Symposium | Advanced systemic mastocytosis therapeutic landscape: Evidence-based strategies across the disease spectrum

At the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE, the MPN Hub held a symposium, titled Advanced systemic mastocytosis: Redefining the disease, rethinking patient outcomes. During the symposium, Alessandro Vannucchi, University of Florence, Florence, IT, delivered a presentation on evidence-based treatment strategies across the disease spectrum of advanced systemic mastocytosis (AdvSM). 

Vannucchi reviews the evolving therapeutic landscape in AdvSM, highlighting considerations that influence treatment selection across disease subtypes. Vannucchi discusses historical and contemporary treatment approaches, clinical evidence for KIT-targeted therapies, evolving goals for treatment, and emerging therapeutic strategies that may further inform future clinical management. 

Key points 

• Clinical manifestations of SM reflect both mast cell mediator release and organ infiltration, with the relative contribution of each varying across disease subtypes. 
• Management strategies differ across AdvSM subtypes, including aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), mast cell leukemia (MCL), and the subset of patients without a detectable KIT D816V mutation.¹ 
  • In SM-AHN, the relative clinical burden of the SM and AHN components influence therapeutic decision-making.¹ 
• Historical treatment approaches, including non-targeted approaches such as interferon-α and cladribine, offer cytoreductive treatment options for AdvSM, although durability of response and treatment-related toxicities vary.² 
• The introduction of KIT-targeted therapies has expanded the therapeutic landscape, with available and investigational agents demonstrating differing kinase selectivity profiles (Figure 1).³ 

• Follow-up data at 4 years from the PATHFINDER (NCT03580655) study demonstrated sustained clinical responses with avapritinib across AdvSM subtypes, including treatment-naïve patients (Figure 2).⁴ 

• Reductions in bone marrow mast cell burden, serum tryptase, KIT D816V variant allele frequency, and splenomegaly have been reported with avapritinib alongside clinical responses (Figure 3).⁴ 

• Improvements in symptom burden and health-related quality of life have been reported in clinical studies evaluating KIT-targeted therapies, highlighting the importance of assessing patient-reported outcomes alongside objective measures of disease response.^5,6 
• Ongoing clinical studies are evaluating next-generation selective KIT inhibitors, including bezuclastinib, with the aim of further characterizing their clinical activity, safety, and potential role in the evolving treatment landscape.⁷ 
• The therapeutic landscape of AdvSM continues to evolve, with increasing understanding of disease biology, individualized treatment approaches, and ongoing evaluation of KIT-targeted therapies contributing to advances in disease management. 

This educational resource is independently supported by Blueprint Medicines. All content is developed by the faculty in collaboration with SES. Funders are allowed no influence.