BTK Inhibitors in CLL: Treatment Selection

Transcript:

Tara Graff, DO, MS: One of the things we’re lacking right now is a head-to-head trial comparing acalabrutinib versus ibrutinib. We know the individual study data: iLLUMINATE, ELEVATE-TN, RESONATE. We know all the information, and we can pull out and tweak—“OK, this is better than this.” But we truly need a head-to-head trial looking at ibrutinib compared with acalabrutinib.

Again, ibrutinib has been used for years. Patients have responded very well. Unfortunately, again, we have the adverse-effect issue. But none of us can say for certain that 1 is better than the other without looking at them directly compared with one another. So I think we need to do that. When you think about competition, you know you’re going to have half the physicians saying, “This 1 is better,” and half the physicians saying, “This 1 is better.” To really prove that, we’re going to need some scientific evidence.

Knowing all the information we do now—the adverse effect profile of ibrutinib, the adverse effect profile of acalabrutinib, the efficacy of acalabrutinib, specifically—I would use acalabrutinib in the first-line setting. I wouldn’t hesitate, and I have not hesitated to use it as first-line monotherapy. Going back to ELEVATE-TN, when you’re looking at the data of acalabrutinib monotherapy—not compared with but individually looking at the data with acalabrutinib plus obinutuzumab—for a patient who is a little older, I don’t want to possibly increase the risk of bone marrow suppression with obinutuzumab. I probably will use acalabrutinib alone, and I have. In fact, I’ve started 4 new patients on acalabrutinib for CLL [chronic lymphocytic leukemia] in the last 3 weeks, and I have not started obinutuzumab with it, because I know the data and I don’t feel it’s necessary right now. However, that doesn’t mean I won’t add it later.

For me, even looking at the NCCN [National Comprehensive Cancer Network] Guidelines, forget my opinion, it’s there—first line. Whether you have a 17p deletion or you are without the 17p deletion, it’s frontline acalabrutinib plus or minus obinutuzumab. And so for me, personally, I would use it as first-line treatment in any situation. High-risk cytogenetics, over age 65—it really doesn’t matter. I think the drug has proven its worth, and I think that people are doing really well.

We get asked, “Well, if there’s a patient who is intolerant of ibrutinib, would you consider switching to acalabrutinib?” The answer is, yes. It has been shown that a substantial amount of patients who have adverse effects warranting discontinuation of ibrutinib—I think close to 70%—when they switch to acalabrutinib the adverse effects go away. Additionally, 13% of patients who still experience adverse effects when they’re switched to acalabrutinib are grade 1. They’re very tolerable and patients can take the acalabrutinib without any issues. So to think that 1 BTK [Bruton tyrosine kinase] inhibitor—you know, 1 and done—that’s not true at all. Patients do fare quite well when switched from a first-generation agent, such as ibrutinib, to acalabrutinib.

Transcript Edited for Clarity