Dr Davids on the Significance of Efficacy Data for Pirtobrutinib Plus VR in R/R CLL

“A question that comes up very frequently now in CLL practice: If you have a patient on a frontline covalent BTK inhibitor and they progress, what should you use in the second line? BRUIN CLL-322 is very reassuring that those patients did particularly well with the pirtobrutinib combination compared with the standard-of-care treatment of venetoclax plus rituximab.”

Matthew S. Davids, MD, MMSc, a physician, the Harold and Virginia Lash Endowed Chair in Lymphoma Research, and chief of the Division of Lymphoma at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed the significance of data for pirtobrutinib (Jayprica) in combination with venetoclax (Venclexta) and rituximab (Rituxan) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) from the phase 3 BRUIN CLL-322 trial (NCT04965493), which were presented at the 2026 EHA Congress.

Data showed that at a median follow-up of 27.3 months, patients who received the pirtobrutinib-based regimen (n = 321) achieved a median progression-free survival that was not estimable (NE; 95% CI, 43.3-NE) vs 39.7 months (95% CI, 35.9-NE) for those who received venetoclax plus rituximab (n = 318; HR, 0.547; 95% CI, 0.400-0.748; P = .0001). Moreover, 24-month PFS rates were 86.9% (95% CI, 82.3%-90.4%) and 71.8% (95% CI, 65.7%-77.0%) for the pirtobrutinib and standard-of-care arms, respectively.

Davids pointed out how the magnitude of benefit seen with the pirtobrutinib combination was significant in comparison with the standard of care regimen. Additionally, he added preplanned subgroup analyses were conducted among subgroups of patients such as those harboring TP53 aberrations and/or 17p deletions, other genetic markers, and prior covalent BTK inhibitor exposure. Among these subgroups, Davids noted that efficacy benefits with the pirtobrutinib-based combination were consistent, especially among patients who had previously been exposed to a covalent BTK inhibitor. Ultimately, Davids concluded by emphasizing that the data from BRUIN CLL-322 make the case for pirtobrutinib plus venetoclax and rituximab as a strong option for patients who have progressed on a covalent BTK inhibitor in the frontline.