# Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome

## TL;DR

Adding midostaurin to decitabine treatment for older patients with AML or MDS who cannot tolerate intensive chemotherapy does not improve outcomes.

## Contribution

This study evaluates the efficacy of midostaurin in combination with decitabine for unfit AML/MDS patients, regardless of FLT3 mutations.

## Key findings

- Midostaurin addition was well tolerated but did not improve response rates or survival.
- The decitabine alone group had higher complete remission rates and longer median overall survival.
- Early death rates were similar between the two treatment groups.

## Abstract

The treatment of older patients with acute myeloid leukemia (AML) considered unfit for receiving intensive chemotherapy is challenging. Based on the hypothesis that addition of the broad tyrosine kinase inhibitor (TKI) midostaurin could improve the response to hypomethylating agents, irrespective of FLT3 gene mutational status, we conducted a randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to a 10-day schedule of decitabine in unfit (i.e. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≥ 3) AML and higher risk myelodysplasia (MDS) patients (HOVON155 trial). In total, 140 eligible patients were randomly (1:1) assigned to treatment with 10-days of decitabine alone (N = 70) or combined with midostaurin (50 mg bid;starting the day following the last dose of decitabine), (N = 70). Addition of midostaurin was well tolerated and the number of AEs was comparable for both treatment arms. Early death rates (< 30 days) were similar as well (10%). In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.

The online version contains supplementary material available at 10.1007/s00277-024-06033-y.

Midostaurin added to 10-day decitabine does not improve response nor survival in patients with newly diagnosed, FLT3 mutation agnostic, AML unsuitable for intensive chemotherapy.

Midostaurin added to 10-day decitabine does not improve response nor survival in patients with newly diagnosed, FLT3 mutation agnostic, AML unsuitable for intensive chemotherapy.

The online version contains supplementary material available at 10.1007/s00277-024-06033-y.