Symposium | Advanced systemic mastocytosis: Diagnosis, risk stratification, and response assessment in 2026

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, Johannes Lübke, University Hospital Mannheim, Mannheim, DE, delivered a presentation on diagnosis, risk stratification, and response assessment in advanced systemic mastocytosis (AdvSM). 

Lübke discusses the current diagnostic framework for systemic mastocytosis, emphasizing the need for integrated disease assessment beyond established diagnostic criteria. Lübke explores the role of molecular profiling in prognostic risk stratification, evolving prognostic models in the era of KIT-targeted therapy, current and emerging approaches to response assessment, and the complementary role of patient-reported outcomes in evaluating disease burden and treatment benefit. 

Key points 

• Diagnosis of systemic mastocytosis is based on established World Health Organization (WHO) and International Consensus Classification (ICC) major and minor criteria incorporating morphologic, immunophenotypic, molecular, and biochemical findings.¹ 
• Following diagnosis, disease subtyping distinguishes indolent from AdvSM based on mast cell burden, associated hematologic neoplasms, and the presence of B- and C-findings (Figure 1).¹  

• Established diagnostic criteria provide the framework for diagnosis; however, serum tryptase, KIT D816V allele burden, mast cell infiltration, organ involvement, and symptom burden do not always correlate with each other or specific subtypes.¹ 
• Integrated clinical, pathological, and molecular assessment is therefore required to accurately characterize disease burden and inform management strategies.  
• Baseline molecular profiling demonstrated that >90% of patients with AdvSM treated with avapritinib harbored at least one additional somatic mutation beyond KIT D816V.² 
• Mutations in SETBP1, RUNX1, and SRSF2 were associated with inferior overall survival, supporting incorporation of molecular profiling into prognostic assessment (Figure 2).² 

• Contemporary prognostic models are evolving beyond categorical clinical variables to better reflect the molecular complexity of AdvSM, with the emerging revised Mutation-Adjusted Risk Score (MARS-R) incorporating continuous clinical and molecular parameters to support individualized risk stratification. (Figure 3).^3–9   

• High-sensitivity peripheral blood and bone marrow KIT D816V testing enables quantification of disease burden and complements response assessment by monitoring molecular response and residual disease during therapy (Figure 4).^10–13  

• Although mIWG-MRT-ECNM criteria standardize response assessment in clinical trials, complementary molecular biomarkers may provide a more practical approach to monitoring treatment response in routine clinical practice.^11,12 
• Patient-reported outcomes complement laboratory and organ-based assessments by capturing symptom burden, quality of life, functional impairment, and treatment benefit.¹³ 
• In the TouchStone survey, 93% of patients reported ≥10 symptoms, 64% avoided leaving home, and 54% reduced working hours because of disease burden (Figure 5).¹³ 

• Diagnosis, prognostic assessment, and response evaluation in AdvSM require integration of clinical, molecular, pathological, and patient-reported measures to support individualized patient 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.