FDA approves pirtobrutinib (Jaypirca) for previously untreated CLL/SLL without 17p deletion

On 2 October 2026, the U.S. Food and Drug Administration approved pirtobrutinib (Jaypirca, Eli Lilly) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion. The recommended dose is 200 mg orally once daily until progression or unacceptable toxicity. Pirtobrutinib received orphan-drug designation.

Trial evidence (BRUIN CLL-313)

Efficacy came from BRUIN CLL-313 (NCT05023980), a randomised, open-label, active-controlled trial of 282 previously untreated CLL/SLL patients without 17p deletion, assigned 1:1 to pirtobrutinib (n=141) or bendamustine plus a rituximab product for six cycles (n=141). With an estimated median progression-free-survival (PFS) follow-up of 28 months, median PFS was not estimable in the pirtobrutinib arm versus 33.5 months with chemoimmunotherapy (hazard ratio 0.20; 95% CI 0.11–0.37; p < 0.0001). At the primary PFS analysis, overall survival data were immature (13 deaths total: 3 on pirtobrutinib, 10 on control).

Safety caveats

Common (≥20%) non-laboratory adverse reactions on pirtobrutinib included upper respiratory infections (27%), rash (22%) and COVID-19 (21%); serious adverse reactions occurred in 28%. The label warns about infections, haemorrhage, cytopenias, cardiac arrhythmias, secondary malignancies, hepatotoxicity and embryo-fetal toxicity. This summarises an FDA approval based on one open-label randomised trial with immature OS — not personal medical advice. Patients should discuss options with an oncologist.