Patient-tailored azacitidine, venetoclax and gilteritinib triplet therapy appear to improve tolerability while preserving encouraging clinical outcomes in FLT3-mutated relapsed/refractory AML.
11 affiliations
- 1Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden. [email protected].
- 2Department of Hematology, Karolinska University Hospital, Stockholm, Sweden. [email protected].
- 3Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
- 4Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
- 5Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
- 6Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
- 7Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
- 8Department of Medicine, Halland Hospital, Halmstad, Sweden.
- 9Department of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden.
- 10Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden. [email protected].
- 11Department of Hematology, Karolinska University Hospital, Stockholm, Sweden. [email protected].
Abstract
FLT3-mutated acute myeloid leukemia (AML) is associated with high relapse rates and treatment resistance. Triplet therapy with azacitidine (AZA), venetoclax (VEN), and the FLT3 inhibitor gilteritinib (GILT) yields high response rates but is limited by myelosuppression and infections. We conducted a multicenter retrospective study of 29 FLT3-mutated AML patients treated with GILT-triplets. The primary endpoint was overall survival (OS); secondary endpoints event-free survival (EFS) and time to neutrophil and platelet recovery. Patients received one of three regimens: concomitant triplet therapy (Group 1); concomitant AZA + VEN followed by concomitant VEN+GILT (Group 2); or overlapping AZA + VEN followed by GILT monotherapy (Group 3). For the entire cohort median OS was not reached after more than five years of follow-up. High response rates were observed across all schedules. Limiting concomitant exposure reduced myelosuppression and decreased infectious complications compared with full triplet therapy. Median OS was not reached in Groups 1 and 2 after three years, whereas Group 3 had a median OS of 18 months. Median EFS was 40.5 months in Group 1 and was not reached at five years in Group 2, compared with 11.5 months in Group 3. Our data suggest that reducing the duration of triple-drug overlap may improve tolerability without compromising clinical outcomes.
Related
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BibTeX
@article{kvissberg2026patienttailored,
title = {{Patient-tailored azacitidine, venetoclax and gilteritinib triplet therapy appear to improve tolerability while preserving encouraging clinical outcomes in FLT3-mutated relapsed/refractory AML.}},
author = {Matilda Arvidsson Kvissberg and Christer Nilsson and Niklas Landberg and Albin Österroos and Aristea Papageorgiou and Bertil Uggla and Vladimir Lazarevic and Stefan Deneberg and Martin Jädersten},
journal = {Annals of hematology},
year = {2026},
month = oct,
doi = {10.1007/s00277-026-07297-2},
url = {https://europepmc.org/article/MED/42909668},
note = {CC BY},
}
RIS
TY - JOUR
TI - Patient-tailored azacitidine, venetoclax and gilteritinib triplet therapy appear to improve tolerability while preserving encouraging clinical outcomes in FLT3-mutated relapsed/refractory AML.
AU - Matilda Arvidsson Kvissberg
AU - Christer Nilsson
AU - Niklas Landberg
AU - Albin Österroos
AU - Aristea Papageorgiou
AU - Bertil Uggla
AU - Vladimir Lazarevic
AU - Stefan Deneberg
AU - Martin Jädersten
PY - 2026
DA - 2026/10/23
JO - Annals of hematology
DO - 10.1007/s00277-026-07297-2
UR - https://europepmc.org/article/MED/42909668
AB - FLT3-mutated acute myeloid leukemia (AML) is associated with high relapse rates and treatment resistance. Triplet therapy with azacitidine (AZA), venetoclax (VEN), and the FLT3 inhibitor gilteritinib (GILT) yields high response rates but is limited by myelosuppression and infections. We conducted a multicenter retrospective study of 29 FLT3-mutated AML patients treated with GILT-triplets. The primary endpoint was overall survival (OS); secondary endpoints event-free survival (EFS) and time to neutrophil and platelet recovery. Patients received one of three regimens: concomitant triplet therapy (Group 1); concomitant AZA + VEN followed by concomitant VEN+GILT (Group 2); or overlapping AZA + VEN followed by GILT monotherapy (Group 3). For the entire cohort median OS was not reached after more than five years of follow-up. High response rates were observed across all schedules. Limiting concomitant exposure reduced myelosuppression and decreased infectious complications compared with full triplet therapy. Median OS was not reached in Groups 1 and 2 after three years, whereas Group 3 had a median OS of 18 months. Median EFS was 40.5 months in Group 1 and was not reached at five years in Group 2, compared with 11.5 months in Group 3. Our data suggest that reducing the duration of triple-drug overlap may improve tolerability without compromising clinical outcomes.
SN - 0939-5555
SN - 1432-0584
ER -