2026 ASH®
Annual Meeting & Exposition December 12-15, 2026 ▪ New Orleans, Louisiana

Begin New Search

Paper Details

Abstracts, authors, affiliations, and disclosures.

SESSION

615. Acute Myeloid Leukemias: Clinical and Epidemiological: Novel Combination Regimens for Fit and Less-fit AML Patients

Program: Oral Abstract Session
Saturday, December 12, 2026
09:30 a.m. - 11:00 a.m.
MCCNO - Great Hall BC

KEYWORDS

Treatment Considerations, Combination Therapy, Drug Development, Clinical Practice (Health Services and Quality), Patient Safety, Practice Models, Diseases, Myeloid Malignancies, Acute Myeloid Malignancies, Measurable Residual Disease, Research, AML, Clinical Research, Clinical Trials, Health Outcomes Research, Study Population, Human, Adult
PAPER

56 Subgroup analysis of gilteritinib versus midostaurin in newly diagnosed FLT3-mutated acute myeloid leukemia (FLT3mut+ AML): An explorative analysis from the HOVON156/AMLSG28-18/pasha trial

AUTHORS

Marc Raaijmakers, MD, Gert J. Ossenkoppele, MD2, Patrycja L. Gradowska3, Christian Recher, MD, PhD4, Andrew H. Wei, MBBS, PhD5, Marie-Anne Hospital6, Pierre-Yves Dumas, MD, PhD7, Emanuele Ammatuna, MD, Ph.D8, Hervé Dombret9, Andrea Lenartova, MD, PhD10, Thomas Pabst, MD11, Franziska Westendorf, MD12, Michael WM Kühn13, Thomas Cluzeau, MD, PhD14, Anna van Rhenen, MD, PhD15, Pierre Peterlin, MD16, Martin Carre, MD17, Rinske S. Boersma18, Jean-Baptiste Micol, MD, PhD19, Marjolein Donker, MD20, Maaike Söhne21, Marc Bernard, MD22, Laimonas Griškevicius, MD23, Maher Hanoun, MD24, Markus G. Manz, MD25, Joerg Westermann, Prof. Dr. med.26, Peter E. Westerweel, MD, PhD27, Benjamin Bailly28, Arnold Ganser I, MD29, Johan A. Maertens, MD30, Juliette Lambert31, Adriano Salaroli I32, Geerte L. van Sluis, MD33, Lino L Teichmann, MD34, Lidwine Tick35, Yohan Desbrosses, MD, PhD36, Romain Guieze, PhD37, Mael Heiblig, MD38, Sylvain Thépot, MD39, Luca Inchiappa, MD40, Danielle Venema, MD41, Claudia Lengerke, MD42, Mark Ringhoffer43, Hans-Juergen Salwender, MD44, Roland Schroers45, Andreas Voss46, Ashish Bajel, MD47, Anne Banos, MD48, Amine Belhabri, MD49, Thorsten Braun50, Jordi Esteve, MD, PhD51, Michael Fay52, Jörg Halter53, Gunnar Juliusson, MD, PhD54, Bruno Lioure55, Jean Malfuson56, Paula Marlton, MBBS, FRACP, FRCPA57, Kai Wille58, Friederike Wortmann59, Andrius Zucenka, MD60, Mika Kontro, MD, PhD61, Jorge Sierra, MD, PhD62, Bjørn Gjertsen, MD, PhD63, Martin Hoglund, MD, PhD64, Janusz Krawczyk65, Bas J Wouters, MD, PhD66, Wensheng He67, Nahla Hasabou, MD68, Caroline Chen, MD, MS69, Alexandra Heinloth, MD70, Jason Hill71, Jennifer Sugg72, Annelies Verbrugge73, Jacqueline Cloos, MD74, Michaela Feuring, MD75, Felicitas R Thol, MD76, Konstanze Döhner, MD77, Peter JM Valk, PhD78, Anika Schrade79, Brigitta AG Schuthof, MSc80, Petra B Cornelisse81, Gerwin A. Huls, MD, PhD82, Bob Lowenberg, MD,PhD83, Hartmut Döhner, MD84

