Targeted therapy for advanced forms of systemic mastocytosis in real clinical practice

Background. Mastocytosis is a heterogeneous group of diseases that are characterized by excessive proliferation and accumulation of clonal (neoplastic) mast cells in one or more organs. Advanced variants of systemic mastocytosis (aggressive systemic mastocytosis, systemic mastocytosis associated with hematological neoplasm, and mast cell leukemia) are characterized by infiltration of organs by mast cells, which leads to organs dysfunction. Such patients require a more active approach and the use of cytoreductive therapy. Available therapeutic options include imatinib, interferon-alpha, cladribine. Only one of the targeted drugs is registered in Russia – midostaurin. Midostaurin is a potent multikinase inhibitor that is active against KIT regardless of mutation status. Midostaurin has shown its effectiveness in clinical trials, however, we know that data from real clinical practice often differ from clinical studies due to the characteristics of patients (preserved comorbid status, stable disease parameters) traditionally included in clinical trials.Aim. To evaluate the effectiveness and safety of midostaurin in patients with advanced variants of systemic mastocytosis in real clinical practice.Materials and methods. This work analyzed 13 patients (7 (54 %) men and 6 (46 %) women) who received midostaurin therapy for systemic mastocytosis (aggressive systemic mastocytosis – 9 (69 %), systemic mastocytosis associated with a hematological neoplasm – 4 (31 %)). The median age of patients when the diagnosis was verified was 73 (61–87) years, the median age when midostaurin was prescribed was 74 (61–88) years. According to the International prognostic scoring system for mastocytosis (IPSM) based on clinical variables, patients are classified as follows groups: SM1 – 1 (8 %) patient, SM2 – 3 (23 %), SM3 – 8 (61 %), SM4 – 1 (8 %).Results. As a result of therapy, clinical improvement was achieved in 10 (77 %) patients, and stabilization in 3 (23 %) patients. During midostaurin therapy, grade I–II adverse events were noted from the gastrointestinal tract: nausea in 5 patients (38 %), vomiting in 2 (15 %), diarrhea in 6 (46 %). Hematological toxicity of grade I–II was also observed: anemia in 6 (46 %) patients, thrombocytopenia in 5 (38 %) patients. The median overall survival in the group was not achieved. The 2-year overall survival rate was 75 %.Conclusion. The study results suggest the potential efficacy and safety of midostaurin in patients with aggressive systemic mastocytosis and systemic mastocytosis associated with hematological malignancies.