Long-Term PIONEER Data Reinforce Avapritinib’s Benefit–Risk Profile in ISM, with Cem Akin, MD

Avapritinib continues to deliver durable symptom control and quality-of-life improvements nearly 4 years into treatment for patients with indolent systemic mastocytosis (ISM), reinforcing its role as a long-term targeted therapy for this chronic disease.1

Avapritinib was approved for treating ISM by the United States (US) Food and Drug Administration (FDA) in May 2023.2 Updated data from the Phase 2/3 PIONEER trial (NCT03731260) were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 Annual Meeting held in Philadelphia, Pennsylvania, by Cem Akin, MD, Professor of Medicine at the University of Michigan Division of Allergy and Immunology.

PIONEER saw 226 adults with moderate-to-severe ISM initiating avapritinib 25 mg once daily alongside best supportive care. As of February 21, 2025, the median treatment duration was 40.0 months (range, 0.7–67.2 months), providing 1 of the longest follow-ups to date in this population. At approximately 3.5 years, patients maintained clinically meaningful improvements in symptoms as measured by the ISM-Symptom Assessment Form, as well as sustained gains in quality of life on the Mastocytosis Quality-of-Life (MC-QoL) questionnaire.

Importantly, durability was observed across subgroups: patients who remained on 25 mg throughout treatment and those who underwent dose titration to 50 mg in Part 3 of the study (n = 65), based on investigator discretion and disease burden.

In an interview with HCPLive at AAAAI, AKin emphasized the importance of the long-term consistency of benefit for ISM, where more than 80% of patients fall into the non-advanced category and historically have relied only on symptomatic therapies such as antihistamines. Prior to avapritinib, available treatments did not meaningfully reduce mast cell burden or target the underlying KIT D816V mutation, which drives over 90% of ISM cases.

PIONEER previously demonstrated significant symptom score reductions at six months compared with placebo, along with reductions in mast cell burden parameters, forming the basis for US approval in 2023. The new long-term data extend those findings, showing that symptom control is not only sustained but in some cases appears slightly improved over time.

Equally important, the safety profile remained favorable over extended follow-up. Avapritinib was well tolerated at both 25 mg and 50 mg daily, with no new safety signals identified. Edema, most commonly periorbital or pretibial, remained the most frequently observed adverse event. Notably, no intracranial hemorrhages or cognitive adverse events were observed at these lower doses in the non-advanced population, addressing concerns raised in prior higher-dose studies in advanced disease.

“In the 4 year trial now we are extending those observations, there are some patients who are on the drug for more than 5 years, but on average, 4 year follow up, and the efficacy was sustained at the same level, maybe slightly even improved at 4 years than at 6-month and 1-year time frames,” Akin said.

Akin’s disclosures include Blueprint Medicines, Cogent, Telios, GSK, and Novartis.

References

1. Akin C, Tashi T, Elberink HO, et al. Avapritinib continues to demonstrate durable symptom control with a well-tolerated safety profile: Long-term outcomes from PIONEER. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Abstract #509

2. FDA Approves Avapritinib for the Treatment of Adult Patients with Indolent Systemic Mastocytosis. News release. ACCC. May 24, 2023. https://www.accc-cancer.org/view/fda-approves-ayvakit-(avapritinib)-for-the-treatment-of-adult-patients-with-indolent-systemic-mastocytosis-(ism)