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Understanding CML Treatment Approaches

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Published on March 24, 2014

How do a CML diagnosis and a patient's stage guide treatment? Dr. Jorge Cortes, a leading researcher from MD Anderson Cancer Center, reviews CML treatment options and explains approaches for patients who don't respond initially to treatment (primary resistance) or stop responding (secondary resistance).

Made possible through an educational grant from ARIAD Pharmaceuticals, Inc.


Transcript | Understanding CML Treatment Approaches

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

How does a CML diagnosis guide treatment options?

The first drug that we started using in this setting is imatinib, or Gleevec, a drug that specifically blocks the function of the Philadelphia chromosome, or the protein, that comes from the Philadelphia chromosome, and it is very effective.  I would say that grossly about 60 percent of patients are going to do very well with imatinib, or Gleevec.  

Then we have a second generation of drugs, called, one of them, dasatinib, or Sprycel, the other one, nilotinib, or Tasigna; and then newer ones like bosutinib, or Bosulif, and ponatinib or Iclusig.  The first two, Tasigna and Sprycel, are also approved for treatment as initial treatment for the disease, so they could be used instead of the Gleevec at the time of diagnosis.

All of these drugs are more powerful than Gleevec.  We see them work in patients even when they have not responded well, for example, to Gleevec, or when they have not been able to tolerate the Gleevec.  And in the initial therapy, we know that at least Tasigna and Sprycel work better than the Gleevec.  So we go with one of these drugs. 

And then very, very important is, number one, that the patient takes the medication every day as instructed unless there are indications that we need to do a brief stop; and number two, that we monitor the patients properly so that we know that the disease is responding the way that we want it to respond.  We want to see that there is adequate response not only by a control of the white cell count and the platelet count, etc., but most important by elimination of the Philadelphia chromosome. 

We monitor the patients and—with the different elements—and we have established what is the level of response that we need at different time points to consider that the patient has an optimal response.  And we call it optimal because we know that that predicts that the patient is likely to be well, alive and well, for many years.  We need to keep in mind that the goal in therapy in CML because we have very good treatment is that the patient lives a very long life, essentially we think that with the current treatment that the life expectancy would be very much the same as the life expectancy of anybody else of the same age, provided that we do the treatment well and without any misses. 

So, for example, we know that by three months the patient should have at least a complete hematologic response and perhaps even some cytogenetic response, meaning at least some of the cells now in the bone marrow do not have the Philadelphia chromosome.  By six months, they should have at least a major cytogenetic response—ideally a complete cytogenetic response—meaning no Philadelphia chromosome at all and a PCR of less than 1 percent optimally at six months, 10 percent at three months.  So we have these criteria that we know that are associated with the best probability of having a very good long?term outcome provided that the treatment is continued well. 

It is very important to remember that you always want to continue your monitoring, and that's throughout the therapy, and because right now the treatment is indefinite the monitoring continues indefinitely.  And certainly if there are interruptions, if the patient is perhaps not taking the medication well, etc., it's even more important. 

The way we monitor varies as the treatment evolves.  At the beginning, we want to get what we call a hematologic response, meaning we want to see that the white cell count is now normal, that the platelets are normal, etc.  So that's a control of the counts.  That's an important first step, but that's not enough. 

Then we go to what's called a cytogenetic response, and that is that in the bone marrow we do not see the Philadelphia chromosome anymore.  That's a very, very important step, because we have established that when you get to a complete cytogenetic response it predicts for an improved probability of survival—essentially a survival that's similar to an individual without leukemia of the same age. 

And then you monitor for a molecular response, that's with the PCR, which goes even deeper than the cytogenetic response and predicts that there is less of a chance of the disease ever coming back, again provided that the patient continues taking the medication.  So we want to monitor to see that these different levels of response are achieved. And even when you've achieved the molecular response, you want to continue monitoring to make sure that that remains that way. 

Now, at that stage, usually you do the monitoring perhaps every six months.  Every three to six months is considered appropriate, but it is very important to continue doing it.


Can you please help us to understand CML treatment resistance?

There is what we call the primary resistance, the patient never responded in the first place, and then the secondary resistance which is the patient responded and then lost their response.  There are many reasons why this can happen.  One of the causes of this resistance is that the cells develop what we call mutations.  That means that the protein shifts a little bit in a way that now the drug that they're receiving is not able to work anymore.  Of course, a patient can develop resistance for other reasons including not taking the medication, etc., but this is the most common mechanism. 

Fortunately, we have many drugs now available, approved by the FDA for treatment of CML, so there are second?generation medications like Tasigna, Sprycel, possibly, and then there's a third generation medication called ponatinib or Iclusig, and then there's even a drug that is not a tyrosine kinase inhibitor called omacetaxine or Synribo, which is important because probably in some patients you just need a drug that works a little different.  

So you can select these drugs based on a number of factors.  For example, if a patient has a mutation, we know that some drugs work better for certain mutations than for others, so you can select based on that.  Not everybody has a mutation, so that helps for some patients but not for all.  Then you also can look at the possible side effects.  Although these drugs are all very safe, they all have potential side effects, and many times that can help you decide what drug may be a better fit for a patient than the other. 

For example, Tasigna is more frequently associated for example, with an increase in the glucose in the blood, the blood sugar. So if you have a diabetic patient, you could consider going to another one of these drugs.  Or if you have somebody with pulmonary problems, Sprycel may have more of a chance of developing fluid around the lungs, so you may want to go with one of the other drugs. So this kind of information can help you decide which drug might be best to use for each patient. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.


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