A 53-year-old male diagnosed with KIT-negative advanced systemic mastocytosis (SM) had his tryptase level decreased and his symptoms relieved after starting treatment with avapritinib (Ayvakit®).

“In our patient, the starting dose was 200 mg daily, which led to a rapid decline of tryptase level, with symptomatic improvement within months at a reduced dose of 100 mg,” said Azad et al, who reported the case in Baylor University Medical Center Proceedings.

“Treatment with avapritinib shows promising results in this difficult-to-treat condition,” they wrote.

His tryptase level decreased from 79 to 23 ng/mL with the starting dose of avapritinib and stabilized to around 50 ng/mL after dose reduction. Moreover, the patient mentioned improvement in symptoms 8 years after his diagnosis.

At clinical admission, the patient complained of a 2-year history of headache, fatigue, weight loss, memory problems, inability to fall asleep, dyspnea on exertion, abdominal pain, diffuse bone and joint pain, diarrhea, intermittent red blood in stool, and pruritic rash in the torso and extremities. He had a previous surgery for malignant melanoma.

Read more about SM experimental therapies

Biochemical analyses showed a low neutrophil count. Creatinine and liver enzymes were normal and there was no evidence of anemia, thrombocytopenia, or eosinophilia. Imaging examination showed a spleen at the upper limit of normal.

Bone marrow biopsy revealed normocellular bone marrow (50%) with trilineage hematopoiesis. In addition, it showed involvement by mast cell disease of 5%-10% of the cellular marrow, with more than 20 atypical mast cell aggregates and focal spindle cell proliferation. Immunohistochemical stains of mast cells were positive for tryptase, CD117, and CD2.

The patient’s karyotype was normal and he was negative for PDGFRA and KIT mutations. He also had no evidence of acute leukemia or a neoplasm.

With the SM diagnosis, the patient initiated treatment. Before starting avapritinib, he was treated with imatinib mesylate (Gleevec®), cladribine, nilotinib, hydroxyurea, and midostaurin but the therapy failed to reduce the tryptase level to levels below 30 ng/mL.


Azad F, Zhang J, Wang E. Avapritinib for the treatment of KIT mutation–negative systemic mastocytosis. Baylor Univ Med Cent Proc. Published online September 20, 2022. doi:10.1080/08998280.2022.2123661