Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia

This phase 1/2 trial consisted of 317 patients with CLL or SLL, 247 of whom has experienced treatment failure with a BTK inhibitor (100 of whom also received prior BCL2 inhibitor). Median number of prior lines of therapy was three. All 317 patients received pirtobrutinib, a highly selective, reversible BTK inhibitor, with an overall response rate of 73.3% (95% CI: 67.3-78.7). Most patients (82.2%) experienced partial response with lymphocytosis (95% CI: 76.8-86.7). The median progression-free survival, a secondary endpoint of the trial, was 19.6 months (95% CI: 16.9-22.1). The most common adverse events observed were infections (71%), bleeding (42.6%), and neutropenia (32.5%). Other adverse events typically thought of with BTK inhibitors such as hypertension, atrial fibrillation or flutter, and major hemorrhage occured relatively infrequently with pirtobrutinib when analyzed at a median duration of treatment of 16.5 months (range, 0.2-39.9 months), with 14.2%, 3.8%, and 2.2% of patients experiencing these events, respectively. Pirtobrutinib was well tolerated, with only 9 of the 317 patients dicontinuing treatment due to a treatment-related adverse event, though certainly the limited other treatment options in patients who are refractory to BTK inhibitors and BCL2 inhibitors (1/3 of this patient population) may be a confounding factor in this.