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Relapsed and Refractory

Some chronic myeloid leukemia (CML) patients still have leukemia cells in their bone marrow after initial treatment with a tyrosine kinase inhibitor (TKI). "Refractory" is the term used to refer to a disease that has not responded to the initial treatment. Relapse is the term used to refer to the return of a disease after a period of improvement. 

TKIs used for "initial" or first-line treatment for chronic phase CML include:

  • Imatinib mesylate (Gleevec®)
  • Dasatinib (Sprycel®)
  • Nilotinib (Tasigna®)
  • Bosutinib (Bosulif®)

The first TKI treatment a patient receives may not work because the side effects may be more severe than the patient can tolerate. Or, the first TKI treatment may not work because of drug resistance, meaning the disease does not respond to the drug. 

When an initial treatment does not work, a second treatment option is tried. If both the initial treatment and the second-line treatment fail to work, a third-line treatment option can be offered to the patient.

The following TKIs are approved for the treatment of patients who have received 2 or more TKIs or who have the T315I mutation:

  • Asciminib (Scemblix®)
  • Ponatinib (Iclusig®)

TKI Resistance 

“Drug resistance” is the term used when a disease has not responded to treatment. Drug resistance in CML occurs when cancer cells do not respond to a drug that is being used to kill or weaken the cancer. 

“Primary resistance” is the term that describes resistance to a drug that is being taken for the first time in the disease process. “Secondary resistance” occurs when cancer cells initially respond to a treatment but then stop responding.

In CML, resistance is often caused by mutations in the BCR::ABL1 gene. Sometimes, resistance to a TKI can be overcome by increasing the dosage of the drug or by switching to another type of TKI. Second-generation TKIs can be effective in treating patients with mutations that are resistant to imatinib. BCR::ABL1 kinase domain mutation analysis is a test that identifies the mutations in the BCR::ABL1 gene that are frequently responsible for TKI resistance. This information can help a doctor decide which drug to prescribe.

Other Treatment Options

Additional treatment options for patients who have resistance or intolerance to TKIs may include:

  • Omacetaxine mepesuccinate (Synribo®) 
  • Asciminib (Scemblix®)
  • Interferon
  • Allogenic stem cell transplant
  • Clinical trial

For information about the drugs listed on this page, visit Drug Listings.

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