William Wierda, MD, PhD: Hello, and welcome to this OncLive® Peer Exchange titled “Evolving Therapies in Chronic Lymphocytic Leukemia.” I am Dr William Wierda, from The University of Texas MD Anderson Cancer Center in Houston, Texas.

Joining me today for this discussion are my colleagues Dr John Allan, assistant professor from Weill Cornell Medical Center in New York City; Dr John Burke, associate chair at US Oncology Hematology Research Program at the Rocky Mountain Cancer Centers in Denver, Colorado; and Mazyar Shadman, associate professor from the University of Washington Fred Hutchinson Cancer Research Center in Seattle, Washington.

Today we're going to discuss a number of topics pertaining to first-line therapy for CLL [chronic lymphocytic leukemia] as well as second line and therapies for relapsed/refractory CLL. We’ll discuss the latest research in the field, including updates from the ASCO [American Society of Clinical Oncology] 2020 Virtual Meeting, and the impact of recent clinical trials on making treatment decisions for your patients. Let’s get started on our first topic. We’ll start from the beginning, and that is initial diagnosis and initial work-up for our patients. We’ve seen a revolution in therapies, and we’ll get into that, but let’s start from the beginning and talk a little about the initial work-up and what we’re doing initially for patients in the watch and wait time. We’ll start with you, Dr Shadman. In terms of initial work-up, what's your standard work-up for patients, including the prognostic factor profiling, and how do you use this information?

Mazyar Shadman, MD, MPH: After making a diagnosis for a patient with CLL, usually what happens between a physician and a patient is we talk about some of the prognostic markers that are relevant for CLL and mainly we use them to decide on the best treatment option. Having that information at the time of diagnosis does not necessarily change the plan. In some patients, who may be high risk for the disease, we may decide to have a closer follow-up. Usually, based on the conversations, some of the patients decide to have access to the information at the time of diagnosis, and others decide to have it only when there is a need for treatment.

With the novel agents that we have access to these days, there is a lot of research going on to utilize those drugs earlier in the course, maybe soon after diagnosis. Because of that, having the prognostic information is becoming more relevant even earlier, and maybe even at the time of treatment. For example, from the chemoimmunotherapy era, we know that early intervention, starting treatment doesn't really benefit the patient in terms of helping them live longer, which is the ultimate goal, especially in that space. In the past few years, we have been studying our novel agents in high-risk patients at the time of diagnosis, and unless we have the prognostic markers in hand, we would not be able to offer those trials to the patient. In my practice, I have started having a more serious conversation about the importance of having those markers in patients who are defined as high risk. We may be able to offer them some treatments that are designed for high-risk patients earlier in the course of disease and before they meet the standard criteria for treatment.

William Wierda, MD, PhD: What are you routinely checking?

Mazyar Shadman, MD, MPH: We always start with the FISH [fluorescence in situ hybridization] and karyotype. That’s the most important prognostic and predictive panel to have for a patient with CLL. We have a molecular panel because having information regarding the TP53 mutation specifically, and then a CLL-specific panel, is part of our work-up. If we offer chemoimmunotherapy to the patient, then we will need the information regarding the IGH [immunoglobulin heavy locus] mutational status.

In short, I would say the chromosome analysis, the molecular panel, and IGH mutational status are the standard basic panel that we would need for somebody to define their risk.

William Wierda, MD, PhD: It sounds like those are important when you're thinking about treatment. Do you routinely get them at initial diagnosis when you're in the watch and wait phase?

Mazyar Shadman, MD, MPH: Because we now have studies that are targeting high-risk patients at the time of diagnosis or within the first year from the time of diagnosis, we need to know which patients are high risk, so we have those conversations. If patients are interested in potentially participating in those studies, then we perform the tests at the time of diagnosis. But absolutely, if they don't have that information and when it is time for treatment, we would definitely need to perform those tests.

William Wierda, MD, PhD: That hasn't really changed that much, I think, over the past several years.

Transcript Edited for Clarity