Dr Radia on 4-Year Data for Avapritinib in Advanced Systemic Mastocytosis

In terms of the overall responses for those patients [who] were [treated in the] first line, there was a very good response. [The] ORR was still 87% with 4 years of follow-up, [and] the CR, which means that a complete resolution of their mast cell disease burden, or CRh [rate] was 43%.

Deepti Radia, MBBS, BSc, MRCPI, FRCPath, MSc Med Ed, a consultant hematologist, chair of the London Specialist Training Committee, and chair of the National Specialist Advisory Committee in haematology at Guy's and St Thomas' NHS Foundation Trust, discussed 4-year data from the phase 2 PATHFINDER trial (NCT03580655) evaluating avapritinib (Ayvakit) for the treatment of patients with advanced systemic mastocytosis.

Long-term findings presented at the 2025 ASH Annual Meeting and Exposition showed that avapritinib was well tolerated and yielded durable efficacy, favorable survival outcomes, and signals of disease modification. In all patients evaluable for response (n = 83), avapritinib generated an overall response rate (ORR) of 73% (95% CI, 63%-83%), including a complete response (CR) or CR with partial hematologic recovery (CRh) rate of 30%.

Radia specifically highlighted outcomes for the use of first-line avapritinib. Among evaluable patients treated in the first-line setting (n = 30), the ORR was 87% (95% CI, 69%-96%) with a CR/CRh rate of 43%. The median durations of response were 57.8 months (95% CI, 46.1-not reached [NR]) in the overall population and NR (95% CI, 37.1-NR) in the first-line population. The median progression-free survivals were 51.3 months (95% CI, 38.7-NR) and NR (95% CI, 39.4%-NR), respectively. At a median follow-up of 49 months, the median overall survival was 62 months (95% CI, 60.0-NR) in the overall population and NR (95% CI, NR-NR) in the first-line population.

Additionally, 74% of all patients achieved clearance of bone marrow mast cell aggregates, including 84% of patients treated in the first line. Serum tryptase levels were reduced to less than 20 ng/mL in 65% of all patients and 79% of first-line patients; the respective rates of patients with a KIT D816V variant allele frequency of less than 1% were 64% and 67%. Clinical resolution of palpable spleens occurred in 78% of the overall population and 72% of the first-line population.

Radia concluded that patients who were TKI naive experienced good outcomes with avapritinib, and even with reduced doses over the course of treatment, achieved decreases in mast cell disease burden.

Avapritinib was previously approved by the FDA in June 2021 for the treatment of adult patients with advanced systemic mastocytosis, including those with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia, based on data from the phase 1 EXPLORER trial (NCT02561988).