A newly-published article has outlined the key factors to help people with CML to get the most from their treatment (Baccarani and colleagues. Am Soc Clin Oncol Educ Book 2014;34:167-175; free full text at http://meetinglibrary.asco.org/content/114000167-144). This very useful advice can be summarized in four steps.
Step 1: Start treatment with a TKI (tyrosine kinase inhibitor). In many countries, five different TKIs are available: three can be used at the start, and two are kept in reserve in case they’re needed. The three starting options are Gleevec (imatinib), Sprycel (dasatinib) and Tasigna (nilotinib). Any of these medications is a reasonable treatment with which to start. All are pills that you take either once a day (Gleevec, Sprycel) or twice a day (Tasigna).
Step 2: Find the medication that you’ll be able to keep taking in the years ahead. Like all medications, each of the TKIs has a different “personality” when it comes to side effects. And each person will react somewhat differently to a drug – not just in terms of how well you respond, but how well you can tolerate side effects. It’s your job to keep your doctor informed about any problems you’re having. Sometimes a side effect will be a nuisance (such as swelling around the eyes), and sometimes they’ll be more serious (and may be detected only with laboratory tests). You may hesitate to mention a side effect if you think it isn’t important enough, but it’s best for your doctor to have the complete picture of how you’re doing.
Keeping track of how you’re reacting to a drug is important because side effects can put you off taking your medication. You may feel that the “personality” of the drug isn’t the best match for you. This can happen with any medication – some people prefer Aspirin, some prefer Tylenol – so your doctor won’t be surprised if you say that you really can’t handle the side effects of a given drug. You do have other options – but keep in mind that stopping treatment isn’t one of them. A medication can only be effective against CML if you keep taking it. TKIs suppress leukemia, but to keep the lid on the disease means you have to take your pills every day – even on the days when you don’t feel like it. Anything that stops you from taking the treatment – such as a side effect – will undermine that success. So you and your doctor need to find ways that will make it easier for you to stay on your medication. Sometimes your doctor or CML nurse can suggest tips to make a side effect less troublesome, and sometimes it will be best to consider starting another treatment.
Step 3: Have your blood tested regularly to ensure that your CML is responding to treatment. It’s essential that you and your doctor monitor your response closely. In the first 3-6 months, test results will show if you’re responding to treatment. Tests later on will still be needed to ensure that you aren’t losing the gains you’ve made.
Most people with chronic-phase CML will respond to the initial treatment. If you don’t, or if the response isn’t good enough, you will still have options. If a person doesn’t respond to the first TKI, that doesn’t mean they won’t respond to another. Your doctor will evaluate your response to a medication by obtaining a sample of your blood. These blood tests are critical because they show how much leukemia remains. The CML gene (called BCR-ABL) is a mini-manufacturing plant that produces leukemia proteins (called transcripts). TKIs suppress the number of transcripts that are produced, so measuring the transcript number is a good way to assess a drug’s effectiveness. The suppressive action of a TKI is measured in “log reductions”. Each “log” represents a factor of 10. So a 1-log reduction means the number of transcripts is reduced to one-tenth, a 2-log reduction is to a hundredth, a 3-log reduction is to a thousandth, and so on. The benchmark for success is to reduce the number of transcript to less than a thousandth (i.e. a 3-log reduction or better). This is called a major molecular response (MMR).
A blood test is needed at the start of treatment because it tells the doctor the type of leukemia transcripts that are being produced. (Some centres will obtain a sample of bone marrow as well.) But initial tests won’t show if you have responded to the medication because the drug hasn’t had time to work. So additional blood tests are needed every 3 months to ensure that you are responding to the drug. The goal is to achieve a 2-log reduction within the first six months, and a 3-log reduction (MMR) within a year. Once MMR has been reached, the frequency of blood tests can be reduced to once every 6 months.
Step 4: Take action immediately if a problem develops. If MMR isn’t reached, or if it’s reached and then you start to lose your response to the drug, your doctor will need to switch you to another medication. Regular blood tests will be your early warning system if a problem develops. A bad blood test isn’t a reason for panic. Test results can vary widely depending on the laboratory that does the analysis (and even within the same lab). So if a test result shows that the degree of control is being lost (e.g. going from a 3-log reduction to a 2.5-log reduction), it’s best to get another blood test to determine if this backsliding is a true result.
There are many reasons why someone may lose control. Not taking the medication as often as needed is one reason. Another is that a new mutation may have developed – one that enables CML to resist the effects of your TKI. Your doctor will order a mutation analysis to see if this has happened. If you have developed a mutation, you still have treatment options available to you. Both Sprycel and Tasigna have activity against a wide range of mutations. If one of these doesn’t work, you may find success with the two other drugs that have been kept in reserve – Bosulif (bosutinib) and Iclusig (ponatinib).
Fighting CML is a process of taking a medication, seeing if you can tolerate it, ensuring that it’s working, and investigating why you are no longer responding to a drug (if this happens). This step-by-step approach allows you and your doctor to fine-tune your medications, closely monitor how well you’re doing, and initiate the back-up plan if CML isn’t being controlled as well as possible. This process and the safeguards at each step will give you the best possible chance of achieving success and ensure that you get the most from your treatment.