Tiny Mutation Triggers Drug Resistance For Patients With One Type Of Leukemia

Blood sample showing chronic lymphocytic leukemia (CLL) cells (Photo: Wikipedia)

Blood sample showing chronic lymphocytic leukemia (CLL) cells (Photo: Wikipedia)

Ibrutinib is a highly-effective, precisely targeted anti-cancer drug that received accelerated approval from the Food and Drug Administration for use in chronic lymphocytic leukemia (CLL) in February. It has revolutionized treatment, transforming CLL from a deadly disease to a chronic one. But about eight percent of patients develop resistance to this lifesaving drug.

Now, a multi-institutional team of researchers, including Y. Lynn Wang, MD, PhD, professor of pathology at the University of Chicago, has pinpointed exactly what goes wrong when CLL patients develop resistance to ibrutinib. In a correspondence published online May 28 in the New England Journal of Medicine, they show how the mutation triggers resistance. Their finding could guide development of new agents to treat drug-resistant disease.

“In a way, we are repeating, at a faster pace, the story of Gleevec (imatinib), a landmark drug that transformed care for a different type of leukemia,” said Wang, the study’s senior author. “That story began with development of an effective drug with few side effects, but in many patients the leukemia eventually found a way around it after long-term use. So researchers developed second-line drugs to overcome resistance.”

The breakthrough came after Wang and one of her graduate students noticed a genetic change in one of the patients for a phase 1 clinical trial for ibrutinib. Read more about the study in our Newsroom. Medpage also posted an update on phase II and phase III trial results showing significantly improved survival rates for patients taking ibrutinib.

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