ASH 2015: Dr. Wiestner on Clonal Evolution in CLL Patients on Ibrutinib

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In the first of a two part interview from ASH 2015, Dr. Adrian Wiestner of the NIH discussed clonal evolution in chronic lymphocytic leukemia (CLL), in particular in patients on ibrutinib. These will be the final interviews to be published from ASH 2015

Take Away Points

• Ibrutinib works very well for patients who have lost P53 and who wouldn’t benefit from traditional chemotherapy.
• Following treatment with FCR, it is well known that the size of the clone that has lost P53 increases. This makes sense because that clone has a proven survival advantage in this therapeutic setting because it confers resistance to chemotherapy.
• In contrast, there is no consistent growth in the missing P53 clone after treatment with ibrutinib, perhaps because P53 itself does not confer any survival advantage with ibrutinib.
• There are, however, newly-discovered clones in the BTK pathway that do confer resistant to ibrutinib, but they start off very small and may be present for more than a year before there is evidence of clinical resistance.
• What that means is the ibrutinib is still working on some 99% of the cancer cells and shouldn’t be stopped just because a resistant clone emerges.

The basic research that Dr. Wiestner is doing for the CLL community is helping us better understand the biology of the disease so we can better treat the most difficult patients.

We owe much thanks to him and his team and, of course, to all the patients in the trial that took the risk of trying a novel therapy and who gave all those extra tubes of their blood to research.

Here is our interview from ASH 2015.

Brian Koffman, MD  10/17/16