Symposium | Looking ahead: Future directions and unanswered questions in advanced systemic mastocytosis (panel discussion and Q&A)

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. The symposium closed with a panel Q&A session, chaired by Deepti H Radia, alongside faculty members Andreas Reiter, Johannes Lübke, and Alessandro Vannucchi. 

The panel explored key challenges in advanced systemic mastocytosis (AdvSM), including underdiagnosis and complexities in the management of SM with an associated hematologic neoplasm (AHN), and mast cell leukemia (MCL). They also discussed emerging combination therapies and highlighted allogeneic hematopoietic stem cell transplantation (allo-HSCT) as the only potentially curative option in AdvSM, emphasizing the importance of optimal disease control prior to transplantation.  

Key points

• Reported prevalence figures for AdvSM are likely an underestimate of the true disease burden owing to underdiagnosis.¹ 
• Bone marrow evaluation remains a key component of the diagnostic workup for AdvSM.^2,3  
  • KIT D816V mutation testing should be performed in both peripheral blood and bone marrow using highly sensitive assays (e.g. digital droplet polymerase chain reaction [PCR] or quantitative PCR), as a negative peripheral blood result does not exclude SM.^3,4 
• Treatment decisions for SM-AHN should be individualized based on several factors, including the AHN subtype and KIT D816V allele burden.^3,5 
  • SM associated with a JAK2-positive myeloproliferative neoplasm (MPN) may, in some cases, represent a more indolent disease phenotype. Where treatment is required, the AHN component may warrant greater therapeutic attention than the SM.⁶ 
  • Reassessment of both the SM and AHN components throughout treatment is important.⁵ 
  • Combining KIT inhibitors with hypomethylating agents is a rational strategy for patients with SM and acute myeloid leukemia (AML); however, it remains investigational, with safety concerns including treatment-related cytopenias.⁵ 
• Specific treatment options for MCL remain limited, and therapies used for both SM and AML have been applied with variable success.⁷ 
  • Targeted therapies, such as tyrosine kinase inhibitors aimed at KIT mutations, have shown promising results in some types of MCL, with chemotherapy reserved for MCL with aggressive AHN.⁷ 
• Allo-HSCT is the only known potentially curative treatment option for AdvSM.² 
• While targeted therapies can facilitate improved pre-transplant disease control, treatment and transplantation decisions remain highly individualized, particularly with respect to patient factors such as age and fitness.^2,3,8 

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.