Research Summary

FLT3 Inhibitor Plus Chemotherapy Improves Survival in Patients with FLT3-mutated Acute Myeloid Leukemia

Anthony Calabro, MA

In a recent prospective study, researchers found that patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) treated with midostaurin plus intensive chemotherapy had improved 2-year overall survival (OS) when compared with chemotherapy alone.

With an incidence close to 30% for adults with AML, FLT3 is one of the most frequently mutated genes and often leads to a poor prognosis due to several factors including the allelic ratio of the mutation, the presence of comutations like NPM1, or the site of insertion. Post-remission, allogeneic hematopoietic cell transplantation (alloHCT) remains the recommended treatment option for this patient population.

But how patients with AML are treated is rapidly evolving due to several therapy developments including advances in targeted therapy, risk-adapted protocols, and the use of FLT3 inhibitors, such as midostaurin.

In the current study, researchers investigated the impact of midostaurin in 227 adult patients (aged 18 to 70 years) with FLT3-mutated AML. Patients were divided into early (2012-2015; n = 94) and late (2016-2020; n = 133) cohorts and were uniformly treated except for the addition of midostaurin in 71% of late group patients (n = 94).

Researchers found that the 2-year relapse incidence decreased from 42% in the early group to 29% in the late group (p = 0.024), and 2-year OS improved from 47% in the early group to 61% in the late group (p = 0.042). Midostaurin positively affected patients with NPM1 and FLT3 comutations as well. Of the 151 patients with NPM1 comutations, 2-year OS was 72% for the exposed group vs 50% for the naïve group (p = 0.011).

This study does have limitations. For example, the researchers retrospectively compared two different study periods. The researchers noted that the “favorable outcome of the late cohort might be influenced by other factors such as changes in alloHCT platforms or advances in support measures.”

Still, the researchers believe their results are notable.

“This study highlights the positive change in prognosis of patients with FLT3 mutations due to the association of chemotherapy and targeted therapy with midostaurin, in patients included in a prospective trial during 9 years comprising patients with an age up to 70 years and with a risk-adapted pre-defined post-remission alloHCT policy,” the authors concluded. “Further research is needed in patients with AML and FLT3 mutations in the absence of NPM1 mutation. It will also be of interest to know if the results reported here can be further improved with other FLT3 inhibitors.” 



Oñate G, Pratcorona M, Garrido A, et al. Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort. Blood Cancer J. 2023;13(1):69. doi:10.1038/s41408-023-00839-1.