FDA Grants Traditional Approval to Pirtobrutinib for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

On December 3, 2025, the FDA granted traditional approval to pirtobrutinib (Jaypirca) for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a covalent BTK inhibitor. This builds on its 2023 accelerated approval for patients with CLL/SLL after at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.¹

Efficacy was assessed in the BRUIN-CLL-321 trial (NCT04666038), a randomized, open-label study of 238 patients previously treated for CLL/SLL, including a prior covalent BTK inhibitor therapy. Patients were randomized (1:1) to receive pirtobrutinib or investigator’s choice of idelalisib plus rituximab (IR) or bendamustine plus rituximab (BR). Pirtobrutinib demonstrated improved progression-free survival, with a median of 11.2 months versus 8.7 months in the IR/BR arm (hazard ratio [HR], 0.58; P=.0105). At 19.8 months of follow-up, overall survival showed no significant difference (HR, 1.09).

Warnings for pirtobrutinib include infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary malignancies, hepatotoxicity, and embryo-fetal toxicity. The recommended dose is 200 mg orally once daily until disease progression or unacceptable toxicity.

Reference

1. US Food and Drug Administration. FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. December 3, 2025. Accessed December 4, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic