Evolving Treatment Landscape of BTK Inhibitors in B-Cell Malignancies - Episode 2
Brad S. Kahl, MD: If I have a patient for whom we’re considering initiating treatment in CLL [chronic lymphocytic leukemia], things that I like to know are their FISH status—that’s fluorescence in situ hybridization. So there are CLL FISH panels that can look for deletion 17p, 11q deletions, trisomy 12, 13q deletions. Those are all part of a standard CLL FISH panel. And then nowadays you should probably also do P53 mutational status. The results of these tests can affect your treatment decisions. And then the other thing to look for, if considering starting a CLL patient on treatment, is to look at the IgVH heavy chain gene mutational status. Some patients are unmutated, which is considered unfavorable. Some patients are classified as mutated, and that’s considered favorable in CLL. The result of that test can also influence treatment decisions.
The CLL FISH panel has been around for many years, and we’ve known that it has prognostic value. What has become more apparent in recent years is that it has some predictive value, in terms of how different treatments might work in a patient. The IgVH mutational testing is a newer technology. Historically, we had surrogates for that test—ZAP-70 and CD38 testing—but these were imperfect surrogates for the IgVH mutational testing. Now there are commercial labs that can run this IgVH mutational testing. So forget about the surrogate testing, just do the actual test because that provides a more reliable result.
The thing that these tests can help guide a clinician on is whether to go with some of the newer therapies that are available for CLL. For example, it’s becoming increasingly clear that patients who have IgVH-unmutated disease, that’s the less favorable version, do significantly less well with immunochemotherapy approaches. But they do relatively well with standard immunochemotherapy regimens like FCR [fludarabine, cyclophosphamide, and rituximab] or BR [bendustamine and rituximab]. But if someone has the unmutated version of the disease, you would be more likely to favor some of the newer targeted approaches such as BTK inhibition. As far as the FISH testing, patients who have the 17p deletion, P53 mutations, or even 11q deletions do less well with immunochemotherapy and seem to do substantially better with BTK inhibition. So the results of those tests might influence the kinds of treatment decisions you make.
Transcript Edited for Clarity