iwCLL 2025 | The BRUIN CLL-321 trial: a Phase III trial of pirtobrutinib in covalent BTKi-exposed CLL/SLL

The 321 clinical trial is a randomized Phase III clinical trial that is comparing the efficacy of pirtobrutinib in relapsed/refractory patients who have already been exposed to a BTK inhibitor, a covalent BTK inhibitor. So compared to the control arms which consist of the association either of a clinical choice between idelalisib plus rituximab or chemoimmunotherapy with bendamustine plus rituximab. And the trial have shown an advantage of the patients enrolled in the experimental arms, so receiving pirtobrutinib, in terms of progression-free survival, which was the main endpoint of the study, compared to the control arm. 

What is interesting is that there is an advantage, also an even more important advantage in terms of time-to-next treatment. So the progression-free survival of the experimental arm is 14 months, whereas the time-to-next treatment is 24 months. So especially in patients who were not previously exposed to the venetoclax treatment, they obtain a 2.5 years of a median time to next treatment. 

So, pirtobrutinib has shown also to have a very good tolerability and safety profile. The main adverse event, treatment emergent adverse events, were pneumonia, whereas both the bleeding events and atrial fibrillation were very low. In the experimental arm, out of 119 patients, only three experienced atrial fibrillation, and two of them already had a previous history of atrial fibrillation. So based on both the time to next treatment and progression-free survival and the good tolerability profile, pirtobrutinib might be a very good option in patients who have already been double exposed to both BTKi and venetoclax-based treatment, who are now basically an unmet clinical need for their pathology.

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