Fewer Severe ISM Symptoms After 4 Years of Avapritinib: Thanai Pongdee, MD

Long-term avapritinib (Ayvakit) shifted most patients with indolent systemic mastocytosis (ISM) from severe to mild symptoms through 4 years in the PIONEER study, with no new safety concerns.¹ Thanai Pongdee, MD, associate professor of medicine and research chair of the Division of Allergic Diseases at Mayo Clinic in Rochester, Minnesota, discussed the findings in an interview.

Pongdee presented the analysis at the American College of Allergy, Asthma and Immunology (ACAAI) 2026 Annual Scientific Meeting, held November 12-16, 2026, in Phoenix, Arizona, building on earlier 4-year PIONEER quality-of-life data. In the randomized portion, avapritinib 25 mg once daily reduced ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) more than placebo at week 24 (−15.6 vs −9.2 points; P = .003).² As of September 17, 2025, 226 patients had initiated avapritinib 25 mg, with a median treatment duration of 46.5 months.¹

"If your symptoms are milder, then you can fully participate in life, right? So you are not having to worry as much about what is going to happen. I can get through the school day, the work day, without being interrupted. I can be more productive. I have less stress, mental stress," Pongdee said.

The proportion of patients with severe symptoms (TSS >42) fell from 58.5% at baseline to 24.4% after 4 years, while mild symptoms (TSS <28) rose from 14.3% to 54.7%.¹ Treatment-related discontinuations occurred in 3% of patients, with edema the most common treatment-related adverse event, and Pongdee said cognitive adverse events remained infrequent. He monitors tryptase annually and may follow KIT D816V variant allele fraction to track mast cell burden.

A separate PIONEER analysis of 126 patients found similar baseline TSS regardless of lesion-affected skin surface area, with comparable gastrointestinal and neurocognitive domain scores across groups, although skin domain scores were worse with 20% or greater involvement.³ Pongdee said minimal skin disease does not rule out substantial gastrointestinal, musculoskeletal, or neurocognitive burden.

In the extension, patients with persistent symptoms could increase to 50 mg daily, an option Pongdee said the FDA label now allows after 6 months at 25 mg. The phase 4 PANORAMA-US (NCT07264959) observational study will follow about 150 adults with ISM for up to 5 years to capture symptoms, quality of life, bone health, anaphylaxis, and real-world avapritinib dosing.⁴ These congress data have not been peer reviewed.

Relevant disclosures include Blueprint Medicines.

References

1. Pongdee T, Broesby-Olsen S, George T, et al. Symptom severity reduction and QoL improvement with avapritinib in indolent systemic mastocytosis through 4 years. Ann Allergy Asthma Immunol. 2026;137:S11-S12.

2. Gotlib J, Castells M, Oude Elberink H, et al. Avapritinib versus placebo in indolent systemic mastocytosis. NEJM Evid. 2023;2(6). doi:10.1056/EVIDoa2200339

3. Broesby-Olsen S, Madigan LM, Siebenhaar F, et al. Relationship between symptoms in skin and other organ systems in indolent systemic mastocytosis. Poster R209. Presented at: ACAAI 2026 Annual Scientific Meeting; November 12-16, 2026; Phoenix, AZ.

4. Giannetti M, Duarte C, Fraser J, et al. PANORAMA-US (NCT07264959): a phase 4 observational study in indolent systemic mastocytosis. Poster R213. Presented at: ACAAI 2026 Annual Scientific Meeting; November 12-16, 2026; Phoenix, AZ.