FDA granted accelerated approval to pirtobrutinib for CLL and SLL

On December 1, 2023, the FDA granted accelerated approval to the noncovalent BTK inhibitor pirtobrutinib for adults with CLL/SLL who had received at least 2 prior lines of therapy, including both a BTK and a BCL-2 inhibitor. Approval was based on efficacy data from the BRUIN trial; 30-month follow-up data was presented at ASH 2023 in San Diego. Overall response rate (ORR) in patients with CLL who had received prior covalent BTK inhibitors was 72%, increasing to 82% if partial response with persistent lymphocytosis (PR-L) was included in the ORR. Median duration of response varied by whether patients had prior exposure to BCL2 inhibitors such as venetoclax. Median duration of response (DOR) was 18.4 months (95% CI, 15.3-20.4) for all patients who had received prior treatment with covalent BTKi (prior-cBTKi), 24.9 months (95% CI, 18.4-32.0) for prior-cBTKi patients who had not previously seen a BCL2 inhibitor such as venetoclax, and 14.8 months (95% CI, 12.0-17.4) for patients with prior exposure to both cBTKi and BCL2 inhibitor. In the CLL/SLL cohort (N=282) of the BRUIN study, the most frequent treatment-emergent adverse events included fatigue (36.9%), diarrhea (28.4%), cough (27.3%), and contusion (26.2%). Grade 3 or greater adverse events (AEs) of interest with BTK inhibitors such as hypertension and atrial fibrillation were low (4.3% and 1.8%, respectively), and only 2.5% of patients discontinued pirtobrutinib due to AEs. However, this low treatment discontinuation rate due to AEs may also reflect that this is a heavily pre-treated population without many other therapeutic options at this time.