Comparing BTK Inhibitors for Frontline Chronic Lymphocytic Leukemia Treatment

John Allan, MD, Weill Cornell Medicine, New York, compares the use of different Bruton’s tyrosine kinase (BTK) inhibitors for the treatment of chronic lymphocytic leukemia (CLL) in a frontline setting and discusses whether there is an optimal drug regimen to use among patients with CLL.

Transcript:

Dr Allan: I'm John Allan, coming to you from New York City, where I practice at Weill Cornell, where I am a CLL and lymphoma specialist.

Lymphoma, Leukemia & Myeloma Network: In the CLL treatment space, is there a preferred and/or optimal BTK inhibitor to choose for frontline therapy?

Dr Allan: It's a good question regarding [if] there [is] an optimal best in class, you could say, BTK inhibitor? In the frontline settings, it's difficult to state that right now as head-to-head studies are lacking in that space. Those patients are very different than those who are represented in the relapsed/refractory spaces where we do see some differences between toxicity and efficacy amongst our BTK inhibitors.

Right now, we have 1 drug, zanubrutinib, that has shown to have superior progression-free survival over ibrutinib in relapsed/refractory CLL. Another selective BTK inhibitor like acalabrutinib has shown non-inferior disease, but these non-inferior outcomes [are] compared to ibrutinib, but also with an improved toxicity profile. These are also very different studies in very different patient populations. So, extrapolating acalabrutinib against zanubrutinib is rather difficult. What can be said is that there has been a shift towards the more selective BTK inhibitors based on toxicity profile.

My own opinion is that I think most of these drugs are equally effective, but there are some advantages of the more selective drugs such as acalabrutinib and zanubrutinib in terms of that cardiovascular, adverse event profile.

Other advantages, or pros and cons, of different [types] of these agents is dosing schedules and things like that. That doesn't typically impact compliance significantly, but there are some patients who do prefer once daily dosing versus twice, et cetera. So, patient preferences do come into play, but ultimately, it's wherever you have the most comfort. I think all 3 of these drugs, ibrutinib, acala[brutinib], [and] zanu[brutinib] are excellent agents and really it comes down to your comfort, patient preferences and typically there's been a move towards more selective drugs.