Tyrosine kinase inhibitors (TKIs) are a type of targeted therapy. TKIs come as pills, taken orally. A targeted therapy identifies and attacks specific types of cancer cells while causing less damage to normal cells. In CML, TKIs target the abnormal BCR::ABL1 protein that causes uncontrolled CML cell growth and block its function, causing the CML cells to die.
The first therapy given for a disease is called “initial” or “first-line” treatment. The following four TKI drugs are approved as first-line treatment for chronic phase CML:
- Imatinib mesylate (Gleevec®)
- Dasatinib (Sprycel®)
- Nilotinib (Tasigna®)
- Bosutinib (Bosulif®)
If the first treatment does not work because of intolerance (intolerable side effects) to a particular drug or drug resistance (the CML is not responding to the drug) during therapy, a second treatment option is tried. If both the initial treatment and the subsequent treatment (second-line) fail to work, a third 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®)
Patients with a history of cardiac disease or peripheral vascular disease need to be monitored carefully and frequently during TKI treatment. Some patients treated with TKIs have developed serious cardiac side effects, including heart attacks and changes in heartbeat rhythm. Some have developed narrowing of the arteries in the extremities of the brain, which can cause a stroke. Many patients who develop these adverse effects also have other health problems and risk factors, including older age, high blood pressure, high cholesterol levels, diabetes, or a history of cardiac disease, so careful monitoring is very important.
Certain drugs, herbal supplements and even foods can affect the way TKIs work in the body. Corticosteroids, anti-seizure medication, antacids, and the herbal supplement St. John’s Wort can make some TKIs less effective. Certain antibiotics and antifungal medication and grapefruit products may increase the levels of TKIs in the blood to high, unsafe levels.
TKIs can have serious or even deadly interactions with other prescription medications, over-the-counter medications, supplements and even certain foods. Patients should always provide their doctors with a list of any medications, herbal supplements and vitamins that they are taking to be certain that it is safe to take the products with their TKIs. And it is important to ask the doctor about any foods that should be avoided.
It is important for patients to take their TKIs as prescribed by their doctor. Adherence to an oral therapy means that a patient
- Takes the correct dose of medication
- Takes the medication at the correct time
- Never misses a dose
- Never takes an extra dose
- Does not take a dose with foods, liquids, supplements or other medications that are not allowed
- Does take a dose following any additional instructions, such as taking the medication with a meal or glass of water.
In most patients, TKIs can control CML. Patients should not skip doses to try to reduce the side effects of the medication. Patients should tell their doctors about any side effects that they are experiencing. Doctors can provide supportive treatment to help patients manage these side effects.
Patients must take their medication as prescribed to get the best response. Poor adherence to the medication regimen is the main reason for inadequate response to the prescribed treatment. Patients should not stop taking their medication, nor should they take less than the amount prescribed, unless they are following their doctors’ instructions. Taking less than the amount prescribed can affect how well the medication works and may result in unfavorable treatment outcomes.
Treatment-free remission (TFR) is achieved when a patient who has discontinued TKI therapy maintains a major molecular response (MMR) and does not need to restart treatment.
Patients with CML in chronic phase who achieve and maintain a stable, deep molecular response (DMR) for at least two years are considered good candidates for TKI therapy discontinuation, under careful medical supervision.
Why Consider TFR? There are many potential advantages of treatment-free remission for patients who have CML. These may include a combination of treatment, cost, and patient-related factors. Becoming treatment-free may:
- Reduce the risk of TKI side effects and future drug interactions. Although TKIs are generally well tolerated, they do produce side effects that may affect health and quality of life
- Benefit young female patients who are considering starting a family and may need treatment-free periods
- Ease the inconvenience of taking daily medication
- Eliminate patient co-pays and insurance costs for ongoing treatment, reducing expenses for both patients and the healthcare system.
TKI Withdrawal Syndrome. After discontinuing TKI therapy, some patients might experience muscle and/or joint pain or develop a rash. Generally, the pain can be managed with over-the-counter pain medication. TKI withdrawal syndrome has been reported in about 10 to 30 percent of patients who discontinued TKI therapy.
Patient Concerns. The main anxiety that patients experience regarding stopping TKI therapy is fear of recurrence or progression of CML. Ask questions and ask for additional information. Make sure all questions are answered before making a decision.
For more information about treatment-free remission, please download or order the free fact sheet Treatment-Free Remission.
- Download or order The Leukemia & Lymphoma Society's free booklets
- For information about the drugs mentioned on this page, visit Drug Listings.