Midostaurin in advanced systemic mastocytosis: A systematic review and meta-analysis.

Abstract

e19084 Background: Midostaurin, an oral multikinase inhibitor including inhibition of KIT D816V, is approved for the treatment of advanced systemic mastocytosis (SM). Few studies have investigated the use of midostaurin in patients with advanced SM, but the data on its efficacy and safety in this population remains limited and uncertain. Therefore, we conducted this systematic review and meta-analysis to better assess the efficacy and safety of midostaurin in advanced SM. Methods: We systematically searched the following databases: PubMed/MEDLINE, Embase, and Cochrane through February 02, 2022, to include all studies that assessed the effect of midostaurin on clinical outcomes of patients with advanced SM. Our primary outcome was the overall response rate (ORR). The secondary outcomes included the rates of progressive disease (PD), stable disease (SD), and treatment discontinuation due to adverse events (AEs). All statistical analyses were performed using Open Meta Analyst (CEBM, University of Oxford). Pooled rates and corresponding 95% confidence intervals (CI) were calculated using DerSimonian-Laird/Random-effects approach. Results: Four studies (two clinical trials and two observational studies) with a total of 156 patients with advanced SM were included in the pooled analysis. The mean age of the patients was 59.6±15.8 years, and males represented 64.7% of total patients. The most common subtype of advanced SM was SM associated with hematological neoplasm (59%) followed by aggressive SM (23.1%). Three studies reported the KIT D816V mutation status, and 85.2% of patients were positive for KIT D816V mutation. The mean duration of treatment with midostaurin was 10±15.3 months. The pooled ORR was 60% (95% CI 46.5%-73.5%) over a mean follow-up duration of 41.1±38.7 months. The PD and SD rates were 12.8% (95% CI 7.6%-18%) and 10.6% (5.3%-15.9%), respectively. Treatment discontinuation due to AEs occurred in 25.6% (95% CI 18.8%-32.4%). The most common hematological grade ≥3 treatment-related AE was anemia (29%), while fatigue (7.1%) was the most common non-hematological grade ≥3 treatment-related AE. Conclusions: Our study demonstrated that midostaurin is very effective in patients with advanced SM with an acceptable safety profile. Our meta-analysis is hampered by a limited number of studies, a small sample size, and a lack of a control group. Future large-scale comparative studies are warranted to evaluate the efficacy and safety of midostaurin in these patients.