FDA Approves Pirtobrutinib for R/R Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
On December 3, 2025, the US Food and Drug Administration (FDA) granted traditional approval to pirtobrutinib for adult patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a covalent Bruton tyrosine kinase (BTK) inhibitor. This approval was based on results from the BRUIN-CLL-321 study.
In this open-label study, 238 patients were randomized 1:1 to receive either pirobrutinib (n = 119) or investigator’s choice idelalisib or bendamustine plus rituximab (n = 119). Patients were permitted to crossover to the pirtobrutinib arm upon disease progression. The primary end point was progression-free survival (PFS), assessed via an independent review committee. A key secondary end point was overall survival (OS).
At analysis, median PFS was 11.2 months in the pirtobrutinib arm and 8.7 months in the investigator’s choice arm (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.38 to 0.89; P = .0105). Fifty patients crossed over from the investigator’s choice arm to receive pirtobrutinib. At a median follow-up of 19.8 months, the HR for OS was 1.09.
The recommended dose of pirtobrutinib is 200 mg once daily until disease progression or unacceptable toxicity. Prescribing information includes warning and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, and embryo-fetal toxicities.
Pirtobrutinib initially received accelerated approval in 2023 for adult patients with CLL/SLL who had received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
Source:
US Food and Drug Administration. Accessed December 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic
