Multinational phase 1-2 study of pirtobrutinib after a covalent BTK inhibitor for relapsed or refractory chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have poor outcomes after the failure of covalent BTK inhibitor treatment, and new therapeutic options are needed. Pirtobrutinib is a highly selective, noncovalent BTK inhibitor. The multinational phase 1-2 BRUIN trial evaluated pirtobrutinib for relapsed or refractory CLL or SLL. Among patients who previously received a covalent BTK inhibitor, the percentage of patients with with an overall response to pirtobrutinib was 73.3% (95% CI 67.3-78.7). The median progression-free survival among these patients was 19.6 months (95% CI 16.9-22.1). Among all patients with CLL or CLL who received pirtobrutinib the most common adverse events were infections (71.0% of patients), bleeding (42.6%) and neutropenia (32.5%). Only 2.8% of patients discontinued pirtobrutinib due to a treatment-related adverse event.