Schlenk, Richard F. and Weber, Daniela and Fiedler, Walter and Salih, Helmut R. and Wulf, Gerald and Salwender, Hans and Schroeder, Thomas and Kindler, Thomas and Luebber, Michael and Wolf, Dominik and Westermann, Joerg and Kraemer, Doris and Goetze, Katharina S. and Horst, Heinz-August and Krauter, Juergen and Girschikofsky, Michael and Ringhoffer, Mark and Suedhoff, Thomas and Held, Gerhard and Derigs, Hans-Guenter and Schroers, Roland and Greil, Richard and Griesshammer, Martin and Lange, Elisabeth and Burchardt, Alexander and Martens, Uwe and Hertenstein, Bernd and Marretta, Lore and Heuser, Michael and Thol, Felicitas and Gaidzik, Verena and Herr, Wolfgang and Krzykalla, Julia and Benner, Axel and Doehner, Konstanze and Ganser, Arnold and Paschka, Peter and Doehner, Hartmut (2019) Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. BLOOD, 133 (8). pp. 840-851. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANS-RETINOIC ACID; INTERNAL TANDEM DUPLICATION; NPM1 MUTATIONS; ADULT PATIENTS; AML; IMPACT; OLDER; TRANSPLANTATION; RECOMMENDATIONS; CLASSIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2020 06:45 |
| Last Modified: | 17 Apr 2020 06:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27527 |
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