ICML 2025 | Real-world effectiveness of first-line covalent BTK inhibitors in patients with CLL

so for my poster that I presented here at ICML and at EHA, we used the Flatiron medical record analysis tool to look at over a thousand patients, it was close to 1200, and it was trying to compare the use of the three different covalent BTK inhibitors in the first-line setting for the treatment of symptomatic CLL. So that’s going to be ibrutinib, acalabrutinib, and zanubrutinib. And we started back in 2020 looking at the distribution of prescriptions, which at that time was dominated by ibrutinib, a little bit of acalabrutinib. And then we saw from 2020 to 2021 to 2022, acalabrutinib took the majority of the share of the BTK usage, but then starting in 2023, you know, zanubrutinib was then available and you started seeing an interesting trend where ibrutinib is getting close to zero, you know, less than 10%. And by the last year that we analyzed, 2024, the split between zanubrutinib and acalabrutinib was almost equal with a little bit higher use of zanubrutinib prescriptions. So that was one interesting finding. But of course, more of what we were interested in was looking at efficacy and tolerability. The drugs zanubrutinib and acalabrutinib have both been compared respectively in the relapse setting in prospective trials, and we know those results. One thing we were interested in seeing is would we find differences in efficacy between zanubrutinib and ibrutinib in the first-line setting like we saw in the ALPINE trial where there was superior progression-free survival, and in fact, we did. For the real-world analysis, we had to use time to next treatment. That’s a surrogate marker for PFS with real-world data. It’s difficult to see the exact progression point when you’re looking at just retrospective medical records. So the real-world time-to-next treatment median was not reached for zanubrutinib or acalabrutinib, but for ibrutinib was around 38 months. So there was a statistically significant difference there between zanubrutinib and ibrutinib, like what was mirroring what was seen in the ALPINE trial. So that was one point we were very interested in seeing. Didn’t necessarily expect to see differences emerge at this point with only a median of a couple of years of follow-up, particularly with the zanubrutinib patients, between acalabrutinib and zanubrutinib, so no statistically significant differences there or in time to discontinuation of treatment, which was also not reached for zanubrutinib but only about 22 months for ibrutinib. I believe it was around 44 months for acalabrutinib, but again, no statistical significant difference there. Very interesting, though, we did observe an overall survival improvement relative to zanubrutinib over ibrutinib. Again, no difference with acalabrutinib at this point. So that really, I think, speaks to the importance of choosing the superior covalent BTK second-generation inhibitors as a first-line treatment over ibrutinib. I think this is going to be an important observation to keep in mind with potential influence on insurance and companies that might be there with the Inflation Reduction Act that might push ibrutinib use as a first-line treatment choice based on cost savings. So I think this could have implications on decisions like that.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.