Pankit Vachhani, MD - Avapritinib versus Placebo in Indolent Systemic Mastocytosis

The study assessed the effectiveness of avapritinib, an inhibitor of the KIT D816V mutation, compared to placebo in treating indolent systemic mastocytosis (ISM), demonstrating that avapritinib significantly reduced symptoms and mast-cell burden in patients with ISM over 24 weeks.


Interview with Pankit Vachhani, MD Hematology Oncology- UAB Medicine


0:00:09 What is the objective of this study on indolent systemic mastocytosis (ISM)?
0:00:50 How were patients with ISM randomized in this study, and what were the treatment groups?
0:01:48 What was the primary endpoint measured in this study, and how was it assessed?
0:02:20 What were the secondary endpoints evaluated in this study?
0:03:19 What were the results regarding the mean change in total symptom score (TSS) between the avapritinib and placebo groups?
0:04:17 How did avapritinib treatment impact serum tryptase levels in patients with ISM?
0:05:02 Were there any notable differences in adverse events between the avapritinib and placebo groups?
0:05:59 What were the overall conclusions drawn from this trial regarding the efficacy of avapritinib in treating ISM symptoms and mast-cell burden?
0:06:56 Are there any ongoing trials or research focusing on the long-term safety and efficacy of avapritinib for patients with ISM?

The study aimed to evaluate the efficacy and safety of avapritinib, an inhibitor of the KIT D816V mutation, in treating indolent systemic mastocytosis (ISM). ISM is a clonal mast-cell disease characterized by symptoms caused by the excessive accumulation and activation of mast cells. The trial involved randomized patients with moderate to severe ISM, comparing avapritinib (25 mg once daily) to a placebo, both administered alongside best supportive care. The primary endpoint was the change in the total symptom score (TSS) based on the patient-reported severity of 11 symptoms over a 14-day period. Secondary endpoints included reductions in serum tryptase and blood KIT D816V variant allele fraction, reduction in bone marrow mast cells, and quality of life measures.

Results showed that over 24 weeks, patients treated with avapritinib experienced a significantly greater reduction in TSS (15.6 points decrease) compared to the placebo group (9.2 points decrease). Moreover, a higher proportion of avapritinib-treated patients achieved a ≥50% reduction in serum tryptase levels (54% vs. 0% in the placebo group). Adverse events included edema and elevated alkaline phosphatase, which were more frequent with avapritinib but led to few treatment discontinuations. The trial demonstrated that avapritinib was superior to placebo in reducing symptoms and mast-cell burden in patients with ISM, with ongoing investigations into its long-term safety and efficacy.