Ferrajoli on the Impact of Comorbidities and Available Therapies in CLL

Alessandra Ferrajoli, MD, hematologist/oncologist, associate professor of medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the comorbidities that can impact the management of patients with chronic lymphocytic leukemia (CLL) and some of the available treatment options in this space, including BCL2 inhibitors and Bruton's tyrosine kinase (BTK) inhibitors.

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0:09 | So, there are 2 main comorbidities that we look at in this specific situation. One is renal failure, and that is very important for the BCL2 inhibitors because those agents need to be given to patients that have a certain creatinine clearance, at least 35 CC per minute. They have to maintain renal function because of the risk of what we call tumor lysis syndrome. That is a release of chemicals in your bloodstream related to the effect of the therapy on leukemia. For BTK inhibitors, instead, the main toxicity we look at is cardiovascular history, in particular, the risk for arrhythmias, prior history of arrhythmias, or ongoing cardiac arrhythmias.

0:58 | Since we live at what I call an age of plenty, those treatments are very good. So, we can just start with the one that we feel is the best fit for that patient. For example, if a patient has a compromised renal function or there is a tumor bulk that is such that I will be worried in regard to tumor lysis syndrome, then I will probably steer that patient toward the program that contains mostly BTK inhibitors. If it is a patient that has had a lot of problems with atrial fibrillation, atrial fibrillation that tends to be recurrent, that is difficult to control, or hypertension that is very difficult to control, a history of hypertensive emergencies, then I will say that patient should not receive certain BTK inhibitors, and is best, probably, to use BCL2 inhibitors.

1:53 | As far as BCL2 inhibitors, we have venetoclax [Venclexta] that is available, and then we have another agent called sonrotoclax [BGB-11417], and that is in clinical trials. For BTK inhibitors, the list is much longer. We have ibrutinib [Imbruvica], that was the first one that was developed, and it is considered a first-generation BTK inhibitor. Then, we have second-generation BTK inhibitors, and we have 2 that are approved: Acalabrutinib [Calquence] and zanubrutinib [Brukinsa]. Now, we also have a new type of BTK inhibitor. They are the non covalent BTK inhibitor, and we have pirtobrutinib [Jaypirca].