Prognostic Impact of
FLT3
‐
ITD
Allelic Ratio in
AML
Mathieu Leclerc, Etienne Audureau, Nicolas Duployez, Mathilde Hunault, Emmanuelle Tavernier, Cécile Pautas, Sarah Bertoli, Emmanuel Raffoux, Marie‐Anne Hospital, Tony Marchand, Maël Heiblig, Sylvain Chantepie, Martin Carre, Pierre Peterlin, Maria‐Pilar Gallego‐Hernanz, Romain Guieze, Célestine Simand, Pascal Turlure, Anne Huynh, Emilie Lemasle, Ludovic Gabellier, Juliette Lambert, Felipe Suarez, Samy Chraibi, Laurence Sanhes, Karine Celli‐Lebras, Ariane Mineur, Claude Gardin, Jean‐Valère Malfuson, Thomas Cluzeau, Norbert Vey, Régis Peffault de Latour, Lucie Rigolot, Isabelle Luquet, Dominique Penther, Raphael Itzykson, Eric Delabesse, Jean‐François Hamel, Stéphane de Botton, Arnaud Pigneux, Hervé Dombret, Claude Preudhomme, Christian Recher, Pierre‐Yves Dumas ABSTRACT
The prognostic value of FLT3 internal tandem duplication ( FLT3 ‐ITD) in acute myeloid leukemia (AML) has traditionally been stratified according to the ITD/wild‐type allelic ratio (AR) and NPM1 co‐mutation status. We evaluated the prognostic impact of FLT3 ‐ITD AR in 459 newly diagnosed AML patients younger than 60 years enrolled in the prospective BIG‐1 study, all treated with high‐dose anthracycline‐based induction. From 2018 onward, midostaurin was added for FLT3 ‐mutated cases. AR was not associated with composite complete remission (81.7% vs. 79.6% in low vs. high AR, p = 0.85), overall survival (OS) (median 7.6 vs. 6.9 years, p = 0.25), relapse‐free survival (median 2.0 vs. 1.7 years, p = 0.50), or event‐free survival (median 1.4 vs. 1.2 years, p = 0.58). In multivariable analyses, only midostaurin exposure (adjusted hazard ratio [aHR] 0.69, 95% CI 0.50–0.95, p = 0.024) and adverse ELN‐2022 risk (aHR 1.66, 95% CI 1.18–2.34, p = 0.004) were independently associated with OS. Allogeneic hematopoietic stem cell transplantation was associated with improved relapse‐free (aHR 0.40, 95% CI 0.29–0.55, p < 0.001) and event‐free survival (aHR 0.37, 95% CI 0.27–0.51, p < 0.001), but not OS. These results indicate that FLT3 ‐ITD AR has no independent prognostic impact in younger AML patients treated with intensive anthracycline‐based chemotherapy and midostaurin in contemporary clinical practice.