Management of Chronic Lymphocytic Leukemia in 2020 - Episode 1

Prognostic Factors in Patients With CLL


William Wierda, MD, PhD: Treatment for patients with chronic lymphocytic leukemia has changed dramatically over the last several years with novel therapies now standard for all patients. In this OncLive® Peer Exchange discussion I’m joined by an international panel of experts in the field of leukemia research. Today we will discuss modern approaches to the treatment of chronic lymphocytic leukemia [CLL], and new data that will change the landscape of therapy in the very near future.

I’m Dr William Wierda, professor and medical director and the section chief for chronic lymphocytic leukemia in the Department of Leukemia at the MD Anderson Cancer Center in Houston Texas.

Today I’m joined by Jackie Barrientos, associate professor in the Division of Hematology and Medical Oncology at Zucker School of Medicine at Hofstra/Northwell in Lake Success, New York;

Shuo Ma, associate professor of medicine in hematology and oncology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois;

Dr Stephen Opat, professor and the director of clinical hematology at Monash Health in Melbourne, Australia;

And Dr Carolyn Owen, associate professor at the University of Calgary in Calgary, Alberta, Canada.

Thank you very much for joining us, and let’s begin.

We’re here at ASH [American Society of Hematology annual meeting] 2019, and there are a lot of new data. There have been a lot of new data over the last year since ASH 2018. I think it’s probably best to start with a discussion about patients with chronic lymphocytic leukemia who are about to start treatment, having a discussion about what are factors that we assess, what are prognostic factors that we would like to know for our patients. And let’s start with Carolyn. If you could give us an overview of what your must-have prognostic factors are, and what are the things that you’re thinking about when evaluating patients for CLL.

Carolyn Owen, MD: Absolutely. I think that today we would also agree that patients should require treatment through symptoms meeting iwCLL [International Workshop on Chronic Lymphocytic Leukemia] treatment requirements. There are still clinical trials looking at asymptomatic patients, but the patient would have to be symptomatic in requiring therapy. And at that point, we want to assess some important prognostic factors, including IGHV mutation status, which is routine in most centers now and in some places not yet, but I think that everybody recognizes the importance of that, as well as TP53 aberrancy, either through mutations or through deletion 17p.

Comorbidities and fitness are very important in terms of different toxicities of treatment and choice. So, although interestingly with the advent of the novel therapies where it’s less important, this criteria, I think based on age and fitness that we used to have such strict requirements for, really if you’ve got the TP53 mutation status and IGHV, I think that gives you a lot more information than even age and comorbidities today.

William Wierda, MD, PhD: Is fitness more or less of an issue these days with our immune targeted therapies?

Carolyn Owen, MD: I think it’s less of an issue. I think there’s more similarity in tolerability for the novel therapies across ages and across fitness levels. Obviously, there are certain comorbidities that are more or less important. More cardiac disease with the BTK [Bruton tyrosine kinase] inhibitors, but in general I think it’s much less important than in the era of chemoimmunotherapy, when we really subclassified patients very differently for age—young versus old—with a very big difference in how we approach therapy.

William Wierda, MD, PhD: Any other features? We have some data now with targeted therapy frontline, BTK inhibitor-based therapies, BCL2 [B-cell lymphoma 2 protein] inhibitor-based therapies. Maybe can you talk a little bit for us about renal function and how that might be important in patients, particularly those who you’re considering for BCL2 inhibitor-based therapies.

Stephen Opat, MBBS: Certainly. So, there are a number of patient factors that we consider important when we’re trying to select a frontline therapy for patients with CLL. We know that renal impairment is important if you’re using new drugs like venetoclax with a risk of tumor lysis. Renal impairment was also an important factor in selecting chemoimmunotherapy, which is still important but for perhaps a small subset of patients, patients with poor renal function having worse outcomes with fludarabine-based therapies.

As well as renal function, as Carolyn mentioned, there are cardiac issues, which are important for BTK inhibitors. There’s also, you’ve got to look at other comorbidities, so older patients, the median age of presentation is over 70 years, and these patients have competing causes of death and second cancers and undernutrition. All these are factors in determining which therapy is most appropriate. So, a curative strategy is probably not appropriate for someone who is 96 years old; whereas you’re looking at a different strategy of someone in their 40s.

Transcript Edited for Clarity