Pirtobrutinib Matches Ibrutinib in ORR, Shows Potential PFS Edge in BTK Inhibitor–Naive CLL/SLL

In the phase 3 BRUIN CLL-314 trial (NCT05254743), pirtobrutinib (Jaypirca) achieved noninferior overall response rates (ORR) compared with ibrutinib (Imbruvica) in patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had not previously received a BTK inhibitor. Notably, early results also suggested a progression-free survival (PFS) advantage with pirtobrutinib, according to data presented by Jennifer Woyach, MD, at the 2025 ASH Annual Meeting and Exposition.

In the ITT population of patients with either R/R or treatment-naive CLL/SLL, the ORR was 87% in patients randomized to pirtobrutinib (n = 331) vs 78.5% in those randomized to ibrutinib (n = 331; P = .0035). The ORR ratio was 1.1080 (95% CI, 1.034–1.187; P value for noninferiority <.0001). The best overall response with pirtobrutinib vs ibrutinib, respectively, was complete remission (CR) or CR with incomplete hematologic recovery (CRi) of 4.8% vs 2.4%, partial remission (PR) or nodular partial remission (nPR) of 82.2% vs 76.1%, partial remission with lymphocytosis (PR-L) of 2.4% vs 3.9%, stable disease (SD) of 5.4% vs 10.9%, and progressive disease (PD) of 1.5% vs 1.2%.

In the treatment-naive population, the ORR was 92.9% in patients randomized to pirtobrutinib (n = 112) vs 85.8% in those randomized to ibrutinib (n = 113; P = .0886). The ORR ratio was 1.0797 (95% CI, 0.989–1.179). The best overall response with pirtobrutinib vs ibrutinib, respectively, was CR/CRi of 7.1% vs 3.5%, PR/nPR of 85.7% vs 82.3%, PR-L of 0.9% vs 2.7%, SD of 2.7% vs 4.4%, and no cases of PD.

In the R/R population, the ORR was 84.0% in patients randomized to pirtobrutinib (n = 219) vs 74.8% in those randomized to ibrutinib (n = 218; P = .0886). The ORR ratio was 1.1233 (95% CI, 1.020–1.237; P value for noninferiority <.0001). The best overall response with pirtobrutinib vs ibrutinib, respectively, was CR/CRi of 3.7% vs 1.8%, PR/nPR of 80.4% vs 72.9%, PR-L of 3.2% vs 4.6%, SD of 6.8% vs 14.2%, and PD of 2.3% vs 1.8%

“Pirtobrutinib demonstrated consistently higher ORR than ibrutinib across all patients, including treatment-naive and R/R populations,” said Woyach, director of the Division of Hematology, The Ohio State University Comprehensive Cancer Center.

PFS data, while immature, showed a trend in favor of pirtobrutinib. In the ITT population, at a median follow-up of 22.0 months with pirtobrutinib and 19.7 months with ibrutinib, the 18-month PFS rates per investigator assessment were 86.9% vs 82.3%, respectively (HR, 0.569; 95% CI 0.388–0.834; nominal P value = .0034). In the R/R population, at a median follow-up of 18.4 months with pirtobrutinib and 15.8 months with ibrutinib, the investigator-assessed 18-month PFS rates were 81.7% vs 79.2%, respectively (HR, 0.729; 95% CI, 0.471–1.128; nominal P value =.1563). And in the treatment-naive population, at a median follow-up of 22.5 months with pirtobrutinib and 22.4 months with ibrutinib, the investigator-assessed 18-month PFS rates were 95.3% vs 87.6%, respectively (HR, 0.239; 95% CI, 0.098–0.586; nominal P value =.0007).

“Early trends in PFS favored pirtobrutinib among all patients and in the R/R and treatment-naive populations,” said Woyach, adding that, “The most pronounced effect [was] in the treatment-naive population, which had the longest follow-up at this data cutoff.”