Midostaurin is a multikinase inhibitor that includes mutant and nonmutant KIT D816V as a target. Its use in patients with advanced systemic mastocytosis, including mast-cell leukemia, produced responses in 60%, with a median overall survival of 28.7 months. Systemic mastocytosis is a myeloid neoplasm that is caused by the accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin. 1 The KIT D816V mutation, which is detected in approximately 90% of patients, encodes a constitutively activated receptor tyrosine kinase that drives disease pathogenesis. 2 , 3 The World Health Organization (WHO) classification of advanced systemic mastocytosis includes aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm (also termed systemic mastocytosis with an associated hematologic non–mast-cell-lineage disease), and mast-cell leukemia (Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). 4 Symptoms are caused . . .