Midostaurin added to chemotherapy and continued single agent maintenance therapy in acute myeloid leukemia with FLT3-ITD
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Midostaurin added to chemotherapy and continued single agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. / Schlenk, Richard F; Weber, Daniela; Fiedler, Walter; Salih, Helmut R; Wulf, Gerald; Salwender, Hans; Schroeder, Thomas; Kindler, Thomas; Lübbert, Michael; Wolf, Dominik; Westermann, Jörg; Kraemer, Doris; Götze, Katharina S; Horst, Heinz-August; Krauter, Jürgen; Girschikofsky, Michael; Ringhoffer, Mark; Südhoff, Thomas; Held, Gerhard; Derigs, Hans-Günter; Schroers, Roland; Greil, Richard; Grießhammer, Martin; Lange, Elisabeth; Burchardt, Alexander; Martens, Uwe; Hertenstein, Bernd; Marretta, Lore; Heuser, Michael; Thol, Felicitas; Gaidzik, Verena I; Herr, Wolfgang; Krzykalla, Julia; Benner, Axel; Döhner, Konstanze; Ganser, Arnold; Paschka, Peter; Döhner, Hartmut.
in: BLOOD, Jahrgang 133, Nr. 8, 21.02.2019, S. 840-851.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Midostaurin added to chemotherapy and continued single agent maintenance therapy in acute myeloid leukemia with FLT3-ITD
AU - Schlenk, Richard F
AU - Weber, Daniela
AU - Fiedler, Walter
AU - Salih, Helmut R
AU - Wulf, Gerald
AU - Salwender, Hans
AU - Schroeder, Thomas
AU - Kindler, Thomas
AU - Lübbert, Michael
AU - Wolf, Dominik
AU - Westermann, Jörg
AU - Kraemer, Doris
AU - Götze, Katharina S
AU - Horst, Heinz-August
AU - Krauter, Jürgen
AU - Girschikofsky, Michael
AU - Ringhoffer, Mark
AU - Südhoff, Thomas
AU - Held, Gerhard
AU - Derigs, Hans-Günter
AU - Schroers, Roland
AU - Greil, Richard
AU - Grießhammer, Martin
AU - Lange, Elisabeth
AU - Burchardt, Alexander
AU - Martens, Uwe
AU - Hertenstein, Bernd
AU - Marretta, Lore
AU - Heuser, Michael
AU - Thol, Felicitas
AU - Gaidzik, Verena I
AU - Herr, Wolfgang
AU - Krzykalla, Julia
AU - Benner, Axel
AU - Döhner, Konstanze
AU - Ganser, Arnold
AU - Paschka, Peter
AU - Döhner, Hartmut
N1 - Copyright © 2018 American Society of Hematology.
PY - 2019/2/21
Y1 - 2019/2/21
N2 - Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.
AB - Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3-ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606.
KW - Journal Article
U2 - 10.1182/blood-2018-08-869453
DO - 10.1182/blood-2018-08-869453
M3 - SCORING: Journal article
C2 - 30563875
VL - 133
SP - 840
EP - 851
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 8
ER -
