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| Item Type: | Article |
|---|---|
| Title: | Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications |
| Creators Name: | Döhner, H., Weber, D., Krzykalla, J., Fiedler, W., Wulf, G.G., Salih, H.R., Lübbert, M., Kühn, M., Schroeder, T., Salwender, H., Götze, K.S., Westermann, J., Fransecky, L., Mayer, K., Hertenstein, B., Ringhoffer, M., Tischler, H.J., Machherndl-Spandl, S., Schrade, A., Paschka, P., Gaidzik, V.I., Theis, F., Thol, F.R., Heuser, M., Schlenk, R.F., Bullinger, L., Saadati, M., Benner, A., Larson, R.A., Stone, R.M., Döhner, K. and Ganser, A. |
| Abstract: | We conducted a single-arm phase-II trial (AMLSG 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a one-year midostaurin maintenance therapy in adult patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (ITD). Patients 18-70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free (EFS) and overall survival (OS). Results were compared to a historical cohort of 415 patients treated on 5 prior AMLSG trials; statistical analysis was performed using a double-robust adjustment with propensity score weighting and covariate adjustment. Results were also compared to patients (18-59yrs) treated on the placebo arm of the CALGB 10603/RATIFY trial. The trial accrued 440 patients (18-60yrs, n=312; 61-70yrs, n=128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared to the AMLSG control (HR 0.55; P<0.001); both in younger (HR 0.59; P<0.001) and older patients (HR 0.42; P<0.001). Multivariate analysis also showed a significant beneficial effect on OS compared to the AMLSG control (HR 0.57; P<0.001) as well as to the CALGB 10603/RATIFY trial (HR 0.71; p=0.005). The treatment effect of midostaurin remained significant in sensitivity analysis including allogeneic HCT as a time-dependent covariate. Addition of midostaurin to chemotherapy was safe in younger and older patients. In comparison to historical controls, the addition of midostaurin to intensive therapy led to a significant improvement in outcome in younger and older patients with AML and FLT3-ITD. The AMLSG 16-10 trial is registered at clinicaltrialsregistry.eu (Eudra-CT number 2011-003168-63) and clinicaltrials.gov (NCT01477606). |
| Keywords: | Acute Myeloid Leukemia, Midostaurin, FLT3 |
| Source: | Blood Advances |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Volume: | 6 |
| Number: | 18 |
| Page Range: | 5345-5355 |
| Date: | 27 September 2022 |
| Additional Information: | Copyright © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
| Official Publication: | https://doi.org/10.1182/bloodadvances.2022007223 |
| PubMed: | View item in PubMed |
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