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EHA 2026 | BRUIN CLL-322 trial update: fixed-duration pirtobrutinib plus VR in previously treated CLL
Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, presents findings from the BRUIN CLL-322 trial (NCT04965493), which compared fixed-duration pirtobrutinib (P) plus venetoclax-rituximab (VR) to VR alone in patients with previously treated chronic lymphocytic leukemia (CLL). The study met its primary endpoint, with approximately 15% absolute improvement in progression-free survival (PFS) in the PVR arm compared with VR at two years. Dr Davids highlights that the triplet regimen was well tolerated and feasible to deliver, even in older patients and those with comorbidities. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So the current standard of care for previously treated CLL is venetoclax plus rituximab as a two-year fixed duration regimen. This is based on the MURANO trial. And we know from the frontline setting that there’s great efficacy of combining BTK and BCL2 inhibitors. There’s true synergy between that. And so we hypothesize that in this relapsed population, if we added pirtobrutinib to the current standard of care, venetoclax and rituximab, as a time-limited fixed duration regimen, that we would see significant benefit with respect to PFS...
So the current standard of care for previously treated CLL is venetoclax plus rituximab as a two-year fixed duration regimen. This is based on the MURANO trial. And we know from the frontline setting that there’s great efficacy of combining BTK and BCL2 inhibitors. There’s true synergy between that. And so we hypothesize that in this relapsed population, if we added pirtobrutinib to the current standard of care, venetoclax and rituximab, as a time-limited fixed duration regimen, that we would see significant benefit with respect to PFS. So the primary endpoint of the study, which is progression-free survival by an independent review committee, was strongly positive in favor of PVR over VR, with a hazard ratio of 0.54 and about a 15% absolute improvement in PFS with PVR at the two-year time frame compared to VR. Pirtobrutinib was also very well tolerated in this study. The drug tends to not have a lot of additional side effects, and so it became very feasible to deliver the triplet regimen, even in older patients and those with comorbidities who were on the study.
There were also several planned subgroup analyses, which I think are very relevant to the relapsed refractory population, in particular patients who had previously had treatment with covalent BTK inhibitors. And in fact, this is really the first time that we’ve seen a robust data set for venetoclax-based combination therapy in a post-covalent BTK inhibitor population. And the magnitude of the benefit of PFS was actually even greater in the patients who had progressed on prior covalent BTK inhibitor with PVR compared to VR, suggesting that’s a population that may particularly benefit from this new regimen. Similarly, patients with high genetic risk CLL, like those with TP53 aberration, had a significantly improved PFS with PVR. So based on this very favorable efficacy profile along with the favorable safety profile, we hope that our study will actually define a new standard of care for relapsed refractory CLL, which would be PVR, that can be used across a broad population of patients.
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