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

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.

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Publication Details

Journal
Annals of Hematology
Published
2024-10-05
DOI
https://doi.org/10.1007/s00277-024-06033-y
Primary Topic
Acute Myeloid Leukemia Research
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article
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article

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

Rinske Boersma, Raoul A. Fakkert, Marjan J. Cruijsen, Anna van Rhenen et al.
Annals of Hematology
Acute Myeloid Leukemia Research
article

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

Rinske Boersma, Raoul A. Fakkert, Marjan J. Cruijsen, Anna van Rhenen, Suzan de Jonge, Peter E. Westerweel, Mels Hoogendoorn, A H E Herbers, Bob Löwenberg, Saskia K. Klein, Lidwine Winnifred Tick, Otto Visser, Dries Deeren, Dimitri A. Breems, Dana Chiţu, Benjamin Bailly, Jacqueline J Cloos, Emanuele Ammatuna, Peter J.M. Valk, Jeannine Refos, Gerwin A. Huls, Gert Jan Ossenkoppele, M. L. H. Cuijpers, E.F.M. Posthuma
article en

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.

Annals of HematologyVol. 104(1)
University Medical Center Groningen (NL), Radboud University Nijmegen (NL), Catharina Ziekenhuis (NL), Erasmus MC (NL), Medisch Centrum Leeuwarden (NL), University Medical Center Utrecht (NL), Albert Schweitzer Ziekenhuis (NL), Reinier de Graaf Hospital (NL), Amphia Ziekenhuis (NL), Hôpital de Jolimont (BE), ZNA Middelheim Hospital (BE), Canisius-Wilhelmina Ziekenhuis (NL), Máxima Medisch Centrum (NL), AZ Delta (BE), Hovon (NL), Isala (NL), Erasmus MC Cancer Institute (NL), Rijnstate Hospital (NL), Meander Medisch Centrum (NL), Jeroen Bosch Ziekenhuis (NL), Cancer Center Amsterdam (NL), Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
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