Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3-mutated AML: a phase 3b trial

The pivotal RATIFY study demonstrated midostaurin (50 mg twice daily) with standard chemotherapy significantly reduced mortality in adult patients (<60 years) with newly diagnosed (ND) FLT3(mut) acute myeloid leukemia (AML). Considering that AML often present in older patients who show poor response to chemotherapy, this open-label, multicenter phase 3b trial was designed to further assess safety and efficacy of midostaurin plus chemotherapy in induction, consolidation, and maintenance monotherapy in young (<= 60 years) and older (>60 years) patients with FLT3(mut) ND-AML. Compared with RATIFY, this study extended midostaurin treatment from 14 days to 21 days, substituted anthracyclines (idarubicin or daunorubicin), and introduced variation in standard combination chemotherapy dosing (7+3 or 5+2 in more fragile patients). Total 301 patients (47.2% >60 years and 82.7% with FLT3-ITDmut) of median age 59 years entered induction phase. Overall, 295 patients (98.0%) had at least 1 adverse event (AE), including 254 patients (84.4%) with grade >= 3 AE. The grade >= 3 serious AEs occurred in 134 patients. No difference was seen in AE frequency between age groups, but grade >= 3AE frequency was higher in older patients. Overall, complete remission (CR) rate including incomplete hematologic recovery (CR + CRi) (80.7% [95% confidence interval, 75.74-84.98]) was comparable between age groups (<= 60 years [83.5%]; >60 to <= 70 years [82.5%]; in patients >70 years [64.1%]) and the type of anthracycline used in induction. CR + CRi rate was lower in males (76.4%) than females (84.4%). Overall, the safety and efficacy of midostaurin remains consistent with previous findings, regardless of age, sex, or induction regimen. The trial is registered at www.clinicaltrials.gov as #NCT03379727.

Automated summary

The pivotal RATIFY study demonstrated that midostaurin combined with standard chemotherapy significantly reduced mortality in adult patients with newly diagnosed FLT3(mut) acute myeloid leukemia. This open-label, multicenter phase 3b trial aimed to further assess the safety and efficacy of midostaurin plus chemotherapy in different age groups. The results showed that the safety and efficacy of midostaurin remained consistent with previous findings regardless of age, sex, or induction regimen.