AFFILIATIONS

1 Department of Hematology, Erasmus MC Cancer Institute and Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
2 Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, Netherlands
3 Department of Hematology, Erasmus MC Cancer Institute and Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands, HOVON Foundation, Rotterdam, Netherlands
4 Hematology Department, Université de Toulouse, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
5 Department of Hematology, The Peter Mac Callum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia
6 Hematology Department, Institut Paoli-Calmettes, Marseille, France
7 Centre Hospitalier Universitaire de Bordeaux, Service d'Hématologie Clinique et de Thérapie Cellulaire, Bordeaux, France
8 Department of Hematology, University Medical Center Groningen, Groningen, Netherlands
9 Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
10 Department of Hematology, Oslo University Hospital, Oslo, Norway
11 Department of Medical Oncology, University Hospital, Inselspital, Bern, Switzerland
12 Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
13 Department of Hematology and Medical Oncology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
14 Hematology Department, Nice University Hospital, Nice, France
15 Department of Hematology, Cancer Center, University Medical Center Utrecht, Utrecht, Netherlands
16 Hematology Department, Hôtel-Dieu University Hospital, Nantes, France
17 Service d'hématologie, CHU Grenoble Alpes, La Tronche, France
18 Department of Hematology, Amphia Hospital, Breda, Netherlands
19 Département d’hématologie, Gustave Roussy, Villejuif, France
20 Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, Netherlands
21 St Antonius Ziekenhuis, Nieuwegein, Netherlands
22 Department of Hematology, L'Hôpital Pontchaillou, CHU de Rennes, Rennes, France
23 Hematology, Oncology, and Transfusion Medicine Center, National Cancer Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
24 Department of Internal Medicine I, Klinikum Bremen Mitte, Bremen, Germany, Bremen, Germany
25 Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
26 Charité-University Medical Center, Campus Virchow Clinic, Berlin, Germany
27 Department of Hematology, Albert Schweitzer Hospital, Dordrecht, Netherlands
28 Hôpital de Jolimont, Haine-Saint-Paul, Belgium
29 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
30 Department of Hematology, University Hospitals Leuven, Leuven, Belgium
31 Service d'Hématologie Centre Hospitalier de Versailles, Commissariat à l'Energie Atomique, University de Versailles Paris-Saclay, Le Chesnay, France
32 Department of Hematology, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium
33 Isala Clinics, Department of Internal Medicine, Zwolle, Netherlands
34 Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Bonn, Germany
35 Department of Hematology, Maxima Medisch Centrum, Veldhoven, Netherlands
36 Service d'Hématologie, Centre Hospitalier Universitaire de Besançon, Besançon, France
37 CHU Clermont-Ferrand, Clermont-Ferrand, France
38 Hematology Department, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France
39 Maladies du Sang, CHU d’Angers, FHU GOAL INSERM CRCI2NA, Angers, France
40 Medical Oncology Department, Centre Antoine Lacassagne, Nice, France
41 Haga Ziekenhuis Hospital, The Hague, Netherlands
42 Universitätsklinikum Tübingen, Tübingen, Germany
43 Municipal Hospital Karlsruhe, Karlsruhe, Germany
44 Asklepios Tumorzentrum Hamburg, AK Altona and AK St Georg, Hamburg, Germany
45 Department of Hematology, Oncology, Stem Cell Transplantation and Cellular Therapy, Knappschaft Kliniken Universitätsklinikum Bochum, Ruhr University, Bochum, Germany
46 Department of Oncology and Hematology, University Clinic Oldenburg, 26133, Oldenburg, Germany
47 Department of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, VIC, Australia
48 Department of Hematology, Centre Hospitalier de la Côte Basque, Bayonne, France
49 Service d'Hématologie, Centre Léon-Bérard, Lyon, France
50 Department of Hematology, Université Paris Nord, Hôpital Avicenne, AP-HP, Bobigny, France
51 Hematology Department, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain
52 Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
53 Department of Hematology, University Hospital Basel, Basel, Switzerland
54 Skane University Hospital, Lund University, Lund, Sweden
55 Hematology, Hopitaux Universitaires de Strasbourg, Strasbourg, France
56 Department of Hematology, Percy Armed Forces Hospital, Clamart, France
57 Department of Haematology, Princess Alexandra Hospital and University of Queensland, Brisbane, Australia
58 University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University of Bochum, Minden, Germany
59 Department of Hematology and Oncology, University Medical Center Schleswig-Holstein (UKSH), University Cancer Center Schleswig-Holstein (UCCSH), Campus Luebeck and University of Lübeck, Lübeck, Germany
60 Department of Hematology and Oncology, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Hematology, Oncology, and Transfusion Medicine Center, National Cancer Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
61 Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
62 Department of Hematology, Hospital Santa Creu i Sant Pau, IR-Sant Pau, Universitat Autonoma of Barcelona, Barcelona, Spain
63 Department of Clinical Science, University of Bergen, Bergen, Norway
64 Department of Medical Sciences, Section of Hematology, Uppsala University, Uppsala, Sweden
65 Haematology Department, University Hospital Galway, Saolta University Healthcare Group, Galway, Ireland
66 Department of Hematology, Erasmus MC Cancer Institute and Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
67 Astellas Pharma Inc., Northbrook, IL, United States
68 Astellas Pharma Inc., Northbrook, IL, United States
69 Astellas Pharma Inc., Northbrook, IL, United States
70 Astellas Pharma Inc., Northbrook, IL, United States
71 Astellas Pharma Inc., Northbrook, IL, United States
72 Astellas Pharma Inc., Northbrook, IL, United States
73 HOVON Foundation, Rotterdam, Netherlands
74 Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, Netherlands
75 Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany
76 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
77 Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany
78 Department of Hematology, Erasmus MC Cancer Institute and Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
79 Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany
80 HOVON Foundation, Rotterdam, Netherlands
81 HOVON Foundation, Rotterdam, Netherlands
82 Department of Hematology, University Medical Center Groningen, Groningen, Netherlands
83 Department of Hematology, Erasmus MC Cancer Institute and Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
84 Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany

