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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. and Weber, D. and Krzykalla, J. and Fiedler, W. and Wulf, G.G. and Salih, H.R. and Lübbert, M. and Kühn, M. and Schroeder, T. and Salwender, H. and Götze, K.S. and Westermann, J. and Fransecky, L. and Mayer, K. and Hertenstein, B. and Ringhoffer, M. and Tischler, H.J. and Machherndl-Spandl, S. and Schrade, A. and Paschka, P. and Gaidzik, V.I. and Theis, F. and Thol, F.R. and Heuser, M. and Schlenk, R.F. and Bullinger, L. and Saadati, M. and Benner, A. and Larson, R.A. and Stone, R.M. and 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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