Midostaurin plus intensive chemotherapy for younger and older Patients with AML and FLT3 internal tandem duplications

We conducted a single-arm phase-II trial (AMLSG 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a one-year midostaurin maintenance therapy in adult patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (ITD). Patients 18-70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free (EFS) and overall survival (OS). Results were compared to a historical cohort of 415 patients treated on 5 prior AMLSG trials; statistical analysis was performed using a double-robust adjustment with propensity score weighting and covariate adjustment. Results were also compared to patients (18-59yrs) treated on the placebo arm of the CALGB 10603/RATIFY trial. The trial accrued 440 patients (18-60yrs, n=312; 61-70yrs, n=128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared to the AMLSG control (HR 0.55; P