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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. In the case of resistance and/or intolerance to second-line treatments, another TKI option for treatment is ponatinib (Iclusig®). Ponatinib is also approved to treat patients with the T315I mutation.

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. These mutations alter the shape of the BCR-ABL1 protein, which can affect the blocking action of the TKI on BCR-ABL1, allowing cancer cells to grow again. Sometimes, resistance to a TKI can be stopped by increasing the dose of the drug or by switching to another type of TKI.

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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