Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia patients treated in the ALFA0701 trial.
Fiche publication
Date publication
décembre 2019
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CAILLOT Denis
Tous les auteurs :
Fournier E, Duployez N, Ducourneau B, Raffoux E, Turlure P, Caillot D, Thomas X, Marceau-Renaut A, Chantepie SP, Malfuson JV, Lemasle E, Cheok MH, Celli-Lebras K, Guerin E, Terré C, Lambert J, Pautas C, Dombret H, Castaigne S, Preudhomme C, Boissel N
Lien Pubmed
Résumé
Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by miscellaneous genetic background and response to chemotherapy. While molecular aberrations are routinely used to stratify AML patients into prognostic subgroups when receiving standard chemotherapy, the predictive value of the genetic background and co-occurring mutations remains to be assessed when using newly approved anti-leukemic drugs. Here, we report the mutational landscape of patients aged 50 to 70 years old with non-CBF AML and treated in the ALFA-0701 study. We retrospectively addressed the question of the predictive value of molecular events on the benefit of the addition of gemtuzumab ozogamicin (GO) to standard front-line chemotherapy. Using here the more recent ELN 2017 risk classification, we confirmed that the benefit of GO was restricted to the favorable (HR 0.54, 95%CI[0.30-0.98]) and intermediate (HR 0.57; 95%CI[0.33-1.00]) risk categories whereas it did not influence outcome of patients within the adverse risk subgroup (HR 0.93, 95%CI[0.61-1.43]). Interestingly, the benefit of GO was significant for patients with activating signaling mutations (HR 0.43, 95%CI[0.28-0.65]) which correlated to higher CD33 expression levels. These results suggest that molecular aberrations could be critical for future differentially tailored treatments based on integrated genetic profiles able to predict the benefit of GO on outcome.
Référence
Blood. 2019 Dec 27;: