- D1.531 - Avapritinib in Indolent Systemic Mastocytosis: Real-world Data from a Greek Case Series

Indolent Systemic Mastocytosis (ISM) is a clonal mast cell disease driven by the KIT D816V mutation in most adult cases. Patients with ISM often experience a significant burden of symptoms that are frequently insufficiently controlled with best supportive care. Although avapritinib, a highly selective KIT D816V inhibitor, has demonstrated efficacy in randomized clinical trials, real-world data in patients with ISM remain still limited.

Adult patients with ISM treated with avapritinib who were followed longitudinally at Greek National Center of Expertise for Mastocytosis were included in our study. Baseline and 6-month follow-up assessments included basal serum tryptase (BST) levels, KIT D816V variant allele frequency (VAF) in peripheral blood and Mastocytosis Activity Score (MAS). Molecular analyses were performed using digital PCR (dPCR). Clinical effectiveness, treatment dosing, dose modifications, and tolerability were recorded.

Five male patients with ISM were included; all KIT D816V-positive. All patients demonstrated a marked reduction in BST levels, with median BST decreasing from 37.1 ng/mL (range 28.5-105) at baseline to 15.3 ng/mL (range 11.8-24.7) at 6 months, corresponding to a median reduction of approximately 61%. Median baseline KIT D816V VAF was 2.1% (range 0.25–3.5%). At follow-up, KIT D816V became undetectable in two patients, while the remaining three showed marked reductions in VAF to 0.03%, 0.05% and 0.27%. Clinical improvement was reflected by a significant reduction in MAS, from a median of 38% (range 25–48%) at baseline to 16% (range 3–25%) post-treatment. Symptom improvement was consistent across multiple organ systems, including cutaneous, gastrointestinal manifestations and anaphylaxis. Four patients received avapritinib 25mg daily, while one required dose escalation to 50mg due to inadequate initial response. Avapritinib was well tolerated, with no treatment discontinuations or major adverse events reported during follow-up.

In this real-world cohort, avapritinib was associated with substantial biochemical improvement, deep molecular responses, and clinically meaningful symptom reduction in patients with ISM, with an excellent safety profile. These findings highlight the potential role of avapritinib as an effective and well-tolerated therapeutic option for ISM in routine clinical practice.