ABSTRACT

Background: HOVON156/AMLSG28-18/PASHA is the first phase 3 trial directly comparing the first generation FLT3-inhibitor midostaurin to a second generation, more specific and potent, FLT3-inhibitor gilteritinib, plus intensive chemotherapy, in newly-diagnosed (ND) FLT3-internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutated AML. While the primary analysis at 43.2 months median follow-up revealed no difference in overall survival (OS) as the primary endpoint (hazard ratio [HR] 1.02, p=0.864), the secondary endpoints of event-free survival (EFS) and relapse-free survival (RFS) both numerically favored gilteritinib (EFS: HR 0.83, nominal p=0.052; RFS: HR 0.68, nominal p=0.003) (Raaijmakers et al. Late breaking abstract, EHA 2026). We present subgroup analyses exploring variations in treatment effect across different subgroups of patients (pts) from the HOVON156/AMLSG28-18/PASHA trial.

Methods: Eligible pts (≥18 years of age, with ND FLT3mut+ AML) were randomized 1:1 to receive gilteritinib or midostaurin, plus induction chemotherapy, followed by consolidation chemotherapy (with gilteritinib or midostaurin) and/or allogeneic hematopoietic stem cell transplant, and up to 12 cycles of single-agent maintenance therapy. Pre-planned subgroup analyses were conducted for OS and EFS; RFS was analyzed post hoc. For each subgroup, defined by pt age, sex, WHO performance status (PS), disease status, ELN2017 genetic risk, FLT3 mutation and NPM1 mutational status, HR and 95% confidence interval (CI) were calculated by the unstratified Cox proportional hazards model; unstratified log-rank test was used for comparisons. There was no adjustment for multiplicity; all subgroup p-values are nominal.

