@article{be1545d193ec4083a57038b904ee2115,
title = "Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis",
abstract = "Background: Advanced systemic mastocytosis (advSM) is characterized by presence of the KIT D816V mutation and pathologic accumulation of neoplastic mast cells (MCs) in various tissues, leading to severe symptoms and organ damage (eg, cytopenias, liver dysfunction, portal hypertension, malabsorption, and weight loss). Treatment with midostaurin, an orally active multikinase/KIT inhibitor now approved for advSM in the United States and the European Union, resulted in a high rate of response accompanied by reduced MC infiltration of the bone marrow and lowered serum tryptase level. Objective: We aimed to determine whether midostaurin improves health-related quality of life (QOL) and MC mediator–related symptoms in patients with advSM. Methods: In 116 patients with systemic mastocytosis (89 patients with advSM fulfilling the strict inclusion criteria of the D2201 study [ClinicalTrials.gov identifier NCT00782067]), QOL and symptom burden were assessed during treatment with midostaurin by using the 12-Item Short-Form Health Survey (SF-12) and the Memorial Symptom Assessment Scale patient-reported questionnaires, respectively. MC mediator–related symptoms were evaluated by using a specific physician-reported questionnaire. Results: Over the first 6 cycles of treatment with midostaurin (ie, 6 months), patients experienced significant improvements in total SF-12 and Memorial Symptom Assessment Scale scores, as well as in subscores of each instrument. These improvements were durable during 36 months of follow-up. Similarly, we found substantial improvements (67%-100%) in all MC mediator–related symptoms. Conclusion: QOL and MC mediator–related symptoms significantly improve with midostaurin treatment in patients with advSM (ClinicalTrials.gov identifier, NCT00782067).",
keywords = "Advanced systemic mastocytosis, KIT mutation, mastocytosis, mediator symptoms, midostaurin, quality of life, skin lesions of mastocytosis, tryptase",
author = "Karin Hartmann and Jason Gotlib and Cem Akin and Olivier Hermine and Awan, {Farrukh T.} and Elizabeth Hexner and Mauro, {Michael J.} and Menssen, {Hans D.} and Suman Redhu and Stefanie Knoll and Karl Sotlar and George, {Tracy I.} and Horny, {Hans Peter} and Peter Valent and Andreas Reiter and Kluin-Nelemans, {Hanneke C.}",
note = "Funding Information: Disclosure of potential conflicts of interest. K. Hartmann is member of study steering committees for studies in systemic mastocytosis (Novartis D2201 study and Blueprint Medicines study); she has received consulting fees, honoraria, and reimbursement of travel expenses from ALK-Abell{\'o}, Allergopharma, Blueprint Medicines, Deciphera, Menarini, Novartis Pharmaceuticals Corporation, and Takeda, as well as research grants from Euroimmun and ThermoFisher. J. Gotlib is chairman and cochairman of study steering committees for studies in systemic mastocytosis (Novartis D2201 study, Blueprint Medicines study, and Deciphera study) and has received consulting fees, honoraria, and reimbursement of travel expenses from Blueprint Medicines, Deciphera, and Novartis Pharmaceuticals Corporation. C. Akin is member of a study steering committee (Novartis D2201 study) and has received consulting fees from Blueprint Medicines. F.T. Awan has received consulting fees from Genentech, AstraZeneca, AbbVie, Janssen, Pharmacyclics, Gilead Sciences, Kite Pharma, Dava Oncology, Celgene, Blueprint Medicines, and Sunesis. E. Hexner has received research support from Novartis Oncology and Blueprint Medicines. M. J. Mauro has received consulting fees, honoraria, and reimbursement of travel expenses from Bristol-Myers Squibb, Takeda, Pfizer, and Novartis, as well as institutional research support from Novartis, Bristol-Myers Squibb, and SPARC/Sun Pharma. H. Menssen, S. Redhu, and S. Knoll are employed by Novartis Pharmaceuticals Corporation and may hold stock or stock options in the company. K. Sotlar has received consulting fees, honoraria, and reimbursement of travel expenses from Novartis. T. George is member of study steering committees for studies in systemic mastocytosis (Novartis D2201 study and Blueprint Medicines study) and has received consulting fees from Blueprint Medicines, Deciphera, and Novartis Pharmaceuticals Corporation. P. Valent is member of a study steering committee in systemic mastocytosis (Novartis D2201 study) and has received consulting fees and honoraria from Novartis Pharmaceuticals Corporation, Deciphera, and Blueprint Medicines. A. Reiter is member of study steering committees for studies in systemic mastocytosis (Novartis D2201 study and Blueprint Medicines study) and has received consulting fees, honoraria, and reimbursement of travel expenses from Blueprint Medicines, Deciphera, and Novartis Pharmaceuticals Corporation, as well as research funding from Novartis Pharmaceuticals Corporation. H. C. Kluin-Nelemans has received financial support (to her department) from Novartis Pharmaceuticals Corporation. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: K.H. was supported by the German Research Council (Deutsche Forschungsgemeinschaft, project HA 2393/6-1) and intramural funding of the University of Basel. J.G. was supported by the Charles and Ann Johnson Foundation. A research grant from the Austrian Science Fund (project SFB F4704) was provided to P.V. Funding Information: K.H. was supported by the German Research Council (Deutsche Forschungsgemeinschaft, project HA 2393/6-1 ) and intramural funding of the University of Basel . J.G. was supported by the Charles and Ann Johnson Foundation . A research grant from the Austrian Science Fund (project SFB F4704 ) was provided to P.V. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = aug,
doi = "10.1016/j.jaci.2020.03.044",
language = "English (US)",
volume = "146",
pages = "356--366.e4",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "2",
}