ASH 2023 | Extended follow-up of the ALPINE trial: superior outcomes with zanubrutinib in R/R CLL/SLL

The ALPINE study is a large international, Phase III randomized trial that compared the covalent BTK inhibitor zanubrutinib head-to-head with the first generation covalent BTK inhibitor ibrutinib. We have previously reported that zanubrutinib was superior to ibrutinib not just for response rate, but also for progression-free survival with two year follow-up. And so this year, we were able to update to a median study follow-up of 39 months. We continue to see that zanubrutinib is significantly better than ibrutinib in terms of progression-free survival, with 65% of patients remaining progression-free at a three year landmark, compared to 55% with ibrutinib. The effect is even greater in our highest risk 17p deleted patients, where 59% are in remission with zanubrutinib versus 41% with ibrutinib. We did sensitivity analyses to evaluate how much of this was due to efficacy versus patients coming off drug early, and if we limit the analysis to events of progression or death during active therapy, we still see the same effect, suggesting that this is a real efficacy benefit of zanubrutinib. And the safety is also comparable across many parameters, but the cardiac safety is significantly better, with fewer cardiac adverse and serious adverse events, fewer cardiac hospitalizations, fewer cardiac discontinuations and no cardiac deaths compared to six with ibrutinib. The overall atrial fibrillation rate was 7% with zanubrutinib versus 16% with ibrutinib. So we think the results of the ALPINE study strongly support the use of zanubrutinib in relapsed CLL patients.