Discussion:
Systemic mastocytosis is a rare disease which can be difficult to
diagnose and stage, as seen in this patient who experienced symptoms for
ten years before the official diagnosis was made. Although the bone
marrow biopsy performed in 2013 was negative for KIT D816V mutation,
this was likely a false negative as the assessment for that mutation was
less sensitive at the time. For patients with indolent SM, treatment
often involves symptom control. In this case, the patient was
appropriately on an antihistamine, Cromolyn, and Omalizumab to decrease
symptoms of mast cell overactivation. Despite more conservative
treatment, she was still symptomatic, and treatment with other standard
therapies for uncontrolled SM including imatinib and Midostaurin have
been limited by transaminitis. Fortunately, she was able to tolerate
Avapritinib. As of 2021 this medication has been approved by the US FDA
for treatment of advanced SM. While Avapritinib has already been
approved to treat aggressive SM, research is still being done on its use
for indolent SM. For this patient, the oral multikinase inhibitor is
highly effective against indolent SM, both in improving quality of life,
decreasing symptoms, and effectively controlling serum tryptase levels.
The dosage of 25mg daily of Avapritinib appears to be the ideal dosage
for this patient, which also happens to be the same dose that is being
studied in the PIONEER study that is investigating the safety and
efficacy of avapritinib in patients with ISM with moderate-severe
symptoms. Perhaps Avapritinib should be approved for use against the
indolent form of systemic mastocytosis and not limited to the advanced
type.