Are There Advances in Next Generation Sequencing for CLL?

Our recent CLL Global Research Foundation Town Hall featured CLL Global President, Dr. William Wierda, and Dr. Constantine Tam from Monash University in Melbourne. CLL patient advocate Jeff Folloder moderated the event. Watch the full webinar.

Transcript

Jeff Folloder:                          

Anne has got a great question for Dr. Tam. Where are we heading in terms of next generation sequencing and CLL?

Prof. Constantine Tam:          

So, there are two aspects to that. So, the first aspect is looking for new genes that may predict the outcome of CLL. So, mixed generation sequencing have uncovered some key genes that allow us to determine how risky the CLL is. In particular, P53 have been very useful for that. But there are other genes like NOTCH1 and SF3B1, which provide information but doesn’t change therapy.

So, with respect to that, I think we’ve pretty much understood the CLL generics as well as we can. So, we’re now looking at finding infrequent genes, but we’re not finding any new genes that would change treatment.

Now, the other role of mixed generation sequencing, of course, is to monitor response to treatment. So, there are two aspects. So, firstly, mixed generation sequencing allows us to look at the MRD status in a much more sensitive manner than flow cytometry. So, instead of finding one cell in 100,000, we’re finding one cell in a million, or one cell and 10 million with mixed generation sequencing. So, as our treatment gets better, mixed generation sequencing allows us to look even deeper, and to find the very few remaining CLL cells in the body. So, that’s a really exciting new technology.

The other aspect of mixed generation sequencing that is exciting is understanding why patients become resistant. So, by looking at the entire BTK and BCL-2 gene, we can understand why some patients stop responding to the drugs. And then we can hopefully use that information to look at other drugs, even within the same class, but you might find other drugs that are actually active against a mutation, and then prescribe another drug within the same class to overcome that mutation.

                                                So, as you pointed out before, Jeff, this is really personalized medicine. This is about finding out within the individual patient what mutations they carry, and how we can target our treatment to cover those mutations.