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Chronic Lymphocytic Leukemia Pathways in Practice at Rocky Mountain Cancer Centers
The Journal of Clinical Pathways (JCP) recently spoke with John Burke, MD, Rocky Mountain Cancer Centers, Denver, Colorado, about the current treatment landscape for chronic lymphocytic leukemia (CLL) and how his center ensures a comprehensive approach to patient care. Below is a portion of that interview, lightly edited for clarity. To view the full interview, visit https://bit.ly/3Pmpg37.
JCP: With the increasing focus on personalized medicine, how do you incorporate genomic and molecular information into the treatment decisions for your patients with CLL? Are there specific biomarkers or genetic mutations that you find particularly informative in tailoring treatment plants?
John Burke, MD: In terms of what genetic mutations and biomarkers I use in my practice, I would say there’s several. First, we do a FISH analysis on all CLL patients for mutations that are known to be common in CLL. We also check the mutational status of the immunoglobulin heavy chain variable region, or IGVH, sometimes referred to as IGHV, which we know to be prognostic in terms of treatment outcomes for patients. Finally, we do a next-generation sequencing panel for most of our CLL patients, where of particular interest is the results of a TP53 mutation, which has prognostic implications and may impact one’s treatment to some extent.
One final way of using molecular information is to look for so-called minimal or measurable residual disease, often abbreviated MRD. And that can be done in a couple of ways, one of which is flow cytometry. I personally often use a next-generation sequencing panel called the clonoSEQ when I’m using a fixed duration, venetoclax-based therapy for patients to track their disease in a more detailed fashion than one can do in conventional CBC monitoring.
Those are examples of what information we test for. Exactly how to use that [information] is a little bit debatable. If you look at in the past, when chemoimmunotherapy was commonly used for CLL, I think maybe those test results had a little bit more critical significance, because chemotherapy and immunotherapy might be used for a patient without, say, a deletion of 17p or a TP53 mutation that would confer a higher risk and therefore a less favorable outcome with chemoimmunotherapy. And so, for example, one could choose chemoimmunotherapy for a patient without one of those high-risk mutations but use one of the targeted drugs for patients with the high-risk mutations. Nowadays, where we are applying the targeted drugs and the immunotherapy as opposed to chemo for the large majority of patients, if not all patients, the relevance becomes perhaps a little bit less . . . and if you look at, say, NCCN guidelines, nowadays they pretty much suggest the same regimens whether a patient has those mutations or not.
For example, BTK inhibitors and venetoclax and obinutuzumab as initial therapy for patients with CLL are both reasonable and recommended frontline treatments, whether a patient has a high-risk mutation or not, whether the patient has an IGHV mutational status as mutated or not mutated. So I think the distinction has been blurred a little bit. And the treatments that we typically use, particularly the frontline setting, have been blurred and spread across both those with high-risk mutations and those without high-risk mutations. So one could argue it’s a little bit less critical nowadays to know that information than it was in the past.
There is an argument to be made to use continuous BTK-inhibitor therapy in those with the deletion 17p or TP53 mutation based on what appears to be better progression-free survival in those patients with such therapy, and so many experts now will advise use of the BTK inhibitors as continuous therapy, and those with those mutations over, say, use of a venetoclax–CD20 antibody combination. So that’s a scenario in which one could really use high-risk mutation to pick between targeted therapies. I would still argue that, one, we don’t know that there’s an overall survival benefit for that strategy. And so it’s still very reasonable to use venetoclax as well in such patients. But that’s a scenario in which people do sometimes choose between targeted therapies based on the genetic testing results.
