Treatment Outcomes

Adherence to Therapy

It is important for patients to continue taking their medication to get the best response. Unless they are following their doctor’s instructions, stopping medication or taking less than the amount prescribed can impact how well the medication works and may result in a loss of response and an unfavorable treatment outcome.

For patients with CML, adhering to treatment is associated with the probability of achieving and improving long-term outcomes, including achieving a major molecular response and improved survival. Good adherence means that a patient follows all of the doctor’s recommendations, including

Taking the appropriate number of pills as ordered: at the right time, on the right day, every day
Reporting any side effects so that supportive treatment can be administered
Avoiding foods, liquids or other medications that not allowed.

Patients should let their treatment team members know if there are any problems (including side effects) that make it difficult for them to take the medication as prescribed. Generally, these difficulties can be either managed or completely overcome.

My CML Tracker Pages is a tool to help you keep track of appointments, questions for your doctor, medications, side effects, test results and notes. You may download a copy of My CML Tracker Pages.

Measuring Treatment Response

Your doctor needs to monitor your response to drug therapy for chronic myeloid leukemia (CML) with blood and bone marrow tests. This is a critically important part of treatment for people with CML.

Your test results help your doctor decide whether to:

Increase your drug dose to try for a better response
Decrease or stop the drug briefly because of side effects
Change to a different drug or drug combination to better control the CML
Change to a different drug or drug combination to manage side effects

Your doctor measures your response using general treatment response guidelines for your first year of CML drug therapy. He or she regularly measures the number of red cells, white cells, platelets and CML cells in your blood. Your doctor compares these numbers with the results of the lab test done at the start of your treatment.

Types of Response

After patients begin treatment, their doctors will periodically order blood and bone marrow tests to determine whether they are responding to treatment. A treatment response is an improvement related to the patient’s treatment. Monitoring treatment response is one of the key strategies for managing CML. In general, the greater the response to drug therapy, the longer the disease will be controlled

There are three types of responses:

Hematologic
Cytogenetic
Molecular

Treatment Response Milestones

People with CML respond to treatment in different ways. These are general guidelines for CML drug therapy. Your baseline results (your test levels at the time of diagnosis) can influence your response. But, your doctor will generally work with the following time frame as a guideline to achieve the desired response:

The International Scale (IS)

This is a standardized scale for measuring qPCR test results. The qPCR test measures the number of cells that have the BCR-ABL1 gene. It is used to determine how well treatment is working. The International Scale defines the standard baseline as BCR-ABL1 100 percent. A log reduction indicates the BCR-ABL1 level has decreased by a certain amount from the standard baseline.

1-log reduction means that the BCR-ABL1 level has decreased to 10 times below the standardized baseline. This means that 10 percent of cells (10 out of every 100 cells) have the BCR-ABL1 gene. This reduction is equivalent to an early molecular response when achieved within 3 to 6 months of starting treatment.
2-log reduction means that the BCR-ABL1 level has decreased to 100 times below the standardized baseline. This means that 1 percent of cells (1 out of every 100 cells) have the BCR-ABL1 gene.
3-log reduction means that the BCR-ABL1 level has decreased to 1,000 times below the standardized baseline. This means that 0.1 percent of cells (1 out of every 1,000 cells) have the BCR-ABL1 gene. It is also known as a “major molecular response (MMR).” { 4-log reduction means that 0.01% of cells (1 out of every 10,000 cells) have the BCR-ABL1 gene.
4.5-log reduction is referred to as a “complete molecular response (CMR)” or a “deep molecular response (DMR).” Doctors may refer to this as “MR4.5.” A 4.5-log reduction indicates that 0.0032% of cells (1 out of every 32,000 cells) have the BCR-ABL1 gene. Achieving a deep molecular response is a sign of disease remission. Patients who achieve and then sustain a deep molecular response for a significant period of time may be considered candidates for discontinuing TKI therapy, under careful medical supervision. See TreatmentFree Remission on page 34.
5-log reduction means that 0.001% of cells (1 out of every 100,000) have the BCR-ABL1 gene. By reaching a 5-log reduction, patients have achieved “undetectable BCR-ABL1.”

For patients, qPCR testing is recommended every 3 months initially. After 2 years of achieving and maintaining a BCR-ABL1 level of 0.1 percent of less, the test should be done every 3-6 months.

BCR-ABL Gene Mutation Analysis

Sometimes mutations occur in the part of the BCR-ABL1 gene that makes the BCR-ABL1 protein. These mutations alter the shape of the BCR-ABL1 protein, and this can affect how TKIs bind to the BCR-ABL1 protein to block the growth signals.

A BCR-ABL1 gene mutation analysis is a test that looks for mutations in the BCR-ABL1 gene that may cause certain TKIs to stop working. A BCR-ABL1 gene mutation test should be performed if there is

An inadequate response to initial TKI therapy
A failure to meet a treatment milestone
A loss of hematologic response, loss of cytogenetic response, 1-log increase in BCR-ABL1 levels, or a loss of major molecular response in the context of continuous therapy
Progression to accelerated or blast phase

A mutation analysis test does not need to be done in a patient who is switching medication as a result of side effects.