FDA Gives Traditional Approval to Pirtobrutinib in CLL/SLL

Pirtobrutinib (Jaypirca) has been given traditional approval by the FDA for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who were previously treated with a Bruton tyrosine kinase (BTK) inhibitor, according to a press release from the FDA.¹

Results from the phase 3 BRUIN-CLL-321 trial (NCT04666038) led to the updated approval status. Accelerated approval was previously given to pirtobrutinib in 2023 for patients with CLL/SLL who have been given 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.²

Topline data included a median progression-free survival of 11.2 months (95% CI, 9.5-11.4) in the pirtobrutinib arm and 8.7 months (95% CI, 7.2-10.2) in the investigator's choice arm (HR, 0.58; 95% CI, 0.38-0.89; P = .0105). In the investigator's choice arm, there were 119 patients, and 50 crossed over to the pirtobrutinib arm. At an updated analysis, with a median follow-up of 19.8 months, the HR for overall survival was 1.09 (95% CI, 0.68-1.75).

The recommended dosage is 200 mg orally once daily until disease progression or unacceptable toxicity.

Warning and precautions in the prescribing information include infections, hemorrhage, cytopenias, cardiac arrhythmia, and secondary primary malignancies.

References

1. FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. News release. December 3, 2025. Accessed December 3, 2025. https://tinyurl.com/3tyaw463
2. FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma. News release. January 27, 2023. Accessed December 3, 2025. https://tinyurl.com/46vum4ns