/or FLT3 gene mutations and MRD levels, but their respective values have never been prospectively assessed. One hundred ninety-eight CBF-AML patients were treated in this French Intergroup CBF-2006 trial. They were randomized between a reinforced and a standard induction course, followed by three high-dose cytarabine consolidation courses. MRD levels were monitored prospectively. Gene mutations were screened at diagnosis. Despite a more rapid MRD decrease after reinforced induction, induction arm did not influence the outcome (relapse-free survival [RFS], 64% in both arms; P=0.91). Higher WBC, KIT and/or FLT3-ITD/TKD gene mutations, and a less than 3-log MRD reduction after the first consolidation course were associated with a higher specific hazard of relapse, but MRD response remained the sole significant prognostic factor in multivariate analysis. At 36 months, cumulative incidence of relapse and RFS were 22% versus 54% (P<0.001) and 73% versus 44% (P<0.001) in patients who achieved 3-log MRD reduction versus those who did not, respectively. These results strongly suggest that MRD response should be used in these patients, rather than KIT or FLT3 gene mutations, as a tool for future treatment stratifications. EudraCT number, 2006-005163-26 ClinicalTrials.gov ID, NCT 00428558
Blood , résumé, 2013