In:
European Journal of Haematology, Wiley, Vol. 107, No. 1 ( 2021-07), p. 111-121
Abstract:
In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m 2 of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate‐risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event‐free survival nor overall survival were improved by GO in younger AML patients ( 〈 60 years) ineligible for allogeneic stem‐cell transplantation. ( P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes ( NPM1 , FLT3 ‐ITD, CEBPA , DNMT3A , IDH1 , IDH2 , and ASXL1 ), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3 ‐ITD, NPM1 , and CEBPA mutations as well as epigenetic modifiers ( DNMT3A , IDH1/2 , ASXL1 ), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3 ‐ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients 〈 60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate‐risk cytogenetic.
Type of Medium:
Online Resource
ISSN:
0902-4441
,
1600-0609
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2027114-1
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