Avapritinib improves indolent systemic mastocytosis lesions, reduces symptoms
- John Evans
- 3 hours ago
- 2 min read
Recent findings show treatment with the selective KIT D816V inhibitor avapritinib for indolent systemic mastocytosis (ISM) improved dermatologic symptoms, decreased skin lesion size, normalized skin lesion colour, and reduced skin mast cell burden.
The study was published in the Journal of the American Academy of Dermatology.
In a press release, the study’s senior author, Karin Hartmann, MD, said that her mastocytosis patients experience burning and pruritus daily, comparable to being stung by nettles.
Dr. Hartmann is an allergist and dermatologist and a research group leader in the Department of Biomedicine at the University of Basel, Switzerland.
In the release, the authors note that ISM is a clonal mast cell disease driven by the KIT D816V mutation. Symptoms can include pruritus, urticaria, brown skin lesions, anaphylaxis, abdominal pain, anemia, or weight loss, and can be debilitating.
For the study, researchers investigated the changes in the extent of the skin lesion area over 24 weeks. Patients with moderate-to-severe ISM received avapritinib 25 mg once daily (n=141) or placebo (n=71). Endpoints included skin lesion area and pigmentation, skin mast cell burden, and change in symptoms.
Investigators used artificial intelligence for the lesion size and pigmentation analysis. A subset of 111 participants had standardized photographs taken of different parts of the body.
The AI analysis was supported with specialist expertise. Dr. Hartmann and three other experienced dermatologists accompanied the process and gave feedback on the highlighted skin areas. “It was sometimes difficult for the AI to tell whether it was dealing with a mole or one of the typical brow skin lesions,” said Dr. Hartmann, in the release.
She said she felt this method, involving experienced doctors working together with artificial intelligence, is groundbreaking: “It enables a much more precise assessment,” said Dr. Hartmann.
While AI was valuable in this project, Dr. Hartmann said, it cannot replace human expertise at the moment.
“In dermatology, prospective specialists learn to look with all their senses. We also touch the skin to detect elevated lesions, for example. AI cannot do that for us yet.” However, she said it can be a valuable addition, particularly in clinical trials where precise quantification of skin lesions is important.
Image analysis showed the mean percent reduction in lesional surface area was -36.6% with avapritinib vs -1.8% with placebo in the most affected area. In the active treatment group, 86% had improved skin lesion colour, compared to 0% in the placebo group. Mean percent change in skin mast cell burden decreased with avapritinib (-22.1%) vs placebo (10.1%). Avapritinib vs placebo significantly improved the skin symptom domain score (mean change: -7.2 vs -2.8; p<.0001), including the individual skin symptoms of itching, flushing, and spots. Avapritinib was also well tolerated.