FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma

Regulatory approval: On Oct 2, 2026, the FDA 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. Approval was supported by the randomized, open-label BRUIN CLL-313 trial, in which independent review committee–assessed progression-free survival favored pirtobrutinib versus bendamustine plus a rituximab product. Overall survival data were immature at the primary analysis.

FDA approval (Oct 2, 2026)

The FDA approved pirtobrutinib (Jaypirca; Eli Lilly and Company) for adult patients with previously untreated CLL/SLL with no known 17p deletion. Full prescribing information will be posted on Drugs@FDA.

Evidence base: BRUIN CLL-313 (NCT05023980)

BRUIN CLL-313 was a randomized, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. Patients were randomized 1:1 to:

  • Pirtobrutinib (n=141) until disease progression, or
  • Bendamustine + a rituximab product (n=141) for six cycles.

Efficacy

Primary endpoint: PFS by independent review committee.

  • Median follow-up for PFS: 28 months
  • Median PFS: not estimable (NE) with pirtobrutinib vs 33.5 months with control
  • HR 0.20 (95% CI: 0.11–0.37); p <0.0001

OS was immature at the primary PFS analysis; median OS was not reached in either arm. There were 13 deaths total (pirtobrutinib 3 [2.1%] vs control 10 [7.1%]).

Safety (selected)

Most common (≥20%) non-laboratory adverse reactions: upper respiratory tract infections (27%), rash (22%), COVID-19 (21%). Most common (>10%) grade 3/4 laboratory abnormality: decreased neutrophil count. Serious adverse reactions occurred in 28%.

Prescribing information includes warnings/precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

Dosage

Recommended dose: 200 mg orally once daily until disease progression or unacceptable toxicity.

Pirtobrutinib received orphan drug designation.

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