BTK Inhibitors vs BCL-2 Inhibitors as Frontline Therapy for Patients With CLL

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Asher Chanan-Khan, MD, Mayo Clinic, Jacksonville, FL participated in a debate with Alexey Danilov, MD, City of Hope Comprehensive Cancer Center, La Canada, CA, regarding the best frontline treatment for chronic lymphocytic leukemia (CLL).

Dr Chanan-Khan argued in favor of BTK inhibitors over BCL-2 inhibitors in this treatment setting. In this video, he presents data to support his argument.

Transcript:

I'm Dr Asher Chanan-Khan from Mayo Clinic in Florida and I'm here attending the Lymphoma, Leukemia & Myeloma Congress 2022. It is an exciting time to be here. I always love to come to this meeting in New York because it's a fun time of the year and the meeting is amazing. Anything and everything that you need to know about hematology or hematologic malignancies is here. The world's experts are here, gathered from all over, and I have learned so much on this meeting. I encourage you to tune in and find some areas of your interest and listen to.

In particular, [at the Congress] I was talking about the role of BTK inhibitors, those inhibitors that are approved in CLL. This was a debate with [Alexey Danilov, MD]—and I enjoyed fighting with him over data. I had a position that I would favor the use of BTK inhibitors as a first-line therapy for patients with CLL. While he took the position that BCL-2 [inhibitors] should be used.

Now all of you know that this is a dilemma that we have right now in CLL therapeutics. Both BTK inhibitors and BCL-2 inhibitors are fortunately very effective drugs, leading us to have responses in our patients in the percentage of 90 plus, and progression-free survival over several years. The question is that of the 2 important classes of drug, which ones should we start with? These opportunities did not exist for our patients in the past. And now that we have it, we want to make sure that we sequence them right and we start on the right foot that makes a difference in terms of survival advantage for these patients.

There were many presentations on these medicines for CLL patients, but Dr Danilov and I argued in favor or against of the first-line therapy or which class of drugs should be. I enjoyed telling him that BTK inhibitors have the longest data available in terms of use.

I also was able to share that when you use a BTK inhibitor, you can use it alone. It has low side effects. You don't have to think about any category of patients, whether they're older, frail, high-risk, or low-risk. There's a fixed dose. You can start at that dose and it works. My position against the BCL-2, despite its effectiveness, is that you have to dose-escalate. You have to monitor the patient's kidney functions, their tumor burden for fear of tumor lysis syndrome, and over 50% of these patients actually have neutropenia.

Dr Danilov's position was that you can use venetoclax for a fixed duration versus when we use BTKis, you give it indefinitely. And that was an important point in some patients and I give that to him. When you are considering therapy, you may want to consider time-limited therapy vs continuous therapy. I think that will depend on the kind of patients you're treating. That’s an important point to consider when you are prescribing.

Now, clinically, apart from this debate, both these drugs are very important for patients. I think we should take into consideration what the patient that is sitting in front of you actually requires. And in that category, you should look at the risk factors. You should look at the age, you look at the quality of life that you want to achieve for them.

Source:

Chanan-Khan, A. BTKi Versus BCL2i - Which is Better? How Best to Use? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.