Systemic Mastocytosis: Current Status and Challenges in 2024

Systemic mastocytosis (SM) is a rare disease and has had significant discoveries in its biology, prognostication, and management in the past two decades. The latest update of the WHO classification and the new ICC classification are current standards in the diagnosis and prognostication of SM. In clinical practice, SM can be divided into two main categories: non-advanced SM (nonAdvSM) and advanced SM (AdvSM). The integration of clinical signs and symptoms as well as bone marrow morphologic, immunophenotypic, and molecular results is required to diagnose SM variants. In the modern era, data with KIT inhibitors (i.e., avapritinib) suggest prolongation of survival in AdvSM. Although this is encouraging progress, and we now have effective drugs for managing both ISM and AdvSM patients, there are still remaining challenges in SM. For example, optimal initial treatment in certain patient subsets, such as SM with an associated hematologic neoplasm (SM-AHN), remains under debate (e.g., treatments targeting AHN or SM, monotherapy or combinations). Prospective studies evaluating drugs with different mechanisms of action are needed for such patients. This review provides an updated overview of SM, including the latest methods for diagnosis, patient classification based on their prognosis, and management according to the most significant clinical trials, covering both patients with nonadvSM and AdvSM.