CML Highlights of ASH 2025

Biological overview

Expert

Associate Professor Kateřina Machová Poláková
1st Medical Faculty, Charles University 
Head, Department of Molecular Genetics and the Biobank, 
Institute of Haematology and Blood Transfusion in Prague (Czechia)

Program

Overview of significant biological aspects presented during the meeting, including:

1. Exploration of somatic mutations in CML (02:36)

• Somatic mutations at diagnosis in patients with CP-CML receiving frontline imatinib are associated with a higher rate of treatment failure: First analysis from the International CML Foundation (iCMLf) Genomics Alliance on the HARMONY platform (02:36)
• Distinct patterns of mutant ASXL1 over time and their implications for treatment failure and BCR::ABL1 mutation development in newly diagnosed patients with CML-CP treated with asciminib vs investigator-selected tyrosine kinase inhibitors in the ASC4FIRST study (04:36)
• Molecular landscape and clonal evolution in minor versus major BCR::ABL1 CML under tyrosine kinase inhibition: A study from the French group Fi-LMC (07:08)

2. TFR prediction: from bulk to single-cell analysis (10:13)

• DNA-based MRD monitoring enhances risk stratification during TKI dose reduction in CML: Evidence from a clinical trial (11:47)
• A machine-learning approach identifies a transcriptomic signature predicting treatment-free remission in CML (13:43)
• Single-cell analysis of chronic myeloid leukemia bone marrow at the time of TKI discontinuation reveals stem-cell alterations associated with recurrence versus treatment-free remission (15:35)
• A single-cell atlas of diagnostic bone marrow to uncover the origins of CML relapse following therapy cessation (17:28)

3. Questions and Answers (Clinical and Biological) (21:58)

Clinical overview

Expert

Professor Ehab Atallah
Professor of Medicine and Section Head of Hematologic Malignancies,
Medical College of Wisconsin (USA)
 

Program

Overview of significant clinical aspects presented during the conference, including:

1. New tyrosine kinase inhibitors to improve outcome

• Allosteric myristoyl pocket inhibitors
  • CARDINAL: A Phase 1 study of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor for patients with previously treated CML (03:47)
  • Efficacy of TGRX-678, a potent BCR::ABL1 allosteric inhibitor, in CML-CP and CML-AP patients harboring T315I mutation: Results from a phase 1 study (06:15)
• ATP pocket binding inhibitors (3rd generation)
  • Olverembatinib (HQP1351) demonstrates efficacy vs. best available therapy in patients with TKI-resistant CP-CML in a registrational randomized Phase 2 trial: Up to 4-year follow-up including patients without T315I mutations (07:59)

2. Combination therapy 

• Improved long-term tolerability and efficacy of asciminib-based combination therapies in newly diagnosed CML patients - the FASCINATION trial (09:21)
• ALERT CML: Asciminib as Initial Therapy with Addition of Lower Dose TKI's for Patients with CML who do not achieve DMR (11:40)

3. Dose increase for better outcome

• Asciminib in CP-CML: Efficacy and safety results of the Phase 2 ASC2ESCALATE trial in the cohort of patients with 1 prior TKI (12:34)

4. Real-world evidence in advanced phase:

• Management and outcomes of patients diagnosed with CML in blast phase: A multicenter analysis by the J Jean Khoury Cure CML Consortium (14:47)

5. ASH 2025 CML Blitz (16:34)