Introduction: Advanced systemic mastocytosis is a rare myeloproliferative disorder of mast cells, damaging the function of various organs and tissues. The diagnosis can be challenging due to its protean manifestations and rareness. Treatment options have improved over the last years. Currently, avapritinib, a novel tyrosine kinase inhibitor with activity against p.D816V mutated KIT, is under investigation.

Case: We report a case of a 64-year old man with chronic diarrhoea, fatigue, weight loss and ascites with hepatomegaly, developing an upper gastro-intestinal bleeding with multiple duodenal ulcers. Diagnostic work-up revealed hepatosplenomegaly and portal hypertension, a vertebral compression fracture and multiple 18F-FDG avid supra- and infradiaphragmatic lymph nodes and bone marrow. Based on the 2016 WHO criteria of systemic mastocytosis, and a concomitant chronic myelomonocytic leukaemia, the diagnosis of an aggressive systemic mastocytosis with an associated haematological neoplasm was made. The patient was consecutively treated with midostaurin, cladribine and avapritinib, the latter inducing a complete biochemical and molecular response.

Conclusion: This case illustrates the challenging clinical presentation of systemic mastocytosis. A deep response to avapritinib was observed despite prior use of midostaurin and cladribine, underlining its promise in advanced systemic mastocytosis.

(BELG J HEMATOL 2022;13(2):84–91)