Systemic mastocytosis: 2023 update on diagnosis and management in adults

ABSTRACT

Introduction

Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.

Areas covered

The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib.

Expert opinion

Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.

KEYWORDS:

• Systemic mastocytosis
• ICC
• tyrosine-kinase inhibitors
• avapritinib
• elenestinib
• bezuclastinib

Article highlights

• WHO and ICC have recently updated the diagnostic and classification criteria of SM, introducing few but important novelties compared to the previous edition.

• New genetic and molecular variables have allowed the implementation of prognostic evaluation tools, helping to improve the individualization of therapy.

• Updated data support efficacy of midostaurin in patients with advanced SM, but the feasibility appears to be limited by toxicity, especially gastrointestinal.

• Avapritinib provides excellent response both in treatment naïve and pre-treated patients, with a good safety profile also confirmed by real world-data.

• Elenestinib (Blu-263), bezuclastinib (CGT9486) and other novel agents are being tested in both advanced and limited stage of disease and will probably lead to a more complex treatment paradigm in the next future.

Declaration of interest

M Breccia received honoraria by Novartis, Incyte, BMS/Celgene, Pfizer, Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.