Candidates for Consideration: Who Would Benefit from Avapritinib?

Identifying Appropriate Candidates for Avapritinib Therapy in ISM

The long-term safety data from the PIONEER trial provides reassuring evidence for avapritinib's tolerability profile, with major adverse events limited to peripheral and periorbital edema. Importantly, the safety concerns observed in advanced mastocytosis trials using higher doses (200 mg) were not replicated in the indolent systemic mastocytosis (ISM) population receiving 25-mg dosing. The concerning signals from high-dose studies, including intracranial bleeding in patients with low platelet counts and neurocognitive changes, were absent in the PIONEER long-term follow-up data. This favorable safety profile supports the consideration of avapritinib for appropriate ISM patients who remain symptomatic despite standard treatments.

Patient selection requires careful evaluation of contraindications and risk factors. Absolute contraindications include platelet counts below 50,000 (as specified in FDA labeling due to intracranial bleeding risk) and pregnancy (due to teratogenic potential of tyrosine kinase inhibitors). Additional relative contraindications that many providers consider include prior history of intracranial bleeding, stroke, brain lesions, or current anticoagulant therapy, as these factors may increase bleeding risk. These exclusions help ensure that avapritinib is prescribed to patients who can safely benefit from therapy while minimizing potential complications.

Ideal candidates for avapritinib therapy are patients with chronic, moderate to severe ISM symptoms who require daily antihistamine or antimediator treatments yet continue experiencing breakthrough symptoms such as flushing, itching, and abdominal pain. The decision-making process should involve mutual discussion between health care providers and patients, particularly when standard treatments cause problematic adverse effects or drug interactions. For example, antihistamines can interfere with calcium absorption, potentially exacerbating the baseline osteoporosis risk in ISM patients. Following appropriate patient selection and shared decision-making, treatment typically begins with 25 mg dosing, with monitoring for response and potential dose escalation to 50 mg if symptoms remain inadequately controlled.