Avapritinib Offers Sustained Benefit in Indolent Systemic Mastocytosis

A study demonstrated the long-term effectiveness of avapritinib over 3 years for indolent systemic mastocytosis (ISM).1

“Avapritinib robustly reduces disease-related symptoms and achieves durable improvements in QoL after a median of ~3 years of follow-up,” wrote investigators, led by Hanneke Oude Elberink, from the Groningen Research Institute Asthma and COPD at the University of Groningen in the Netherlands.1

Approximately 1 in 5000 people have ISM, a chronic clonal mast cell disease driven by the KIT D816V mutation in 95% of cases. Patients with this disease may have debilitating cutaneous, gastrointestinal, neurological, and musculoskeletal symptoms, which may lead to life-threatening anaphylaxis.

The US Food and Drug Administration (FDA) approved daily avapritinib (AYVAKIT) 25 mg, an oral, selective KIT D816V inhibitor, for the treatment of ISM.2 The decision was based on pivotal findings from the randomized, double-blind, placebo-controlled PIONEER trial evaluating the safety and efficacy of avapritinib for ISM.

As seen during the 24-week placebo-controlled portion, patients on avapritinib had rapid, clinically meaningful improvements in ISM symptoms and quality of life.1 Avapritinib had a comparable safety profile to placebo.

The team presented a longer-term analysis of the PIONEER study at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 from June 13 – 16 at Glasgow, United Kingdom. This open-label period had up to a 5-year follow-up; data presented had a cutoff date of September 20, 2024.

During PIONEER, 226 patients began avapritinib therapy at 25 mg once daily alongside best supportive care. The sample had a mean age of 49.8 years, was mostly female (73%), and had a mean ISM symptom burden of 19.5. The median duration of follow-up was 35.3 months, about 3 years.

Long-term efficacy was assessed using the ISM-Symptom Assessment Form (ISM-SAF), designed to evaluate ISM symptomology based on the severity of 11 symptoms; total scores ranged from 0 – 110. Quality of life was measured via the Mastocytosis Quality-of-Life Questionnaire (range, 0 – 100) and the 12-item Short Form Survey (SF-12), and the Patient Global Impression of Severity (PGI-S).

Investigators conducted 3 analyses:

1. All patients on avapritinib (either 25 or 50 mg)
2. Only patients who stayed on avapritinib 25 mg (n = 169)
3. Only patients who were dose-titrated to 50 mg (n = 57)

At the 3-year follow-up, patients had durable improvements in ISM symptoms and quality of life. The mean change from baseline in Total Symptom Scores was -17.51 at week 96 and -20.07 at week 144 in all patients treated with avapritinib.1

Participants experienced sustained benefits with avapritinib, as shown by mean percentage improvements from baseline in the SF-12 scores at weeks 96 and 144. Physical component scores improved by 21.54% and 20.84%, respectively, while mental component scores improved by 10.63% and 12.70%. More than half of patients treated with avapritinib had a ≥ 1 improvement in PGI-S at week 96 (60%) and week 144 (64%).1

Avapritinib 25 mg continued to show a favorable safety profile at the 3-year follow-up. The most common adverse event was grade 1 edema (peripheral or periorbital), followed by headache, nausea, fatigue, diarrhea, alopecia, and dizziness.

There were low rates of grade ≥ 3 treatment-related adverse events. Treatment discontinuation due to treatment-related adverse events (3%).

Patients on avapritinib 50 mg were on this treatment for a median of 10.6 months (range, 0.3 – 26.8). A quarter (25%) of participants had treatment-related adverse events, with none being grade ≥ 3 or serious; the only event occurring in more than 1 patient was peripheral edema (n = 4). No patients discontinued avapritinib 50 mg due to treatment-related adverse events.1

Most patients (41 out of 44) who completed 8 weeks of avapritinib 50 mg had a stable improvement on Total Symptom Scores and Mastocytosis Quality-of-Life Questionnaire.

“Avapritinib is an effective therapeutic option for patients with ISM with a favorable long-term benefit-risk profile across the spectrum of disease,” investigators concluded.1

References

1. Elberink H, Akin C, Castells M, et al. Favorable Benefit-Risk Profile of Avapritinib in Indolent Systemic Mastocytosis Is Maintained After 3 Years of Therapy: Longer-Term Analysis of the PIONEER Study. Presented at EAACI from June 13 – 16 at Glasgow, United Kingdom.

2. FDA Approves AYVAKIT® (avapritinib) as the First and Only Treatment for Indolent Systemic Mastocytosis. Blueprint Medicines. May 22, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/fda-approves-ayvakitr-avapritinib-first-and-only-treatment. Accessed July 31, 2025.