Dr Tashi on Updated Efficacy Data for Avapritinib in Indolent Systemic Mastocytosis

“The long-term follow-up [data from the PIONEER study] show that the symptom improvement in patients is deep and sustained, even at 2 to 3 years.”

Tsewang Tashi, MD, an associate professor of internal medicine at the University of Utah, discussed the long-term efficacy data for avapritinib (Ayvakit) in patients with indolent systemic mastocytosis (SM) from part 3 of the phase 2 PIONEER trial (NCT03731260), which were presented at the 2025 ASH Annual Meeting and Exposition.

Building on data from part 2 of the trial, Tashi began by outlining differences between part 2 and 3 of the trial, the most notable being the length of follow-up. Part 2 of the trial had a 24-week follow-up, and its findings supported avapritinib’s FDA approval for advanced and indolent SM. Part 3 is an ongoing, open-label, long-term extension of the study, and its updated efficacy data reached 3 years of follow-up. Regarding efficacy data for each part of the trial, Tashi pointed out that there were many similarities. The analysis of part 3 included all patients treated with avapritinib over the 3 different parts of the study.

In updated findings from part 3, the mean total symptom score (TSS) improvements with avapritinib at 2 years (n = 164) was –17.51 points and –19.39 points for patients at 3 years (n = 127). Tashi mentioned that TSS improvements from part 3 of the trial were consistent from TSS improvement data in part 2, thus demonstrating how symptom improvements are sustained with avapritinib.

Moreover, other key efficacy data for avapritinib like quality-of-life changes remained deep at 2 and 3 years. Mean changes in quality-of-life for patients at 2 years (n = 140) were –28.73% and –34.64% at 3 years (n = 125). Furthermore, no additional safety signals were reported with longer-term follow-up at either the 25-mg or 50-mg doses.