FDA Grants Full Approval to Pirtobrutinib for CLL/SLL

The FDA has granted traditional approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton tyrosine kinase (BTK) inhibitor. The approval follows the drug’s accelerated approval in 2023 for patients who had undergone at least 2 prior lines of therapy, including both a BTK inhibitor and a BCL-2 inhibitor, based on clinical trial evidence demonstrating improved progression-free survival (PFS).

Two years earlier, on December 7, 2023, the FDA granted accelerated approval to pirtobrutinib for adults with CLL or SLL who had received at least 2 prior therapies, including a BTK inhibitor and a BCL-2 inhibitor. In the BRUIN (NCT03740529) trial, an open-label study of 108 heavily pretreated patients, pirtobrutinib achieved a 72% (95% CI, 63-80) overall response rate and a median duration of response of 12.2 months (95% CI, 9.3-14.7), with all responses being partial.

The efficacy of pirtobrutinib was evaluated in BRUIN-CLL-321 (NCT04666038), a randomized, open-label, active-controlled trial that enrolled 238 patients with relapsed or refractory CLL/SLL who had previously received a covalent BTK inhibitor. Patients were randomized 1:1 to receive either pirtobrutinib or the investigator’s choice of idelalisib plus a rituximab product (IR) or bendamustine plus a rituximab product (BR), with crossover to pirtobrutinib allowed for those in the IR/BR arm after confirmed disease progression.

Median PFS was 11.2 (95% CI, 9.5-11.4) months for the pirtobrutinib arm vs 8.7 (95% CI, 7.2-10.2) months for the IR/BR arm (HR, 0.58; 95% CI, 0.38-0.89; P = .0105). At a median follow-up of 19.8 months, the overall survival HR was 1.09 (95% CI, 0.68-1.75).

The trial supported pirtobrutinib’s favorable risk-benefit profile, though the prescribing information includes warnings for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary malignancies, hepatotoxicity, and embryo-fetal toxicity.

Pirtobrutinib is recommended at a dose of 200 mg taken orally once daily and continued until disease progression or the development of unacceptable toxicity.

References

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

2. FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. FDA. December 7, 2023. Accessed December 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic