Optimizing ISM Treatment Beyond Approval, with Vito Sabato, MBBS

Mastocytosis is a rare disorder, which only received an approval of a disease-modifying therapy in 2021 with the approval of avapritinib (Ayvakit) for advanced systemic mastocytosis. Avapritinib’s approval was later expanded to include indolent systemic mastocytosis (ISM) in 2023.¹

Research continues in the field to evaluate the long-term efficacy of avapritinib and to evaluate the best treatment strategies with the therapy. Vito Sabato, MBBS, Associate professor at University of Antwerp in Belgium, presented biomarker data in patients with ISM from a proteomic analysis of PIONEER (NCT03731260), a pivotal study of avapritinib, at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California.²

HCPLive® spoke with Sabato to learn more about the findings from the PIONEER analysis as well as a post-hoc analysis of the PROSPECTOR study that used more sensitive tests to identify KIT D816V prevalence.³ Sabato also shared his excitement about the recent progress in research in the ISM field, and the continuing trajectory of research. Lastly, he also noted that overestimating the risk of anaphylaxis in patients with ISM may increase their perceived disease burden, as recent research does report a low frequency of anaphylaxis.

“What’s happened in terms of clinical research in mast cells in the last 3, 5 years hasn't happened in the last 20 years. I mean, the progress that has been made in ISM is really high,” Sabato said. “There are a lot of studies also in mast cell associated disorders that are quite frequent when compared to mastocytosis. But you know, what we can learn from the non-mutated mast cells, maybe we can still apply to the mutated mast cells. So, we are quite excited about that. And of course, we are happy for our patients.”

Sabato's disclosures include Blueprint Medicines Corporation, Novartis, and Cogent.

REFERENCES

1. FDA Approves AYVAKIT® (avapritinib) as the First and Only Treatment for Indolent Systemic Mastocytosis. News release. Blueprint Medicines. May 22, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/fda-approves-ayvakitr-avapritinib-first-and-only-treatment

2. Sabato V, Panse J, George T, et al. Multiple Proteins Correlate With Tryptase Levels in Patients With Indolent Systemic Mastocytosis (ISM): Preliminary Results of Plasma Proteomic Analysis in PIONEER. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 518

3. Hartmann K, Livideanu CB, Alvarez-Twose I, et al. Identification of Clonal Mast Cell Disease in Patients With Anaphylaxis or Evidence of Systemic Mast Cell Activation: A Post Hoc Analysis From PROSPECTOR. Abstract 301