Blood Podcast

CH in children with SCD and Asciminib for CML in the ASC4FIRST trial

Mar 26, 2026
Alexander Bick, physician-scientist studying clonal hematopoiesis in sickle cell disease. Jorge Cortes, cancer center director researching chronic myeloid leukemia therapies. They discuss asciminib's novel mechanism, superior efficacy and safety in newly diagnosed CML, and treatment-free remission goals. They also explore an unexpected higher prevalence of micro-clonal hematopoiesis in children with sickle cell disease and its distinct dynamics.
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INSIGHT

Asciminib Has A Unique Allosteric Mechanism

  • Asciminib offers a unique mechanism targeting the ABL myristoyl pocket and may reduce off-target toxicity compared with conventional TKIs.
  • Jorge Cortes notes asciminib's distinct allosteric action showed high potency in prior resistant cases including T315I, motivating its frontline testing.
INSIGHT

Deep Molecular Response And Long-Term Tolerability Matter

  • The trial prioritized deeper molecular responses and long-term tolerability as surrogates for eventual treatment-free remission.
  • Jorge Cortes emphasized monitoring deep molecular responses durability and late toxicities like cardiovascular events beyond the first year.
INSIGHT

Different Resistance Signatures After Asciminib Versus TKIs

  • Resistance patterns differed by drug: asciminib-resistant patients mainly had myristoyl pocket mutations, which still respond to conventional TKIs.
  • Cortes reported conventional-TKI resistance often lacked mutations, indicating heterogeneous resistance mechanisms.
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