iwCLL 2023 | The current role of continuous BTK inhibitors in CLL treatment: benefits and drawbacks

So I’m really excited at this meeting, we have a first line therapy session where I’m going to focus on the role of continuous BTK inhibitors and kind of compare that to the standard option of venetoclax and obinutuzumab, and then combination of BTK inhibitor and venetoclax, which is not approved in the United States but is an emerging option. So I think like given those three choices, it’s really important to consider that when talking about the role of continuous BTK inhibitors, just keeping in context of what the other two options are, which are both not continuous, but fixed-duration therapies with either a year of venetoclax and obinutuzumab or BTK inhibitor and venetoclax.

So the continuous BTK inhibitor therapy was the first one of these three standard options that was approved or in widespread clinical use, and has a few advantages. One of them is definitely that it’s very easy for both physicians and for patients, so it’s just continuous oral therapy and a lot of patients prefer to just take a pill every day and go about their business. It’s very easy to start taking, to continue taking, and so it has that convenience factor. Anything that involves venetoclax or an anti-CD20 monoclonal requires visits for monitoring for the venetoclax or infusions, which the continuous BTK inhibitors don’t. Of course, the efficacy is completely outstanding. There’s been several trials showing that continuous BTK inhibitors have compared very favorably, with improved progression free survival compared to standard chemoimmunotherapy regimens, and actually has an overall survival benefit with ibrutinib and the addition of rituximab to ibrutinib in a first line setting compared to our best chemoimmunotherapy, which is FCR. And continuous BTK inhibitors are shown to be suitable in older or less fit patients, just a very effective therapy across a lot of different populations of patients with CLL. Also, there’s evidence in our highest risk patients, like those with deletion 17p, that progression free survival is similar for patients with deletion 17p CLL and those whose CLL does not have deletion 17p, which really levels the progression free survival in the first-line setting for that high risk group, which you don’t necessarily see with the other options. You definitely don’t with venetoclax and obinutuzumab and we’re still kind of feeling that out with the BTK inhibitor and venetoclax combination with additional follow-up.

The drawback, of course, to continuous BTK inhibitor therapy or any continuous therapy is ongoing toxicity. I think people are by now very familiar with the toxicity profile of BTK inhibitors, especially with bleeding and cardiovascular adverse events such as hypertension and arrhythmias. But there is also things that impact quality of life for patients, such as joint and muscle aches, things like that. And with a continuously dosed therapy, there’s continued exposure to even low grade adverse events, which can really impact how patients are feeling. So that’s really the disadvantage and of course, economic- there’s financial toxicity to continuous therapy.

So I think today continuous BTK inhibitor therapy represents an advantage in terms of efficacy for patients with deletion 17p CLL selecting a first treatment. And also offers an advantage for anyone that is looking for a highly convenient and highly effective therapy. And that has to be balanced against the drawback of continued toxicity, which you don’t get with the two fixed-duration options. So I look forward to discussing that with my colleagues.