Wojciech Jurczak, MD, PhD, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland, shared late-breaking first results from the randomized, open-label, global, phase 3 BRUIN CLL-313 trial demonstrating non-covalent BTK inhibitor pirtobrutinib showed significant improvement in progression-free survival compared with bendamustine-rituximab for patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

These results were presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

At 2 years, 94% of patients receiving pirtobrutinib were progression-free versus 70% with chemoimmunotherapy, with an 80% reduction in the risk of progression or death and favorable tolerability. Dr Jurczak also discussed additional research presented at ASH in pirtobrutinib for patients with R/R CLL.

Dr Jurczak concluded, “we hope that pirtobrutinib as the probably least toxic and most efficient BTK inhibitor will find its place in the early therapy lines.”

Transcript:

Welcome from the ASH meeting in Orlando. I'm Wojciech Jurczak from the National Research Institute Oncology in Krakow, Poland.

It's my great pleasure to summarize pirtobrutinib studies we have here at ASH. It's a good conference for this third generation BTK inhibitor. We presented 2 studies in untreated and relapsing/refractory chronic lymphocytic leukemia. It's perfectly probable that pirtobrutinib will be approved in this clinical setting early in 2026.

In our study, we randomized 280 patients in a third phase protocol between pirtobrutinib and bendamustine-rituximab. At the time we planned this study, chemoimmunotherapy was a justified option, but we could take all treatment-naïve patients except those with 17p deletion, for evident reasons. Now we are able to demonstrate the significant improvement of progression-free survival in pirtobrutinib-treated patients.

The median progression-free survival was not reached, while in the bendamustine-rituximab arm, it was over 34 months. At 2 years, progression-free survival was 94% for pirtobrutinib versus 70% for bendamustine-rituximab, it allowed for an 80% reduction of risk of progression or mortality, and the hazard ratio of 0.2 was better than the hazard ratio of compatible studies with ibrutinib or zanubrutinib. 

Even more important, we could have demonstrated the trend in overall survival, although the data are yet immature, we hope that this will happen. At 2 years, we observed 98% of patients alive in pirtobrutinib arm, versus 94 in a competitor. It should be mentioned that pirtobrutinib was very well-tolerated and all adverse events, specifically if we adjusted it for the length of exposure, were less frequent in pirtobrutinib, perhaps except of a bleeding tendency, which was minor with only 1 patient having CTCA grade-free event. 

Going back to overall survival, this trend we reported was seen despite the crossover, which we offered to 18 out of 34 relapsing patients, which means over 55% of patients were eventually given pirtobrutinib. Our colleagues have a study where they randomized pirtobrutinib versus ibrutinib in both untreated and relapsing refractory patients. Similar to our approach, they could have demonstrated a significant improvement of progression-free survival, which corresponds to our data.

The impact of our study is probably smaller than at the time we planned it. Monotherapy, a time-unlimited approach is reserved for patients with 17p deletions and maybe for the subgroup of elderly individuals, with no intention to treat them beyond the first-line. Nowadays it'll not be the dramatic change in medical practice.

Although, we hope that pirtobrutinib as the probably least toxic and most efficient BTK inhibitor will find its place in the early therapy lines—so far it was approved just in relapsing/refractory setting, and for patients failing previous covalent BTK inhibitors.

Source:

Jurczak W, Kwiatek M, Czyz J, et al. Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients. Dec 6-9, 2025; Orlando, FL. Abstract: LBA-3