Important Considerations

What to expect from your CML treatment.

Many patients with chronic myeloid leukemia (CML) respond to treatment with a tyrosine kinase inhibitor (TKI) for long periods of time. But over time, certain events can cause patients to lose their response. These events can include, but aren’t limited to:

How do you know what to expect from your treatment? A good place to start is understanding the tests your doctor will use to track your treatment.

Tracking your CML treatment >

Tracking Your CML Treatment

Important tests can tell you whether your treatment is getting you to your milestones.

Your doctor will use several different tests to see if your treatment is effectively moving you toward your CML milestones. It’s important to understand the schedule of these tests and the possible results—particularly in the first year or so after you have switched to a new TKI. The milestones you reach in the first 12 months and beyond of your treatment can help your healthcare teams determine the best approach to treating you.

What are the different CML monitoring tests?

To see how you’re responding to your treatment, your healthcare provider will set up a monitoring schedule that may include 3 different kinds of tests.

Learn more about CML milestones >

Type of tests my healthcare provider may run Type of response my healthcare provider is looking for What this means
Hematologic tests:
Monitoring your blood cell counts		 MaHR: Major hematologic response There are no leukemic blast cells in your blood, and your blood cell counts may be low or within the normal range
CHR: Complete hematologic response There are no leukemic blast cells in your blood, and your blood cell counts have returned to within the normal range
Chromosomal tests:
Monitoring chromosomes within your bone marrow or blood		 MCyR: Major cytogenetic response 0% to 35% of cells in the sample have the Ph chromosome
CCyR: Complete cytogenetic response No cells in the sample have the Ph chromosome
Molecular tests:
Monitoring the level of BCR-ABL transcripts in your blood		 MMR: Major molecular response The number of BCR-ABL transcripts is 1000 times less than the results from the first molecular test

Other test/response: Partial cytogenetic response (PCyR) is a response to CML treatment that indicates that between 1% and 35% of the cells in a patient’s blood or bone marrow contain the Philadelphia chromosome.

Learn more about CML milestones >

CML Milestones

How to know when it may be time for a different CML treatment.

CML milestones are important treatment goals that your doctor will expect you to reach after you start taking a tyrosine kinase inhibitor (TKI). If you take your TKI as directed, and still don’t reach a milestone, it may be a sign that your current treatment isn’t doing enough to control your CML. And that might mean it’s time for you and your doctor to talk about possibly switching to a different TKI.

A look at CML milestones.

Once you start taking a TKI, your doctor will expect you to reach several milestones within the next 12 months and beyond. Whether or not you reach these milestones will indicate how well your treatment may be working for you. The following milestones are specific to chronic phase CML:

3-to-6-month milestone

Reduced BCR-ABL transcripts

Your first treatment milestone can be reducing the amount of BCR-ABL transcripts in your blood to around 10% (or less) of pretreatment values. BCR-ABL transcripts are copies of the mutated gene that causes CML.

12-month milestone

Reduced BCR-ABL transcripts

The amount of BCR-ABL transcripts in your blood is 0.1% to less than 1%.

Beyond 12-month milestone

Major molecular response (MMR)

The amount of BCR-ABL transcripts is less than 0.1%, which is 1000 times less than the results from the first molecular test.

In your first year on a TKI and beyond, CML milestones give you and your doctor a concrete way to measure your response to your treatment. But if you’re not reaching your milestones, it may be time to consider a different treatment—and potentially time to start talking to your doctor about switching TKIs.

What if you don’t reach a milestone? >

Treatment Resistance

Several factors can impact whether your TKI helps you reach your CML milestones.

If you don’t reach a treatment milestone, it may be that you’re resistant to your TKI therapy. Resistance is defined as either an initial lack of response to a new drug or a loss of response over time. Several factors can make it more likely that you’ll experience resistance to a TKI.

BCR-ABL mutations

Mutations on the BCR-ABL oncogene (the gene that produces the BCR-ABL protein) are a common cause of TKI resistance. BCR-ABL mutations cause the shape of the BCR-ABL protein to change, preventing therapies from effectively binding.


treatment-resistance

The T315I mutation is one common BCR-ABL mutation and causes resistance to many TKIs. If your doctor thinks a mutation like T315I may be impacting your treatment, you may need mutational testing. By testing your blood or bone marrow, your doctor can tell if a mutation like T315I may be why you need to consider switching to a different TKI.

Non-BCR-ABL mechanisms

Other mechanisms of resistance that don’t affect the BCR-ABL oncogene can cause your CML to progress to accelerated phase or blast phase. They can also keep you from responding to a TKI, or cause you to lose your response over time. In both cases, these mechanisms can make it harder for you to reach your treatment milestones with many TKIs.

If your doctor has confirmed resistance, it may be an appropriate time to switch.

Typically, your healthcare provider will track your response to treatment by testing your blood or bone marrow at specific time points. These scheduled tests allow your healthcare provider to see if you’re reaching your treatment milestones. If you have not met these goals, your healthcare provider may have determined that your CML is resistant to your current treatment and it’s time to consider switching TKIs.

When it may be time to consider ICLUSIG® (ponatinib).

If your doctor has determined that no other TKIs are appropriate for your resistant CML, or that your CML is T315I-positive, your doctor may decide it’s time to consider ICLUSIG.

Talking with your doctor >

Talking with your Doctor

If your doctor has confirmed TKI resistance, working with your medical team is key.

When you’re coping with any cancer and its treatment, it’s important to have honest, open conversations with your doctor. When you have those conversations, remember: Your medical team understands the challenges of switching CML therapy, and needs to know about your questions and concerns. There is no question too minor. Ask whatever’s on your mind. Be completely straightforward about your medical history.

Think you might want a second opinion? Don’t feel guilty. It’s your absolute right. Get a referral from other patients, caregivers, patient advocates, or local patient support groups. Remember to check whether the referral is covered by your health insurance.


Helpful tips for your next doctor visit:

  • Taking notes is always a good idea. Bring a pen and paper to each visit.
  • Ask questions about anything you don’t understand.
  • Bring a friend or family member to appointments for support and a second set of ears. Encourage them to ask questions too.
  • Ask your doctor to explain which treatment milestones you should reach next.
  • Ask about available support programs for CML and cancer.
  • Most of all, stay engaged. Be a full partner in your treatment. Learn everything you can. Ask about anything you want to learn more about.