Avapritinib Demonstrates Durable Improvements in Indolent Systemic Mastocytosis Symptoms, QoL

People with indolent systemic mastocytosis (ISM) receiving avapritinib 25 mg QD experienced durable improvements in disease symptoms and quality of life (QoL) through 96 weeks and tolerated the therapy well, according to updated data from the open-label extension of the PIONEER trial.1

"AYVAKIT has shown transformative clinical outcomes for patients across the spectrum of SM, including sustained disease control in ISM and prolonged survival in advanced SM. These compelling results have translated into real-world practice, with clinicians expanding their view of who is an appropriate candidate for disease-modifying therapy after positive AYVAKIT experiences, and treatment durations trending toward multiple years,” Becker Hewes, MD, Chief Medical Officer at Blueprint Medicines, said in an earlier statement.2

The median duration of avapritinib treatment was 24.4 months (range, 0.7-37.8) as of November 17, 2023, in a total of 207 patients receiving avapritinib 25 mg QD. The mean dose intensity was 24.4 mg (SD, 2.4 mg) of avapritinib per day, indicating high compliance.1

Study investigator Mariana Castells, MD, PhD, and colleagues found that patients who received 48 weeks (n = 178) and 96 weeks (n = 115) of avapritinib therapy had sustained improvements in Total Symptom Score (TSS)and all 11 individual symptom scores, including their most severe symptom, with the greatest improvements observed in spots, itching, flushing, and fatigue. The mean MC-QoL total score was 35.1 (SD, 21.4) at week 48 and 35.8 (SD, 24.2) at week 96, indicative of mild disease impact on QoL.1

The longer-term safety profile of avapritinib was consistent with previous findings with no new safety concerns. There were 6 treatment-emergent adverse events (AEs) that occurred in 99% of patients (grade ≥3 events, 39%). These were comparable to the placebo-controlled portion of the study. The rate of grade ≥3 TRAEs remained low, as did the rate of TRAEs leading to discontinuation (2%; n = 5). The most common TEAEs were edema events, which were mainly grade 1 and occurred most frequently during the first 3 to 4 months of treatment.1

Investigators found a 3% (n = 6) rate of treatment-related hair color changes was low (3%, n = 6), indicative of the selectivity of avapritinib for the KIT D816V mutation over wild-type KIT. They found that avapritinib was not associated with an increased risk of thrombocytopenia or liver injury, with 3 patients experiencing treatment-related AEs of grade 1 thrombocytopenia or decreased platelet count (1%) and 7 patients experiencing TRAEs of an increase in transaminases (3%; no grade ≥3). During the randomized placebo-controlled portion of the study, the rate of cognitive effects was similar between avapritinib and placebo; this was consistent with the incidence of treatment-related cognitive effects with longer exposure (1%, n = 3; no grade ≥3). Notably, 1 death (grade 5 AE) did occur in a patient with underlying cardiac disease who developed treatment-refractory arrhythmia during anaphylaxis; this was deemed not related to treatment by the investigator. No intracranial bleeds were reported.1

“Taken together, patients with ISM enrolled in PIONEER had poorly controlled disease-related symptoms and QoL despite best supportive care use at baseline. Patients receiving avapritinib 25 mg QD experienced durable improvements in disease symptoms and QoL through 96 weeks. The safety profile of avapritinib 25 mg QD remained favorable with longer-term follow-up. These results suggest that avapritinib, which targets the underlying driver of ISM, is an effective, well-tolerated, long-term treatment option for ISM that improves disease symptoms and QoL,” Castells and colleagues wrote.1

References

1. Castells M, Akin C, Hartmann K, et al. Continued symptom and quality of life improvement with favorable safety shown with long-term avapritinib in indolent systemic mastocytosis. J Allergy Clin Immunol Pract. 2025;13(8):2194-2196.e1. doi:10.1016/j.jaip.2025.05.026.

2. Blueprint Medicines Announces Data Reinforcing Sustained Clinical Efficacy and Well-Tolerated Safety Profile of Long-Term AYVAKIT®/AYVAKYT® (avapritinib) Treatment at 2025 EHA and EAACI Congresses. News release. Blueprint Medicines. News release. June 12, 2025. https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-data-reinforcing-sustained