Combining CLL drugs to overcome the problem of resistance

Arnon Kater, MD, PhD of the Academic Medical Center, Amsterdam, Netherlands talks about the combination of chronic lymphocytic leukemia (CLL) drugs to overcome the problem of resistance at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Prof. Kater starts by explaining that so far, it seems that for example p53, which is a good predictor for non-responsiveness to chemotherapy, is there from the beginning. However, for BTK inhibitors, like ibrutinib, it seems that the mutation in the BTK gene is not there from the beginning. It is a novel mutation that arises by giving therapy. He explains that in different parts of the body, cells are less or more sensitive. For example, venetoclax is extremely sensitive in blood cells but is resistant in the lymph node environment. He believes that it is matter of combining drugs that actually chase the cells out of this microenvironment and then give venetoclax, which is very specific in the blood, or by giving a combined inhibitor.

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