Chronic Lymphocytic Leukemia 2021 - Episode 4

Approved BTK Inhibitors for Chronic Lymphocytic Leukemia

Susan M. O’Brien, MD, on the approved BTK inhibitors for treating chronic lymphocytic leukemia.

Susan M. O’Brien, MD: There are 2 BTK inhibitors approved for CLL. One is ibrutinib [Imbruvica], of course, and one is acalabrutinib [Calquence]. Zanubrutinib [Brukinsa] is not yet approved, but likely will be. We have really good choices there. We know that acalabrutinib produces somewhat less atrial fibrillation and hypertension, [which are] the known cardiac risk factors with ibrutinib, but acalabrutinib has to be given twice a day. If you have a patient where compliance may be an issue, then that would not be a preferable drug. The other important difference in terms of usability is that acalabrutinib cannot be used with a PPI [proton pump inhibitor], whereas ibrutinib can. Both are great drugs, and both produce long-term remissions.

There’s no patient in which I would say I would not use a BTK inhibitor. Do I have a patient where I would say it’s an absolute contraindication, no. For example, if I have a patient with atrial fibrillation that’s well controlled, I don’t have to worry about them developing atrial fibrillation and I would still use it in that setting. Some people would perhaps shy away in this setting where a patient has to be on an anticoagulant. We know that ibrutinib or acalabrutinib have some effect on inhibiting platelet function, which is why you frequently have bruising as the most common bleeding side effect with either drug. People might feel like [they do not] want to use a drug that inhibits platelet function, albeit mildly, and be given an anticoagulant. Some people would probably say they would not want to do that. Of course, nowadays, we do have venetoclax [Venclexta] that we could use in that setting. I will say that, before the days of venetoclax where the only good small molecule we had for frontline therapy was ibrutinib, I’ve given it to many people who were on anticoagulation and they’ve done quite well. Again, I don’t have a specific contraindication where I would not use either drug.