News from ASH: Advances in CML Research

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CML, or chronic myelogenous leukemia, is a chronic condition, meaning patients can live with it for a long time. However, it doesn’t go away completely. Can CML be cured? Each year the American Society of Hematology (ASH) brings together experts on blood-related cancers and other conditions. On this episode of Patient Power, host Andrew Schorr broadcasts from the 50th annual ASH meeting in San Francisco. Andrew talks with Dr. Ravi Bhatia, who is co-leader of the Hematologic Malignancies Program at the City of Hope Comprehensive Cancer Center, and a specialist in treating myeloid malignancies.

Dr. Bhatia explains how the drug Gleevec has revolutionized CML treatment by reducing the bulk of the disease, although it hasn’t “cured” CML. Dr. Bhatia discusses why this may be, and host Andrew Schorr helps to make sense of all the scientific terms related to CML. Dr. Bhatia also discusses new treatments currently being researched that have the potential for curing CML. He talks about which patients are eligible for clinical trials and what to expect from a clinical trial. Finally, Dr. Bhatia explains why some patients become resistant to Gleevec and what their options are.

Because a patient’s leukemia can become resistant to certain drugs like Gleevec, Dr. Bhatia stresses the importance of being monitored by a specialist even while in remission. This webcast is a smart conversation on what you should know about CML. Listen now for an in-depth discussion on the newest treatments with an expert in the field.

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Produced in association with City of Hope

Transcript

Andrew Schorr:

Hello. This is Andrew Schorr broadcasting from the 50th annual meeting of the American Society of Hematology in San Francisco. We have been going day after day interviewing leading experts, and it is very encouraging to me that while sure we'd love to say there is a cure for this or a cure for that, we can't say that, but we can say that there is tremendous progress being made. Every year I see more and more.

Now one of the areas that we've been talking about this year is chronic myeloid or myelogenous leukemia, CML, where there are three approved medicines and others in research, and of course all of that is to truly make CML chronic, which is what the "C" is, control the disease. Wouldn't it be great if it could be cured?

Well we are going to visit now with a researcher from the City of Hope, a leading research center outside of Los Angeles to understand how we are on the trail of that to try to make that possible. My guest is Dr. Ravi Bhatia. He is a co-leader of the Hematologic Malignancies Program at the City of Hope Comprehensive Cancer Center, and he is a specialist in treating myeloid malignancies. Dr. Bhatia thanks so much for being with us.

Dr. Bhatia:

Well thank you for inviting me.

Andrew Schorr:

Dr. Bhatia so we are going to talk in a minute about the drugs that are available now because people with CML are concerned about developing a resistance to one or another and it no longer being effective, but everybody would prefer to be cured. So tell us about the work that is going on, some of the research that you are doing and some of your peers at other centers as well where maybe, maybe, maybe that could be accomplished someday.

Dr. Bhatia:

Right. Well we've been interested in understanding what effect Gleevec has on the cells that give rise to CML.

Andrew Schorr:

Gleevec of course the leading tyrosine kinase inhibitor.

Dr. Bhatia:

Right, it is also called imatinib, so forgive me if I sort of switch between the two when I talk.

Andrew Schorr:

Sure.

Dr. Bhatia:

So Gleevec has completely revolutionized the treatment of CML. I come from a center that does a lot of bone marrow transplants, and probably about eight years ago the primary treatment for CML was bone marrow transplant, and the disease responds very well to bone marrow transplant, but the problem with bone marrow transplant of course is that it's associated with a lot of toxicity, and there is a chance of dying from complications of the transplant.

The wonderful thing about Gleevec is that it is very well tolerated, and that it is very effective in getting control of the disease, and in most patients it will lead to what we call cytogenetic remission. That means that if we look for the Philadelphia chromosome, which is the hallmark of the disease, we don't find evidence of the Philadelphia chromosome on routine chromosomal testing. You can use a more sensitive test called PCR, polymerase chain reaction testing, to measure the amount of residual disease, and what we see with Gleevec is that it leads to significant reduction in the amount of residual disease down to a level less than one in a thousand, a thousand-fold reduction is achieved in the majority of patients.

Andrew Schorr:

But it's still there.

Dr. Bhatia:

But it's still there, and there are sometimes when even with these very sensitive PCR tests which can detect one in ten thousand, one in a hundred thousand cells even this test may appear to be, the test becomes negative. So you know even our most sensitive tests won't detect the disease, but the problem that we've found is that in the patients that don't have any detectable disease still are required to continue to take Gleevec in order to stay in remission. So if the drug is stopped, either for some reason of toxicity or as a trial to see if the patient needs to take the drug anymore, what happens is that there is a very high likelihood that the disease would come back when the drug is stopped.

So that suggests to us that the drug, although it really reduces the bulk of the disease, does not eliminate all the leukemia, and we think this is because it is not able to, because it has some limited ability to eliminate the cell that generates the leukemia, and this introduces the concept called an alpha leukemia stem cell, or a leukemogenic cell. So what we've learned is that just like in the normal bone marrow there is a stem cell that gives rise to all the blood cells in the bone marrow, and that is actually the cell that works in a bone marrow transplant.

Similarly in at least some leukemias, and CML is definitely one of those leukemias, there appears to be a very sort of primitive cell that gives rise to the bulk of the leukemia cells in CML, and you know we have evidence from work done in our laboratory that patients who are in remission in CML or patients who have very low levels of the disease left behind, or undetectable levels of disease left behind, still have residual leukemia stem cells.

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Page last updated on December 15, 2013