edoc

Efficacy and safety of midostaurin in advanced systemic mastocytosis

Gotlib, Jason and Kluin-Nelemans, Hanneke C. and George, Tracy I. and Akin, Cem and Sotlar, Karl and Hermine, Olivier and Awan, Farrukh T. and Hexner, Elizabeth and Mauro, Michael J. and Sternberg, David W. and Villeneuve, Matthieu and Huntsman Labed, Alice and Stanek, Eric J. and Hartmann, Karin and Horny, Hans-Peter and Valent, Peter and Reiter, Andreas. (2016) Efficacy and safety of midostaurin in advanced systemic mastocytosis. The New England Journal of Medicine, 374 (26). pp. 2530-2541.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/70750/

Downloads: Statistics Overview

Abstract

Advanced systemic mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis.; We conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive systemic mastocytosis, 57 had systemic mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response.; The overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced systemic mastocytosis, KIT mutation status, or exposure to previous therapy. The median best percentage changes in bone marrow mast-cell burden and serum tryptase level were -59% and -58%, respectively. The median overall survival was 28.7 months, and the median progression-free survival was 14.1 months. Among the 16 patients with mast-cell leukemia, the median overall survival was 9.4 months (95% CI, 7.5 to not estimated). Dose reduction owing to toxic effects occurred in 56% of the patients; re-escalation to the starting dose was feasible in 32% of those patients. The most frequent adverse events were low-grade nausea, vomiting, and diarrhea. New or worsening grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 24%, 41%, and 29% of the patients, respectively, mostly in those with preexisting cytopenias.; In this open-label study, midostaurin showed efficacy in patients with advanced systemic mastocytosis, including the highly fatal variant mast-cell leukemia. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT00782067.).
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1533-4406
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 May 2020 20:33
Deposited On:17 May 2020 20:33

Repository Staff Only: item control page