BRUIN CLL-314: Pirtobrutinib vs ibrutinib for CLL/SLL

Results from the randomized phase III BRUIN CLL-314 trial (NCT05254743), comparing pirtobrutinib (n = 331) vs ibrutinib (n = 331) in Bruton tyrosine kinase inhibitor (BTKi)-naïve patients with chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or relapsed/refractory (R/R), were recently published in the Journal of Clinical Oncology by Woyach et al. The primary endpoint was the overall response rate (ORR) by independent review committee (IRC) in the intention-to-treat (ITT) and R/R populations. The key secondary endpoint was progression-free survival (PFS).

Key data: The primary endpoint was met; pirtobrutinib demonstrated noninferior ORR vs ibrutinib in the ITT (n = 662; ORR ratio, 1.11; 95% confidence interval [CI], 1.03–1.19; p < 0.0001) and R/R (n = 437; ORR ratio, 1.12; 95% CI, 1.02–1.24; p < 0.0001) populations. The ORR was higher with pirtobrutinib vs ibrutinib in the ITT (87.0% vs 78.5%; p = 0.0035), R/R (84.0% vs 74.8%; p = 0.0175), and TN (n = 225; 92.9% vs 85.8%; p = 0.0886) populations. Investigator-assessed PFS showed a favorable early trend for pirtobrutinib vs ibrutinib in the ITT (18-month PFS rate, 86.9% vs 82.3%; hazard ratio [HR], 0.57; 95% CI, 0.39–0.83; p = 0.0034), R/R (18-month PFS rate, 81.7% vs 79.2%; HR, 0.73; 95% CI, 0.47–1.13; p = 0.1563), and TN (18-month PFS rate, 95.3% vs 87.6%; HR, 0.24; 95% CI, 0.10–0.59; p = 0.0007) populations. The incidence of treatment-emergent adverse events (TEAEs) of any grade was similar between pirtobrutinib (97.0%) and ibrutinib (97.8%), while rates of atrial fibrillation/flutter (2.4% vs 13.5%) and hypertension (10.6% vs 15.1%) were lower with pirtobrutinib vs ibrutinib.

Key learning: Pirtobrutinib demonstrated noninferiority of ORR vs ibrutinib with favorable early PFS trends and improved tolerability, particularly regarding cardiac adverse events (AEs), demonstrating its potential role in the treatment of CLL/SLL.