Staging Criteria for Advanced Systemic Mastocytosis Updated in the Era of KIT Inhibitors

The burden from activating KIT proto-oncogene (KIT) mutations in patients with advanced systemic mastocytosis (advSM) can be relieved with KIT inhibitors, improving the clinical trajectory of the disease. The protocols for determining staging of SM require updating since these drugs have become available, according to a review published in the International Journal of Molecular Sciences.[1]

Systemic mastocytosis is an overproduction of mast cells characterized by the accumulation of multifocal clusters of abnormal mast cells within multiple organ systems. SM is a distinct entity of myeloproliferative neoplasm, according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues.[2]

The activating KIT D816V mutations associated with SM lead to an accumulation of neoplastic mast cells in various organs causing damage that can be mitigated with KIT inhibitor therapies.

Three response criteria have been published for determining staging of the disease: Valent, Mayo, and the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis [IWG-MRT-ECNM].

The Valent criteria were based on data published in 2001. These criteria required assessment of difficult to collect patient data and did not clearly define cut-offs for response or progression. The Mayo criteria were proposed in 2010 and used predefined organ damage assessment tools. The IWG-MRT-ECNM criteria extended the Mayo criteria describing organ-by-organ specific response and progression cut-offs.

The available KIT inhibitors are imatinib, midostaurin, and avapritinib. Imatinib and midostaurin were approved for use in the treatment of advSM because they were found to induce a complete hematologic response among some patients and increased overall survival. Avapritinib is in preclinical trials currently and has been reported to be 10-fold more potent.

The challenges in updating criteria such that response to KIT inhibitors may be most accurately quantified is the combination of complex pathologic, laboratory, and clinical features that may be biased by drug effects or comorbidities.

New criteria for advSM, which used a modular approach, focusing on mast cell burden over organ damage were proposed in 2020. These criteria included pathologic response, molecular response, and clinical response.


  1. Shamali W, Gotlib J. Response criteria in advanced systemic mastocytosis: evolution in the era of KIT inhibitors. Int J Mol Sci. 2021;22(6):2983. doi:10.3390/ijms22062983
  2. Duckworth CB, Zhang L, Li S. Systemic mastocytosis with associated myeloproliferative neoplasm with t(8;19)(p12;q13.1) and abnormality of FFR1: report of a unique case. Int J Clin Exp Pathol. 2014;7(2):801-807.