Multinational randomized trial of pirtobrutinib versus ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL

A multinational randomized trial compared the noncovalent Bruton tyrosine kinase inhibitor (BTKi) pirtobrutinib versus the convalent BTKi ibrutinib in patient with treatment-naïve or relapsed/refractory (R/R) chronic lympocytic leukemia/ small lymphocytic lymphoma (CLL/SLL). The trial included 662 BTKi-naïve patients, who were randomized 1:1 to pirtobrutinib or ibrutinib. Primary endpoints were overall response rate (ORR) by independent review committee (IRC) among all randomized patients and among patients with R/R disease. The study met both primary endpoints, demonstrating statistically significant noninferiority (NI) of IRC-ORR for pirtobrutinib versus ibrutinib in both the ITT population (87% versus 78.5%; p<0.0001) and the R/R population (84.0% versus 74.8%; p<0.0001). In treatment-naïve patients, IRC-ORR was 92.9% with pirtobrutinib versus 85.8% with ibrutinib. Investigator-assessed progression-free survival favored pirtobrutinin in the ITT population and the treatment-naïve population. Cardiac adverse events rated of atrial fibrillation/flutter and hypertension were lower with pirtobrutinib. The authors conclude that pirtobrutinib demonstrated NI of ORR versus ibrutinib, with a favorable early PFS trend and a favorable safety profile.