Leukemia Current Topics in Leukemia

Emerging Therapies in CML

Summary & Participants

For patients with CML whose disease is not responding to imatinib, also known as Gleevec, there are other treatment options. FDA approved drugs are available for those who are intolerant or resistant to imatinib, and new therapies are currently in clinical trials.

Medically Reviewed On: December 19, 2007

Webcast Transcript

ANNOUNCER: Imatinib, also known as Gleevec, is an effective treatment for patients diagnosed in the chronic phase of CML. However, some patients cannot tolerate its side effects.

JORGE CORTES, MD: Intolerance to Gleevec, fortunately, is not a common phenomenon. And I’m talking about intolerance to the point where you really just cannot take imatinib despite dose adjustments and management, etc. It’s about 3 to 4% of the patients who really cannot take it at all.

ANNOUNCER: A small minority of patients may not respond well to imatinib from the start. This is called primary resistance. Other patients may develop secondary resistance, a relapse after a period of good control of the disease. Resistance may be caused by point mutations. Changes in the DNA lead to small changes in the BCR-ABL protein and imatinib can no longer fit in the binding site and the abnormal growth of white blood cells resumes.

JORGE CORTES, MD: Mutations occur in about 40 to 50% of patients who develop resistance. So in at least half of the patients, we don’t know what the mechanism of resistance is.

ANNOUNCER: Dasatinib, also known as Sprycel and nilotinib or Tasigna are FDA approved for patients who have become intolerant or resistant to imatinib. Like imatinib, both drugs are tyrosine kinase inhibitors.

STEPHEN NIMER, MD: Dasatinib inhibits BCR-ABL, but it also inhibits another class of kinases or enzymes in the cell and those are called SRC family kinases.

NEIL SHAH, MD: We now know with approximately 15 months of follow up that 49% of patients on the phase II chronic phase study have achieved a complete cytogenetic response on dasatinib.

ANNOUNCER: Cytogenetic testing showed no detectable disease.

STEPHEN NIMER, MD: Nilotinib is a drug that's very similar to imatinib. It does not inhibit the SRC family of kinases that dasatinib does and it does not seem to cause the same degrees of fluid accumulation as dasatinib.

NEIL SHAH, MD: There was an update of nilotinib presented at the recent ASCO meeting which showed complete cytogenetic response rates on the order of 40% in after a median of approximately 12 months of follow up.

ANNOUNCER: Dastinib and nilotinib are generally well tolerated but some patients may experience side effects.

MICHAEL MAURO, MD: Blood count suppression is also more common on newer drugs, but that’s probably more a function of a rapid treatment effect in a person who’s probably had a bit more treatment and maybe has a bit more of an abnormal marrow underneath their CML. And we don’t think that it’s a new and heavy side effect from the drugs. And also, salts and electrolytes in the blood need to be monitored, and liver and kidney function tests, as we had with imatinib.

ANNOUNCER: Some side effects are serious and should be monitored closely.

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