iwCLL 2025 | A comparative analysis of the efficacy of ibrutinib vs acalabrutinib in fixed-duration CLL therapy

I have to say that fixed-duration therapy that is based on the combination of BTKi plus venetoclax comes of age. So in other words, now we have several studies that can support this choice of therapy in a patient with CLL especially in up-front therapy. Recently, we published the results of the AMPLIFY trial. AMPLIFY trial is a trial comparing acalabrutinib plus venetoclax with or without obinutuzumab versus a chemotherapy consisting of FCR or BR. Results showed that the acalabrutinib plus venetoclax was able to outperform, in terms of progression-free survival and overall survival, chemoimmunotherapy. 

We have other studies, obviously, with ibrutinib. We have the GLOW trial, which enrolled patients with older and medically unfit. It is a Phase III trial. And we have also the CAPTIVATE trial, which is a Phase II study, enrolling a patient population which is really similar to that of patients enrolled in the AMPLIFY trial. 

So we, in absence of head-to-head comparison, we performed an indirect comparison between patients in the arm, acalabrutinib plus venetoclax of the AMPLIFY versus patients enrolled in the ibrutinib plus venetoclax of the CAPTIVATE. This analysis was performed using a restricted mean survival time, which is a methodology which has been validated for comparing this type of trials. 

So what we have found is that progression-free survival was longer for patients treated with the ibrutinib plus venetoclax in the context of the CAPTIVATE trial. And the results were similar also in the sensitivity analysis, which excluded from the AMPLIFY trial, all patients who died because of COVID-19. At the end, this is the first time that it was compared to the combination of venetoclax plus a BTKi. Obviously, we are thinking about an indirect analysis. So at the end, probably we need a longer follow-up for this study. But it is important that probably this type of difference is able to capture some biological difference, in other words, some higher synergy between ibrutinib and venetoclax in comparison to acalabrutinib plus venetoclax. I think that probably there is the need of a longer follow-up as I said before, but there is also to consider that acalabrutinib is less toxic than ibrutinib, in turn, especially of cardiotoxicity. So I think that at the end, the choice of therapy should be personalized in each patient after an accurate assessment of cardiovascular condition.

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