Dr Jennifer Brown on the Role of Genomic Sequencing in CLL

Jennifer R. Brown, MD, PhD, director, Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute, and associate professor of medicine at Harvard Medical School, discusses how genomic sequencing plays a role in determining prognosis and treatment for patients with chronic lymphocytic leukemia (CLL).

TranscriptDoes genomic sequencing play a role in determining prognosis and treatment for patients with chronic lymphocytic leukemia?

Certainly, certain genomic prognostic markers are quite important in CLL [chronic lymphocytic leukemia]. Historically, we’ve used chromosome abnormalities as determined by FISH [Fluorescence In Situ Hybridization], with the highest risk abnormality being the deletion of 17p. Now, that’s often accompanied by mutation of the TP53 gene, which we now recognize being similarly adverse to 17p deletion. One thing that was remarkable about venetoclax and rituximab is that there was no difference in progression-free survival (PFS) at 2 or 3 years based on 17p deletion.

That’s actually even better than the BTK [Bruton's Tyrosine Kinase] inhibitors where we actually do see that PFS is a bit shorter in the patients with that very high-risk marker. There are other gene mutations in CLL, as well. NOTCH1 is one that we worry about associated with Richter’s transformation, SF3B1, and ATM. And then a long list of less frequent mutations. We don’t really know yet what the impact of those are in the context of novel agent therapy, and that’s something that we’re all very interested still in studying.