FDA expands Jaypirca to first-line treatment of CLL/SLL

On October 2, 2026, FDA approved Jaypirca (pirtobrutinib) for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who do not have a known chromosome 17p deletion. The approval brings the first FDA-approved non-covalent Bruton tyrosine kinase (BTK) inhibitor into the first-line setting for CLL/SLL and applies to most newly diagnosed patients, as chromosome 17p deletion occurs in only about 5% to 8% of cases at diagnosis.

CLL and SLL are closely related B-cell malignancies, with cancer cells found primarily in the blood in CLL and in the lymph nodes in SLL. Most treated patients receive a BTK inhibitor at some point, and many may need only one or two lines of therapy, making the first choice especially important. Unlike ibrutinib, acalabrutinib, and zanubrutinib, which bind covalently, pirtobrutinib belongs to a newer class of BTK inhibitors that bind non-covalently.

Approval was based on results from the phase 3 BRUIN CLL-313 trial, which compared pirtobrutinib with the chemoimmunotherapy regimen bendamustine plus rituximab in patients with previously untreated CLL/SLL without 17p deletion. At a median follow-up of 28 months, pirtobrutinib reduced the risk of disease progression or death by 80% compared with chemoimmunotherapy. Median progression-free survival had not yet been reached with pirtobrutinib, versus 33.5 months with the control regimen. Responses were more frequent with pirtobrutinib, with an overall response rate of 94% versus 81%. Overall survival data remain immature.

The safety profile was generally consistent with previous studies of pirtobrutinib. The most common adverse reactions were upper respiratory tract infections, rash, and COVID-19. Decreased neutrophil counts were the most common grade 3 or 4 laboratory abnormality. Serious adverse reactions occurred in 28% of patients. Labeling includes warnings for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

"This approval is grounded in data from BRUIN CLL-313, which showed a significant delay in disease progression for pirtobrutinib compared to chemoimmunotherapy, along with safety and tolerability consistent with its established profile," said Jennifer A. Woyach, MD, director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center. "Doctors can now consider pirtobrutinib for appropriate patients when initial therapy is needed, not just later in a patient's treatment journey."

Sources: FDA. (2026 Oct 2). FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma; Eli Lilly and Company. (2026 Oct 2). Lilly's Jaypirca (pirtobrutinib), the first-and-only approved non-covalent BTK inhibitor, receives expanded indication from U.S. FDA for certain patients with previously untreated CLL/SLL