Innovative Therapeutic Approaches in Systemic Mastocytosis: an Updated Review

Systemic mastocytosis (SM) is a heterogeneous clonal disorder characterized by the accumulation of abnormal mast cells in various tissues, predominantly the bone marrow. Given the rarity of the disease, the available data in Romania are extremely limited. It is estimated that the total number of diagnosed patients is approximately 170. In recent years, significant advances have been made in understanding the molecular pathogenesis of SM, leading to the development of targeted therapies that have transformed the management of this condition. The approval of tyrosine kinase inhibitors (TKIs), particularly midostaurin and avapritinib, has provided new therapeutic options for patients with advanced SM, demonstrating significant improvements in overall survival (OS) and symptom control.

To conduct a systematic review of clinical trials, observational studies and international or national guidelines published since 2000 to evaluate the efficacy, safety and mechanistic rationale of innovative therapeutic approaches for SM - including KIT inhibitors, monoclonal antibody-based therapies, stem cell transplant - and to compare the impact of these interventions with conventional cytoreductive and symptomatic treatments on overall response rate, survival, mediator-related symptom burden, quality of life and treatment-related adverse events.

A comprehensive search was performed in MEDLINE ( via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science from 1 January 2000 to 1 May 2025. ClinicalTrials.gov, WHO ICTRP. Search strings combined controlled vocabulary ( e.g. , "Mastocytosis") and free-text terms for the disease (systemic mastocytosis, advanced SM, indolent SM) with key innovative interventions (KIT inhibitors, avapritinib, midostaurin, monoclonal antibodies, stem cell transplant). No language limits were set at the search stage; non-English full texts were excluded only if an accurate translation could not be obtained. As the review relied exclusively on published or publicly available data, ethical approval and informed consent were not required.

The present review provides an updated overview of the evolving therapeutic landscape of SM, emphasizing recent clinical trial data, novel targeted therapies and emerging treatment paradigms. We discuss the implications of this progress on patient outcomes and future directions for personalized medicine in SM.