Thanks for asking about the BRUIN CLL-313 study. It was a randomised multicentre protocol where we took 280 treatment naïve chronic lymphocytic leukaemia patients with indications for [??] according to IWCLL 2018 criteria, excluding those with 17p deletion. We randomised them against chemoimmunotherapy, which at the time we planned the study was allowed as one of the options – it was bendamustine/rituximab – versus pirtobrutinib once daily. Again, at the time we planned the study monotherapy with BTK inhibitors was fully justified to the majority of patients.
What was the study design?
Our primary target was the progression free survival assessed by independent revision committee. The key secondary target was overall survival followed by safety.
I’m glad to say that the study was positive, it has a statistically significant and, perhaps more important, clinically meaningful progression free survival difference. At two years we had 94 patients progression free in the pirtobrutinib arm versus 70 in bendamustine/rituximab. Even more important, the hazard ratio was 0.2, which was one of the highest achieved with a monotherapy with BTK inhibitor against bendamustine/rituximab, and that meant an over 80% reduction of progression or death.
What is the clinical significance of these results?
It’s difficult to say at the moment because in 2025 we tend to treat the majority of our treatment naïve patients with a time-limited regimen, it’s BCL2 inhibitor with anti-CD20 or BTK inhibitor with BCL2 inhibitor. However, we still have perhaps up to 10-15% of patients where we would like to give them a BTK inhibitor given until progression or adverse events. We are talking not just about the patients with 17p deletion, at least some of them might be treated with time-fixed regimens as well, but we are talking about the elderly elderly or the unfit elderly, crippled patients, comorbid, where it’s very likely that the first line of therapy is going to be the only line of therapy in their life. Specifically, we are talking about the population treated by the community practice, far from the university centres, where the charm of a tablet a day without the necessity to see the hospital, to come for the lengthy infusions, to have the risk of infection, is important.
So I wouldn’t say it will be a thunderstorm but it will be a kind of evolution. Pirtobrutinib was originally approved for double-exposed patients after BCL2 and BTK inhibitors. In December 2025 the FDA broadened its rules, now it’s after failing BTK inhibitor. I hope that with the two studies which were presented at ASH, ours and BRUIN 314 where pirtobrutinib was randomised against ibrutinib and 250 patients were treatment naïve in that protocol, and both studies were positive. So I hope that the FDA might approve pirtobrutinib as a monotherapy in treatment-naïve patients in Q1 or Q2 2026.