Results: A total of 768 pts with AML were randomized (gilteritinib, n=384; midostaurin, n=384). Baseline characteristics were balanced between treatment arms and generally reflective of the FLT3mut+ population. Overall, 303 pts in the gilteritinib arm and 320 pts in the midostaurin arm achieved complete remission (CR) after induction and were evaluable for RFS.  

OS was similar between the gilteritinib and midostaurin arms across all subgroups, notably those defined by age (≤60 years: HR 1.07 [95% CI: 0.76-1.52], p=0.691; ≥61 years: HR 1.02 [95% CI: 0.76–1.37], p=0.889), FLT3 mutational type (FLT3-ITD AR <0.5: HR 1.17 [95% CI: 0.78–1.77], p=0.443; FLT3-ITD AR ≥0.5: HR 1.05 [95% CI: 0.76–1.44], p=0.776; FLT3-TKD mutation: HR 0.86 [95% CI: 0.51–1.44], p=0.569), NPM1 mutational status (mutated: HR 0.93 [95% CI: 0.67–1.28], p=0.640; wildtype: HR 1.20 [95% CI: 0.87–1.65], p=0.269), and ELN2017 genetic risk (favorable: HR 0.91 [95% CI: 0.59–1.43], p=0.692; intermediate: HR 0.90 [95% CI: 0.63–1.30], p=0.588; adverse: HR 1.31 [95% CI: 0.90–1.91], p=0.153).

For RFS, a positive treatment effect in favor of gilteritinib was observed across most subgroups, with a nominal improvement (p<0.050) found in patients ≤60 years (HR 0.56 [95% CI: 0.40–0.81], p=0.001), ELN2017 intermediate-risk disease (HR 0.56 [95% CI: 0.37–0.84], p=0.004), FLT3-ITD AR ≥0.5 (HR 0.59 [95% CI: 0.41–0.85], p=0.005), NPM1 mutational status (HR 0.61 [95% CI: 0.43–0.86], p=0.005), NPM1mut/FLT3-ITD AR ≥0.5 (HR 0.47 [95% CI: 0.29–0.78], p=0.003), female pts (HR 0.55 [95% CI: 0.38–0.80], p=0.001), pts with a PS of 0 (HR 0.56 [95% CI: 0.37–0.84], p=0.004), PS of 1 (HR 0.69 [95% CI: 0.49–0.97], p=0.030), and de novo AML (HR 0.63 [95% CI: 0.48–0.83], p=0.001).

For EFS, most of the subgroups favored gilteritinib (HR <1.0) with a nominal p-value <0.050 observed for pts ≤60 years (HR 0.76 [95% CI: 0.57–1.00], p=0.042), ELN2017 intermediate-risk (HR 0.69 [95% CI: 0.50–0.95], p=0.020), FLT3-ITD AR ≥0.5 (HR 0.75 [95% CI: 0.57–1.00], p=0.039), and NPM1mFLT3-ITD AR ≥0.5 (HR 0.65 [95% CI: 0.44–0.96], p=0.022).

Conclusions: The HOVON156/AMLSG28-18/PASHA trial showed no difference in OS between gilteritinib and midostaurin across all predefined subgroups of pts with ND FLT3mut+ AML. In contrast, RFS benefit with gilteritinib vs midostaurin was consistently observed across most subgroups, particularly in pts ≤60 years of age, those with ELN2017 intermediate-risk disease, and pts with NPM1-mutated AML and FLT3-ITD AR ≥0.5. While exploratory, these findings support the greater antileukemic activity of the second-generation FLT3 inhibitor gilteritinib compared with midostaurin.

DISCLOSURES

Marc Raaijmakers, MD: Astellas - Honoraria; Daiichi Sankyo - Research Funding; Daiichi Sankyo - Consultancy (Includes expert testimony); Astellas - Consultancy (Includes expert testimony)
Begin New Search