# PIONEER: avapritinib versus placebo in indolent systemic mastocytosis

Source: https://onco.cc/key-papers/paper-pioneer-avapritinib-indolent-systemic-mastocytosis-nejm-evid-2023/  
OnCo record `paper-pioneer-avapritinib-indolent-systemic-mastocytosis-nejm-evid-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A low dose of the KIT inhibitor avapritinib eased the itching, flushing, gut and bone symptoms of indolent systemic mastocytosis more than placebo, the first drug shown to do so in a randomised trial.

## Summary

Randomised double-blind phase 2 trial of 212 patients with indolent systemic mastocytosis and moderate to severe symptoms despite best supportive care, assigned to avapritinib 25 mg daily or placebo for 24 weeks.

The total symptom score fell by 15.6 points with avapritinib against 9.2 with placebo, with parallel falls in serum tryptase, KIT D816V allele burden and bone marrow mast cells; adverse events were mostly mild. The FDA approved avapritinib for indolent systemic mastocytosis in 2023.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: NEJM Evidence
- Year: 2023
- DOI: 10.1056/EVIDoa2200339
- Authors: Gotlib J, Castells M, Elberink HO, et al.
- Findings: Total symptom score reduced by 15.6 points with avapritinib versus 9.2 with placebo at 24 weeks.; Serum tryptase, KIT D816V allele fraction and marrow mast cell burden fell with avapritinib.
- What it means: Patients with indolent systemic mastocytosis whose symptoms persist on antihistamines and mast cell stabilisers now have a disease-modifying option.
- Caveats: Symptom score is subjective and the placebo response was substantial.; Long-term safety of continuous KIT inhibition in a non-fatal disease is still being followed.

## Sources

- NEJM Evid 2023: https://doi.org/10.1056/EVIDoa2200339
- PubMed: https://pubmed.ncbi.nlm.nih.gov/38320129/

## Connected records

- cancers: [Indolent and smouldering systemic mastocytosis](https://onco.cc/cancers/indolent-systemic-mastocytosis/)
- drugs: [Avapritinib](https://onco.cc/drugs/avapritinib/)
- journals: [NEJM Evidence](https://onco.cc/journals/nejm-evidence/)

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