Event-free survival improved with midostaurin for patients with FLT3-ITD-mutated AML

The addition of the multi-targeted kinase inhibitor, midostaurin, to chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) significantly improved event-free survival (EFS) for patients with acute myeloid leukemia (AML) with FLT3 internal tandem duplication (ITD). That’s according to the results of a phase-2 trial that included 284 patients who were 18-70 years old with newly diagnosed AML with FLT3-ITD.

Of patients treated, 76.4% obtained complete remission (CR) or CR with incomplete hematological recovery (CRi) after induction therapy. The majority of patients in CR/CRi (72.4%) underwent HCT. 

The study group results were compared to a historical control cohort with 415 patients who received idarubicin, cytarabine and etoposide induction therapy. In this cohort, 286 patients achieved CR/CRi (68.9%) after induction therapy and 42.8% (n=122) proceeded to allogeneic HCT in first CR/CRi. Overall, 57.1% (n=237) of patients in the control cohort received allogeneic HCT. (See chart below.)

  N Age subgroups CR/CRi (%) Allo-HCT (%) 2-year EFS (%)    
Midostaurin protocol  











Control group





  68.9   overall      57 overall




With the midostaurin protocol, EFS and overall survival at two years were 39% (95% confidence interval [CI], 33-47%) and 34% (95% CI, 24-47%) for younger patients; and 53% (95% CI, 46-61%) and 46% (95% CI, 35-59%) for older patients. In comparison to the control group, a propensity score-weighted analysis showed a substantial EFS improvement with midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70, p<0.001) across both younger and older age groups. Researchers ruled out that improvements in EFS were influenced by higher transplant rates in the mitostaurin cohort. 

Patients who received midostaurin during maintenance experienced additional toxicity with immunosuppressants and anti-infectives. However, the landmark analysis 100 days after HCT favored post-HCT maintenance with better EFS and OS for patients starting within 100 days after transplant.  

The researchers concluded that adding midostaurin to induction and maintenance therapy improved EFS in young and older patients with FLT3-ITD-mutated AML.

Schlenk RF, et al., Blood Journal