Info

🌱 來自: chronic myelogenous leukemia (CML)

treatment of chronic myelogenous leukemia (CML) 

(Lancet 2015;385:1447; Hematol Oncol Clin North Am2017;31:577)

HMA: azacitidine or decitabine

Tyrosine kinase inhibitors (TKI)

❌ abl kinase activity.

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• 1st gen:

  • imatinib, 1st TKI against BCR-ABL1 (NEJM 2017;376:917)
  • 400mg daily may 800mg

• 2nd gen:

  • nilotinib, dasatinib, bosutinib.
  • consider if high Sokal score, ↑ response but ↑ toxicity.
  • No survival difference.

• 3rd gen:

  • ponatinib;
  • a/w ↓ risk of disease progress of treatment of chronic myelogenous leukemia (CML)
  • preferred for int-high risk,
  • but ↑ toxicity

ASCEND-CML

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• Imatinib, dasatinib, nilotinib, & bosutinib approved for 1st line Rx.
• Nilotinib, dasatinib, bosutinib, ponatinib, & asciminib approved for resistant disease;
• only ponatinib & asciminib effective on T315I mutation (NEJM 2012;367:2075, Blood 2021;138:2031).

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• STAMP (allosteric inhibitor): asciminib (NEJM 2019;381:2315); after ≥2 prior TKIs

• Resistance: due to ↑ BCR-ABL1 expression, often 2/2 ABL kinase mutation or amplification

• Side effects of tyrosine kinase inhibitor

• TKI discontinuation:

• Consider allogeneic HSCT for AP and BP.

• CML in pregnancy: hydroxyurea & all TKIs contraind. If Rx needed, IFN (only option).

• Milestones of Therapy of treatment of chronic myelogenous leukemia (CML)