FDA Expands Pirtobrutinib to First-Line Treatment of CLL/SLL Without 17p Deletion

Clinical Summary:

• Regulatory Update: The FDA approved pirtobrutinib for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) without a known 17p deletion.
• Key Outcomes: In the BRUIN CLL-313 trial, pirtobrutinib significantly improved progression-free survival (PFS) compared with bendamustine plus rituximab, reducing the risk of disease progression or death by 80%. Overall survival (OS) data were immature at the primary PFS analysis.
• Clinical Relevance: The approval moves pirtobrutinib into the first-line treatment setting for eligible patients with CLL/SLL, providing a once-daily treatment option that demonstrated superior PFS compared with bendamustine plus rituximab.

Based on results from the BRUIN CLL-313 trial, the US Food and Drug Administration (FDA) has approved pirtobrutinib (Jaypirca; Eli Lilly and Company) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) without a known 17p deletion.

In this open-label, active-controlled trial, 282 patients with previously untreated CLL or SLL without deletion of chromosome 17p were randomized 1:1 to receive either pirtobrutinib (n = 141) or bendamustine plus a rituximab product (n = 141). Pirtobrutinib was administered until disease progression or unacceptable toxicity, while bendamustine plus rituximab was administered for 6 cycles. The primary end point was progression-free survival (PFS), as assessed via independent review.

At an estimated median PFS follow-up of 28 months, median PFS was not estimable in the pirtobrutinib arm and 33.5 months in the bendamustine plus rituximab arm. Pirtobrutinib reduced the risk of disease progression or death by 80% compared with bendamustine plus rituximab (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.11 to 0.37; P < .0001).

Overall survival (OS) data remained immature at the time of the primary PFS analysis. Median OS was not reached in either treatment arm. A total of 13 deaths had occurred, including 3 deaths in the pirtobrutinib arm and 10 deaths in the bendamustine plus rituximab arm.

The most common non-laboratory adverse reactions occurring in at least 20% of patients receiving pirtobrutinib were upper respiratory tract infections, rash, and COVID-19. The most common grade 3/4 laboratory abnormality occurring in more than 10% of patients was decreased neutrophil count. Serious adverse reactions occurred in 28% of patients receiving pirtobrutinib.

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

The approval expands pirtobrutinib into the first-line setting for patients with CLL/SLL without a known 17p deletion, based on the substantial PFS improvement demonstrated over bendamustine plus rituximab in BRUIN CLL-313.

Source: 

US Food and Drug Administration. FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Accessed on: October 2, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pirtobrutinib-previously-untreated-chronic-lymphocytic-leukemia-or-small-lymphocytic