ASH 2024 | The Phase III BRUIN CLL-321 study: pirtobrutinib in CLL/SLL with prior covalent BTKi

Thank you very much. It’s my opportunity at ASH this year to present the BRUIN CLL-321 study. This is the first randomized Phase III trial among patients with CLL/SLL who had previously been treated with a covalent BTK inhibitor. So this study randomly assigned patients to either pirtobrutinib or investigator’s choice idelalisib rituximab or bendamustine rituximab. Now one of the challenges, there’s no defined standards in this population of patients. What’s the right therapy to use? While many doctors and patients might select venetoclax, the efficacy of venetoclax in this setting is actually somewhat challenging with a median progression-free survival of 2.5 years and a median overall survival of 3.5 years. So we also know that some patients aren’t necessarily appropriate for venetoclax therapy or might have challenges in receiving it. So this looked at pirtobrutinib versus investigator’s choice. What we found was a median progression-free survival of 14 months versus eight and a half months. And the time to next treatment for pirtobrutinib was about two years for those patients on the pirtobrutinib arm. When we stratified by the receipt of prior venetoclax, it was about two and a half years. So patients did quite well on pirtobrutinib. Now I will say that this is a uniquely challenging group of patients. We had over 50% of patients with TP53 abnormalities. Median number of prior therapies was three. One third of patients had received four or more prior therapies. Half of patients had received prior venetoclax. Complex karyotype was seen in 70% of patients who received pirtobrutinib. So this is a group where you would expect very difficult outcomes. But we were able to show that by continuing on-target BTK inhibition, patients could remain on BTK inhibitors, which are very effective, safe regimens. Now the last point I would make is one of safety. We saw statistically significant improvements in multiple parameters including neutropenia, GI toxicity, fatigue, and so forth for pirtobrutinib. Only 5% of patients discontinued pirtobrutinib for safety-related adverse events. So it’s an effective therapy in this challenging setting with a good safety profile.

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