Avapritinib, a selective KIT D816V inhibitor, appears to produce rapid long-term improvement in skin symptoms among patients with advanced systemic mastocytosis (SM), according to results to be presented at the American Society of Hematology’s Annual Meeting and Exposition next month.
Advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. includes three SM subtypes: aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases. (ASM), SM with associated hematologic neoplasm (SM-AHN) and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis. (MCL). All three subtypes are predominantly driven by the KIT D816V mutation and involve infiltration of neoplastic mast cells (MCs) in various tissues. Infiltration, in turn, leads to multi-organ dysfunction and poor prognosis. Additionally, skin lesions are present in around half of patients and can significantly impair quality of life.
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Avapritinib is an oral, potent KIT D816V inhibitor approved for the treatment of advanced SM. Previous clinical trials have indicated that it significantly improves survival and increases the possibility of remission.
In this study, the authors focused on its effect on skin manifestations. The study included 34 patients who received 200 mg of avapritinib once daily.
Skin lesion burden was evaluated using artificial intelligence-based image analysis on photographs taken at multiple timepoints over 64 weeks, measuring lesion area and color changes. Additionally, patient-reported skin symptoms were assessed with the validated Advanced SM Symptom Assessment Form (AdvSMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.-SAF), focusing on itching, flushing and skin spots.
Results showed that the amount of skin impacted by lesions decreased by a median of 73% on the front torso, 76% on the back torso, 50% on the front thighs and 57% on the back thighs. Improvements were visible as early as eight weeks and lasted to the end of the study.
Furthermore, patient-reported skin severity scores improved significantly, dropping from a baseline mean of 9.6 to 3.4 at the end of the study. These subjective benefits coincided with objective reductions in disease markers, like reductions in serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. and bone marrow mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden.
“Avapritinib treatment in patients with [advanced SM] resulted in rapid reductions in affected skin lesion area and improvement in skin lesion color in the majority of patients that was sustained for more than 1 year,” the authors concluded.
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