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Although clinical response rates in relapsed and refractory chronic lymphocytic leukemia (CLL) are high with the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib, understanding mechanisms of loss of treatment response is important. In the current study, investigators utilized whole-exome sequencing of CLL cells obtained at baseline and at the time of disease progression to identify acquired mutations mediating resistance.
Six patients with acquired resistance were studied following ibrutinib treatment durations of 388 to 868 days. Two patients had achieved complete remission, and four patients had achieved partial remission. Five patients had acquired identical mutations in the BTK gene at the ibrutinib binding site: a substitution of c…