P523: Midostaurin Plus Intensive Chemotherapy in Flt3 Mutated Aml. “Real Life” Data Versus the Ratify Study

Abstract

Background: Background: FLT3 mutation is associated with adverse prognosis in AML (ELN2017, Dohner et al, Blood 2017) and Intensive chemotherapy (IC) has been the standard of treatment for FLT3 mutated AML for decades. Midostaurin (Midos) has been approved in combination with IC for FLT3-mutated AML based on an improvement in overall survival noted in the RATIFY phase 3 trial (Stone et al, N Engl J Med 2017) Aims: Aims: The aims of this study are to analyze safety and effectiveness of Midos plus IC in FLT3 AML, to validate RATIFY results in a "real-world" setting and to identify risk factors. Methods: Methods: We carried out a retrospective multicenter study (MDA-AML-2018-06) in 27 Spanish centers. Inclusion criteria: age >18 years, FLT3-mutated AML diagnosis according to WHO criteria and start of treatment with midostaurin in combination with IC between June 2016 and June 2021. We evaluated the response according to 2017 ELN criteria, toxicity according to CTCAE v4.0 and overall survival (OS) by Kaplan-Meier. Statistical analysis was performed using SPSS program version 20.0. Results:Results: A total of 175patients (pt) were included (93 female), median age 53 (18-76), of them 111were younger than 60yrs and 110pts had ECOG<2. ELN2017 stratification was favorable in 53pt; Intermediate: 72pt; adverse in 26pt. Median WBC count 44.500/µL (0.4-395.000). A total of 133pts had FLF3-ITD mutation and of them 74pt with ratio ≥0.5. Safety: Total Midos cycles 548 (median 2), 20 pt (11.5%) suffered QT prolongation, 26pt (14,8%) Midos interruption and 10pt (5.7%) Midos reduction. There were no deaths related to Midos. Effectiveness: 144 (81.4%) pt achieved CR after Induction1or2, of them 76pt were consolidated with alloSCT, 24pt received maintenance and 41pt proceed to W&W. Median OS for the whole population was not reached and the 24months OS was 68%. In our experience ELN2917 classification and ECOG<2 identify groups with differences in OS (p0.019 and p0.04 respectively). Age <60vs≥60 resulted in no differences for OS. We observed significant differences for maintenance versus W&W (p=0.001) in favorable and intermediate risk patients. Comparing maintenance vs alloSCT we observe no differences in the Intermediate ELN2017 group.