Avapritinib’s Effect Durable in Indolent Systemic Mastocytosis

Long-term data from the PIONEER trial, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, support the durability of response with the KIT inhibitor avapritinib (Ayvakit) for indolent systemic mastocytosis.

In this exclusive MedPage Today video, Tsewang Tashi, MD, of the University of Utah Huntsman Cancer Institute in Salt Lake City, discusses symptom improvement at 2 and 3 years, safety, and the potential for dose escalation in patients with higher symptom burden.

Following is a transcript of his remarks:

The PIONEER study was a phase II study of avapritinib versus placebo. It was a randomized study in patients with indolent systemic mastocytosis.

So this is actually the first KIT inhibitor drug that was trialed in the indolent systemic mastocytosis field. It’s a study where the primary endpoint was total symptom score improvement in these indolent systemic mastocytosis patients.

When the patients came on the study, they were blinded to either placebo or avapritinib for the first 24 weeks. And that was the primary endpoint at the end of 24 weeks. And that showed that avapritinib had a symptom improvement of 15.6 points as opposed to 9.2 points on the placebo. And based on that, it was approved by the FDA as the first drug in indolent mastocytosis in May of 2023. Since then, avapritinib has been available commercially. And the patients on PIONEER were continued on the trial up until recent times, until they hit the 5-year mark.

So patients are still on [the trial]. Many of them are now coming off study as they hit their 5-year mark. And recently, this December 2025, we had the data for the long-term outcome of these patients on avapritinib on this PIONEER trial.

So we had 2-year and 3-year data, and 2-year and 3-year data show that at 2 years the symptom improvement was sustained at 17.5 points, and at 3 years it was 19.3 points. So you can see that this symptom improvement is sustained and deeper as it goes over time. So it does indicate that avapritinib does induce, sustain, a deeper response over time.

And as far as safety’s concerned, it was very safe. There was no grade 3 or 4 significant toxicities noted. All the toxicities that were noted were very similar to the ones noted at 24 weeks. And many of these side effects — headaches, fatigue, diarrhea, and all — were very similar to the placebo group.

So the only significant side effect I would say associated with avapritinib that stands out is probably the peripheral edema — that was a little more prominent in the treatment arm.

Majority of the patients at the 2- and 3-year mark remained on the 25-mg dose. That was the chosen dose for the indolent [systemic mastocytosis]. However, there were about a little more than a quarter of patients, about 29-30% of the patients who did increase up to 50 mg of avapritinib. And the median time to this increase was about 2 years. Even when you increase the dose up to 50 mg, these patients responded very well. They did not have any new safety signals. The side effects were very similar to the 25 mg. And when you went back and looked at the subgroup of patients who had increased up to 50 mg, looking back, it seems like they had a slightly higher symptom score at baseline and maybe a little bit higher KIT very early frequency at baseline.

So right now in the real world, 25 mg is the starting dose that is labeled by the FDA, but 50 mg is also an option for patients who do not respond adequately to 25 [mg] or who may have a little higher burden of disease. So far, I think the data shows that avapritinib is very safe, very effective, and induces sustained and deep responses over time.

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