ASH 2025 | Fixed-duration and MRD-adapted therapy in CLL: insights from ASH 2025

I would say that the most impactful abstract at this whole meeting was abstract number one, which reported on the results of the CLL17 trial, comparing continuous ibrutinib therapy as a monotherapy to time-limited venetoclax-based therapy, either in combination with ibrutinib or with obinutuzumab. And the study confirmed its primary endpoint, which was non-inferiority of the time-limited therapies compared to continuous ibrutinib monotherapy. All the patients are generally doing quite well in the study, 80% PFS at around three years, very high response rates, et cetera. But one of the challenges of the study is that it’s only exploring the fixed-duration regimens. So all patients get the same length of therapy regardless of their genetic markers or their attainment of MRD. So there’s a number of other studies looking at MRD-guided approaches for frontline CLL treatment. One of the important updates that we saw at this year’s ASH meeting was the UK FLAIR study comparing or combining Ibrutinib with Venetoclax, but doing it as an MRD-guided therapy that was also time-limited. And really, their progression-free survival curves look quite impressive across a range of different prognostic marker subgroups. And they’ve done this through individualizing therapy through MRD guidance. And so it does raise the question of whether we’re sort of leaving some efficacy on the table by only giving about one year of combination therapy, especially for patients with high genetic risk CLL like unmutated IGHV or even TP53 aberration. And many of the patients on the FLAIR study needed three or four years of ibrutinib plus venetoclax to attain undetectable MRD. And we’re seeing now that that translates into an excellent progression-free survival. So at this meeting, we don’t have any head-to-head data comparing these two strategies of fixed duration versus MRD-guided therapy. But fortunately, there are now trials getting underway. For example, the CLL18 study is comparing pirtobrutinib with venetoclax either as MRD-guided or fixed duration to a control arm of fixed duration venetoclax plus obinutuzumab. So we’ll have to wait for a future ASH to get those results.

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