BRUIN 313 and 314 Trials Open the Door for Noncovalent Bruton Tyrosine Kinase Inhibition as Initial Therapy for Chronic Lymphocytic Leukemia.

In the articles that accompany this editorial, continuous treatment with the non-covalent Bruton Tyrosine Kinase inhibitor (BTKi) pirtobrutinib for chronic lymphocytic leukemia (CLL) is compared in phase 3, randomized trials to either a course of bendamustine plus rituximab chemoimmunotherapy (BRUIN 313, previously untreated patients only) or the covalent BTKi ibrutinib (BRUIN 314, patients with previously untreated and relapsed or refractory CLL). Pirtobrutinib was superior with respect to progression free survival in BRUIN 313 and non-inferior with respect to overall response rate in BRUIN 314, with a more favorable safety profile in both studies, providing the first randomized data supporting the potential use of a non-covalent BTKi as a new frontline treatment option for patients with CLL.