For CML, the target is the unique protein called the BCR-ABL tyrosine kinase enzyme. There are five drugs currently used to target tyrosine kinase enzymes for CML, called tyrosine kinase inhibitors or TKIs:imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif), and ponatinib (Iclusig).
If the leukemia does not respond to treatment, it is called refractory leukemia. Patients with this diagnosis are encouraged to talk with doctors who are experienced in treating this type of leukemia, because there can be different opinions about the best treatment plan. Learn more about getting asecond opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials. Palliative care will also be important to help relieve symptoms and side effects.
For most patients, a diagnosis of refractory leukemia is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.
The most sensitive test to look for remaining CML is called a quantitative reverse transcriptase PCR (Q-RT-PCR) test. This test is recommended every three months on a blood sample. Generally, this test can find one CML cell remaining among 1 million healthy blood cells, so, when this test is negative, it is very likely that the CML is nearly gone. On the other hand, if a person continues taking the medication as directed and the results of this test begin to rise, then the current treatment is no longer working. This means that it may be time to switch medications before the disease recurs.
Sometimes, a TKI stops working and the CML develops resistance to it. Resistance can occur if patients do not take their medication regularly, as prescribed, so it is important for patients to take their medication as prescribed. Even if patients do take the medication correctly, CML may become resistant to a TKI, which is why it is important to receive regular monitoring with cytogenetic testing, FISH, or PCR to monitor how well the drug is continuing to work.
Both dasatinib and nilotinib have been shown to bring about a complete cytogenetic response sooner and in more patients newly diagnosed with CML when compared with imatinib. However, imatinib has been used for longer. There is no difference in overall survival when using either imatinib or another one of these other drugs as initial treatment. Bosutinib and ponatinib are newer drugs but both have also produced complete cytogenetic responses in patients with CML. Because of possible severe side effects, caution and careful monitoring is needed if ponatinib is recommended after other drugs have stopped working. However, ponatinib is the only TKI that works for patients with the T315I mutation. If the medication you start with stops working, the dose may be increased or a different TKI may still be effective.