Dr. Woyach on Ibrutinib Resistance in CLL

Jennifer Woyach, MD, associate professor, The Ohio State University, discusses ibrutinib (Imbruvica) resistance in patients with chronic lymphocytic leukemia (CLL).

Woyach and her colleagues at The Ohio State University have a large cohort of 308 ibrutinib-treated patients who were treated on 4 clinical trials. She explains that they have been following these patients to look at drug discontinuation and mechanisms of resistance in those patients.

After a median follow-up of 3.4 years, these researchers have observed 27 patients progress with Richter’s transformation and 55 patients progress with CLL. According to Woyach, Richter’s transformation tends to occur in the first 18 months, whereas patients progressing with CLL on ibrutinib tend to do so after 2 years of treatment.

The data show that 46 patients with progressive CLL had samples at relapse available for deep sequencing. At the time of relapse, 87% of these patients had developed mutations in either BTK or PLCG2, which essentially verifies that these are the most dominant mechanisms by which patients relapse, she explains.