Midostaurin in patients with indolent systemic mastocytosis: An open-label phase 2 trial

• Published in: Journal of allergy and clinical immunology Vol. 142; no. 3; pp. 1006 - 1008.e7
• Main Authors: van Anrooij, Bjorn, Oude Elberink, Joanne N.G., Span, Lambert F.R., de Monchy, Jan G.R., Rosati, Stefano, Mulder, André B., Kluin-Nelemans, Johanna C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018; Elsevier Limited
• Subjects: Anaphylaxis; Bone marrow; Mastocytosis; Patients; Pruritus; Quality of life; Response rates
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2018.06.003

To the Editor: Indolent systemic mastocytosis (ISM) is the most prevalent form of mastocytosis and characterized by mast cell infiltration of, in particular, the bone marrow, gastrointestinal tract and skin but by definition no resulting organ dysfunction, setting it apart from advanced systemic mastocytosis (SM).1 For most patients with ISM, mast cell burden will remain stable throughout a near-normal life expectancy.2 More than 70% of patients with ISM experience an impaired quality of life because of refractory symptoms caused by mast cell mediator release, illustrating the large unmet therapeutic need.3 Midostaurin is a multikinase inhibitor capable of inhibiting the kinase activity of both wild-type and D816V mutated KIT.4 Studies in patients with advanced SM demonstrated a rapid response of mast cell mediator symptoms, suggesting a potential use in patients with ISM.5 Therefore we conducted an open-label, nonrandomized, single-center, phase 2 trial to study the efficacy and safety of midostaurin in 20 patients with ISM with severe mast cell activation symptoms refractory to antihistamine medication. [...]patients with serious comorbidity expected to interfere with therapy and follow-up compliance were excluded. According to protocol, all patients stopped midostaurin at week 24. [...]we find midostaurin to be an effective, fast-acting, relatively safe, and reasonably tolerable treatment modality for patients with ISM with severe mediator release symptoms or skin infiltration.