FDA Approves First-Line Pirtobrutinib for CLL/SLL With No Known 17p Deletion

The FDA has approved pirtobrutinib (Jaypirca, Eli Lilly and Company) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion. The approval was issued on October 2, 2026. According to Lilly, the new indication allows the non-covalent Bruton tyrosine kinase (BTK) inhibitor to be used as first-line treatment for appropriate patients.

Pirtobrutinib comes as 100mg and 50mg tablets. The recommended dose is 200mg orally once daily until disease progression or unacceptable toxicity. Its other labeled indications are adults with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor and adults with relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor, under accelerated approval. Pirtobrutinib received orphan drug designation.

The approval was based on BRUIN CLL-313, a randomized, open-label, active-controlled phase 3 trial. It enrolled 282 patients with previously untreated CLL/SLL without 17p deletion, randomized 1:1 to pirtobrutinib (n=141) or bendamustine plus a rituximab product (BR; n=141) for 6 cycles. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee. At a median follow-up of 28 months, median PFS was not estimable with pirtobrutinib and was 33.5 months with BR (hazard ratio, 0.20; 95% CI, 0.11-0.37; P<0.0001). Overall survival data were immature, with 3 deaths (2.1%) in the pirtobrutinib arm and 10 (7.1%) in the BR arm.

Lilly reported an overall response rate of 94% with pirtobrutinib and 81% with BR. The most common non-laboratory adverse reactions with pirtobrutinib were upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). The most common grade 3 or 4 laboratory abnormality was decreased neutrophil count. Serious adverse reactions occurred in 28% of pirtobrutinib-treated patients, and adverse reactions led to permanent discontinuation in 4.3%. The labeling includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

According to Lilly, patients with significant cardiovascular disease, including uncontrolled or symptomatic arrhythmias, were excluded from BRUIN CLL-313. The company said the trial results were published in the Journal of Clinical Oncology. The FDA stated that full prescribing information will be posted on Drugs@FDA.

Sources: US Food and Drug Administration. FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. US Food and Drug Administration; October 2, 2026. Accessed October 5, 2026.

 Eli Lilly and Company. 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. Press release. Eli Lilly and Company; October 2, 2026. Accessed October 5, 2026.