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Managing CML: Dealing With Drug Resistance

Posted Aug 24 2008 1:49pm
ANNOUNCER: Chronic Myeloid Leukemia, or CML, is a cancer of the blood where the bone marrow produces large numbers of myeloid, or white blood cells. It's a slow-growing, or "chronic," cancer that may take years to progress. Early symptoms are few, and a diagnosis of CML often catches patients by surprise.

WILLARD LANGLEY: I had my own business and I took one of those big, fancy executive exams over at Methodist Hospital and was perfect, every category except one, and that was my white blood cells. They were 19,500.

HAGOP KANTARJIAN, MD: He had what we call chronic phase CML, so he was in the very early stages of the disease.

WILLARD LANGLEY: Dr. K told me, he said, "A lot of patients have 200,000 on the white count before it's caught." So I was caught early.

ANNOUNCER: Dr. Kantarjian started Willard on what was the best treatment at the time: two medications: interferon and ARA-C.

HAGOP KANTARJIAN, MD: But the results are generally modest, and this treatment is associated with significant side effects.

WILLARD LANGLEY: It's a mean drug. It was to me. It did good for a while.

ANNOUNCER: For two years, Willard toughed it out through daily injections, flu-like side effects, fevers, extreme fatigue and a 60-pound weight loss.

WILLARD LANGLEY: I wound up in the emergency room down here with it when it got so bad.

ANNOUNCER: What's more, his CML had become resistant to the interferon and ARA-C. But by 1999, researchers at MD Anderson and elsewhere were testing a new treatment for CML, a drug that would come to be called "Gleevec."

HAGOP KANTARJIAN, MD: So I think even though he was pretty disappointed that he wasn't responding well anymore to the interferon/ARA-C, we were looking forward to putting him on this new medication and seeing how he does with it.

WILLARD LANGLEY: Dr. Kantarjian kept telling me, he said, "Hey," he said, "we've got something coming that will help you."

HAGOP KANTARJIAN, MD: We were already testing the Gleevec, and we had some inclination that it was going to work well.

WILLARD LANGLEY: And so I went on it December the 16th, and I've been told that I was the 45th patient put on it here. And then in March or April, when I got the results of my bone marrow, I was pretty close to remission. I felt a lot better.

HAGOP KANTARJIAN, MD: Within three months from starting the treatment, we achieved a complete hematologic remission. And that lasted for about two years, so he had very effective control over his disease

ANNOUNCER: The first two years on Gleevec, Willard achieved a significant response. The leukemia was affecting fewer than one in 200 of his white blood cells, but then it came back. The number of Philadelphia-positive cells, a marker for CML, had increased to 50 percent.

Dr. Kantarjian knew that one in every ten patients with early-stage CML would become resistant to Gleevec. He thought that doubling the dose of Gleevec would give Willard a second chance at remission.

HAGOP KANTARJIAN, MD: So at that point in time I talked to him about it. I talked to him about our experience where many patients who had become resistant to the regular dose of Gleevec really responded to a higher dose, when we started that.

WILLARD LANGLEY: Well, they just looked at my record and they said, "Hey, this has happened to a lot of other patients, and we have doubled their dosage, and they've done well on it, so you didn't have a choice." So I said, "Okay, I'm willing."

HAGOP KANTARJIAN, MD: We got him back to what is referred to as a partial cytogenetic response, meaning that the Philadelphia-positive cells are now under 35 percent. In fact, in his case, they are 15 percent. And that's important, because in the past, partial or complete cytogenetic response has been associated with a better survival.

WILLARD LANGLEY: My side effects increased a little bit, more swelling of the ankle, and then the eye, swelling of the eye. And that's the only side effects that I have.

HAGOP KANTARJIAN, MD: When we doubled the dose to 800, he did not experience much more of the side effects.

WILLARD LANGLEY: Dr. Kantarjian told me one day, he said, "CML is very hard to get rid of. So we may have it for a while." But, you know, as long as I have it and I feel like I do now, so you just say, "Hey, I've got CML."

HAGOP KANTARJIAN, MD: The life of patients with chronic myeloid leukemia has changed dramatically since Gleevec became available, because the drug is taken by mouth. It has very few side effects, and it controls the disease very effectively. So even if we cannot sometimes talk about the word "cure" because we cannot demonstrate elimination of the disease in all the patients, we can talk sometimes about what's called a functional cure, meaning that even though the disease is there, it's not going to affect either the quality of life or the survival of the patients.

WILLARD LANGLEY: A pretty good miracle. I have a friend that, he says, "You're the first guy I've ever known that they've developed a drug that would help you while you're still living." That makes me feel good.

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