CML Session Summaries from EHA2026 Congress - Day 2

June 2026 - We're bringing you highlights from the EHA2026 Congress with summaries of selected scientific sessions on CML.

Specialized Working Group Session: Blast Phase CML

 Chair: Andreas Hochhaus (Jena)

This Specialized Working Group session focused on one of the major remaining challenges in CML: blast phase disease. Despite the success of tyrosine kinase inhibitors in chronic phase CML, outcomes after progression remain poor. Presentations highlighted learnings from international registries, the role of genomic abnormalities in predicting disease progression, and innovative patient-derived xenograft models that may enable more individualised therapeutic approaches. A recurring message throughout the session was that preventing blast phase through improved risk stratification is just as important as developing better therapies for patients who progress.

Our key takeaways from the presentations:

Presentation 1:

Blast crisis: Lessons from real-world registries

Speaker: Kendra Sweet (Tampa)

“Overall survival remains extremely poor in this disease, and we have a lot of work in front of us if we want to improve long-term outcomes.” – Kendra Sweet

Key points:

• Poor outcomes persist despite modern therapies:
  Across the ELN, H. Jean Khoury Cure CML Consortium and MD Anderson registries, median overall survival for patients in blast phase remained only 12–24 months. Outcomes were particularly poor for patients progressing from chronic phase, emphasising that blast phase CML remains a major unmet need.
• Substantial biological heterogeneity complicates treatment:
  Blast phase CML is highly heterogeneous with regard to phenotype, prior treatment history and molecular characteristics. No standard chemotherapy regimen or preferred TKI has emerged from registry data.
• Allogeneic transplantation remains the most important treatment strategy:
  AlloSCT resulted in deeper molecular responses and improved overall survival and should be pursued whenever possible in patients who achieve a second chronic phase. Post-transplant maintenance strategies remain an area of ongoing investigation.
• The need for intensive chemotherapy remains uncertain:
  Data is conflicting on the need for chemotherapy plus TKI versus TKI monotherapy. Registry analyses suggested that the benefit of adding chemotherapy to TKI therapy may be less important in patients who subsequently undergo allogeneic transplantation. 
• Validated prognostic models can identify high-risk patients:
  The ELN blast phase prognostic score, incorporating age, blast percentage, platelet count, phenotype, extramedullary disease and de novo versus transformed disease, successfully stratified patients according to outcome and has now been independently validated.
• Collaborative studies and clinical trials are urgently needed:
  Larger international datasets and prospective clinical trials will be essential to determine optimal treatment strategies and develop more effective therapies for blast phase disease.
   

Presentation 2:

Somatic mutations and chromosomal aberrations as predictors of blast crisis

Speaker: Thomas Ernst (Jena)

“Genomic profiling may improve risk stratification, enable early identification of high-risk patients, and guide future targeted and combination therapies.” – Thomas Ernst

Key points:

• Genomic abnormalities are present from diagnosis:
  Mutations and cytogenetic abnormalities can be detected already at diagnosis and provide important information on disease biology and long-term clinical outcomes.
• Accumulation of genetic lesions drives progression to blast phase:
  Increasing genomic complexity is strongly associated with disease evolution and transformation. Additional mutations and chromosomal abnormalities accumulate during progression and appear to be major mediators of blast crisis development.
• Specific cytogenetic abnormalities identify high-risk disease:
  High-risk additional chromosomal abnormalities include 3q26.2 rearrangements, 
  11q23 abnormalities, chromosome 7 abnormalities, isochromosome 17q and complex karyotypes. These lesions are associated with inferior survival whether present at diagnosis or acquired later.
• ASXL1 and other recurrent mutations are associated with adverse outcomes:
  Mutations involving ASXL1, TP53, RUNX1 and IKZF1 emerged as particularly important high-risk lesions. ASXL1 mutations were associated with inferior molecular responses and outcomes comparable to those seen with complex karyotypes.
• Combination therapies may overcome adverse genomic features:
  Early results from the German FASCINATION study suggest that asciminib-based combination approaches may mitigate the negative prognostic impact of ASXL1 mutations and improve molecular responses.
• Genomic profiling may enable precision medicine approaches:
  Incorporating genetic information into routine risk assessment could improve early identification of high-risk patients and guide individualised treatment strategies, including targeted combinations and risk-adapted therapy.
   

Presentation 3:

PDX models to predict response to drug combinations in blast crisis

Speaker: Adam Laznicka (Prague)

“The heterogeneity observed between PDX models underlines the necessity of personalised therapeutic approaches.” – Adam Laznicka

Key points: 

• Patient-derived xenograft (PDX) models capture the complexity of blast phase CML:
  PDX models preserve clonal diversity and biological heterogeneity, allowing a more accurate representation of human blast phase disease and improving prediction of treatment response.
• PDX models can identify effective therapeutic combinations:
  Multiple models demonstrated activity of novel drug combinations, even in highly resistant disease, supporting their use as a platform for translational research.
• Marked heterogeneity supports personalised treatment approaches:
  Different models exhibited distinct resistance mechanisms and therapeutic sensitivities, emphasising that individualised treatment strategies will likely be required for blast phase CML.
• Ponatinib-based combinations showed consistent activity:
  Across several models, combinations involving ponatinib with venetoclax or ponatinib with asciminib prolonged mouse survival and overcame resistance observed with single-agent therapy. These findings provide a rationale for prioritising these combinations in future clinical studies.
• Resistance mechanisms are influenced by co-occurring mutations:
  Mutations such as NRAS affected sensitivity to venetoclax, illustrating how genomic context may influence response and highlighting the need for biologically informed treatment selection.
• Further clinical studies are required to optimise therapy:
  Additional trials are needed to determine the optimal drug combinations, dosing schedules and treatment sequences to improve outcomes for patients with blast phase CML.