Symposium | Advanced systemic mastocytosis: Clinical challenges and unmet needs

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, Andreas Reiter, University Hospital Mannheim, Mannheim, DE, delivered a presentation on clinical challenges and unmet needs in advanced systemic mastocytosis (AdvSM).

In this presentation, Reiter discusses how genetic complexity underpins disease heterogeneity and clinical presentation in AdvSM, how variable disease presentation can lead to diagnostic delays, and that treatment outcomes highlight variability across AdvSM subtypes. He explores the limitations of conventional disease burden assessment, the variable symptom burden impacts on quality of life (QoL) across systemic mastocytosis (SM) subtypes, and how disease heterogeneity can lead to complexity in AdvSM management. In addition, he discusses the variability in morphology and genetics in SM with an associated hematologic neoplasm (SM-AHN) and illustrates potential challenges in clinical practice using a patient case study.

Key points 

• AdvSM is driven not only by KIT D816V, but by multilineage involvement and accumulation of additional somatic mutations that can influence disease behavior and prognosis.¹ 
• ~90% of patients with AdvSM have additional somatic mutations beyond KIT D816V.¹ 
• Multilineage mutations have been associated with significantly inferior overall survival.¹ 
• There is variability in morphology and genetics in AdvSM, including variability in mast cell burden, KIT D816V burden, and AHN involvement, as observed in SM-chronic myelomonocytic leukemia (Figure 1).¹ 

• Bone marrow mast cell infiltration and serum tryptase reflect mast cell burden but do not fully capture overall disease burden, which is also influenced by KIT D816V allele burden and additional somatic mutations.¹ 
• Patterns of organ damage, cytopenias, and symptoms vary widely between patients with AdvSM, and this heterogeneity affects clinical presentation, diagnosis, treatment decisions, and the patient experience.^1-3  
• AdvSM is rare and frequently underrecognized, contributing to delayed diagnosis and missed recognition of both SM and AHN components. Variable disease presentation can contribute to diagnostic delays.^2,3  
• There are limitations to conventional disease burden assessment. It cannot be fully captured by a single biomarker and requires integrated clinical and molecular assessment (Figure 2).^3,4 

• Heterogeneity results in variable symptom burden impacts on QoL across SM subtypes, with symptom burden affecting patients across multiple domains (Figure 3).^3,4 
• The symptom burden impacts on QoL can be significant, with studies indicating that ~50% of patients with SM that may reduce their working hours and ~60% that may avoid leaving home because of their symptoms.^3,4 

• Treatment outcomes highlight variability across AdvSM subtypes, with subtype biology underlying the wide variability in clinical outcomes.^5,6 
• Survival outcomes with midostaurin vary across subtypes, with the poorest outcomes in SM-AHN and mast cell leukemia.⁵ 
• Selective KIT inhibitors improve outcomes, but treatment responses are higher in treatment-naïve cohorts.^5,6 
• Targeted KIT inhibitors such as midostaurin and avapritinib have shifted the treatment paradigm, but gaps may remain between molecular clearance and symptom relief, timing of treatment, and sequencing. As the treatment landscape evolves, the timing of intervention may be critical.^5,6  
• Overall, heterogeneity leads to complexity in AdvSM management; individualized and complex management strategies are needed, which require integration of symptom control, organ-directed therapy, molecular risk stratification, and multidisciplinary care (Figure 4).^1,4 

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.