FDA Approves Pirtobrutinib for Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

The U.S. Food and Drug Administration approved pirtobrutinib (Jaypirca) on October 2, 2026, for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma without deletion of chromosome 17p. The approval was based on results from the phase 3 BRUIN CLL-313 trial, which showed a progression-free survival benefit compared with bendamustine plus rituximab, officials said.

Pirtobrutinib, marketed as Jaypirca by Eli Lilly and Company, is approved for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not have a deletion of chromosome 17p, according to the FDA’s announcement on October 2, 2026. This approval marks the first time pirtobrutinib has been authorized for use in the frontline treatment setting for these patients, expanding its indication beyond relapsed or previously treated B-cell malignancies, Eli Lilly officials said.

The trial compared pirtobrutinib monotherapy with the chemoimmunotherapy regimen bendamustine plus rituximab.

The FDA’s decision was based on data from the phase 3 BRUIN CLL-313 trial (ClinicalTrials.gov identifier NCT05023980), a randomized study that enrolled 282 adults with previously untreated CLL or SLL lacking the high-risk del(17p) genetic abnormality. Results demonstrated a statistically significant improvement in progression-free survival for patients receiving pirtobrutinib, according to the FDA’s approval documents and trial reports.

Patients in the study received pirtobrutinib at a dose of 200 mg orally once daily until disease progression or unacceptable toxicity, sources confirmed. Jaypirca is available in 50-mg and 100-mg tablet formulations, facilitating oral administration rather than intravenous infusion. The FDA’s approval specifically excludes patients with known deletion of chromosome 17p, a genetic marker associated with higher-risk disease, reflecting the trial’s enrollment criteria and the population for which the drug’s efficacy and safety were established.

Eli Lilly described pirtobrutinib as a noncovalent Bruton tyrosine kinase (BTK) inhibitor, distinguishing it from covalent BTK inhibitors currently used in CLL and SLL treatment. This reversible binding mechanism is noted as a novel approach in targeting BTK, the enzyme involved in B-cell receptor signaling that contributes to malignant B-cell proliferation. The FDA’s action represents the first approval of a noncovalent BTK inhibitor for initial treatment of CLL and SLL, company representatives said.

The BRUIN CLL-313 trial enrolled adults who were initiating systemic therapy for CLL or SLL and had no known del(17p), a subgroup that excludes patients with this high-risk chromosomal deletion. The study’s primary endpoint was progression-free survival, and the trial met this endpoint with a statistically significant benefit for pirtobrutinib compared to bendamustine plus rituximab, according to published trial data and FDA briefing materials. The safety profile observed in the trial supported continued treatment until progression or toxicity, officials noted.

Chronic lymphocytic leukemia is a malignancy of mature B lymphocytes circulating in the blood, while small lymphocytic lymphoma represents the same disease process primarily involving lymph nodes or other tissues. The deletion of chromosome 17p is a well-recognized adverse prognostic marker in both CLL and SLL, often guiding treatment decisions. The FDA’s approval restricts the new indication to patients without this deletion, consistent with the clinical trial population and evidence base.

The FDA and Eli Lilly simultaneously announced the expanded indication on October 2, 2026. This approval provides an additional oral treatment option for adults with untreated CLL or SLL lacking del(17p), broadening the therapeutic landscape beyond existing chemoimmunotherapy and covalent BTK inhibitor regimens. The FDA’s prescribing information specifies that pirtobrutinib should be administered as monotherapy at 200 mg daily and continued until disease progression or unacceptable adverse effects occur.

Pirtobrutinib’s prior FDA approvals covered its use in certain relapsed or refractory B-cell malignancies, but this new indication marks its entry into the frontline treatment setting. The decision is based on robust phase 3 evidence from the BRUIN CLL-313 trial, which enrolled 282 patients and demonstrated a clear progression-free survival advantage over bendamustine plus rituximab, a standard chemoimmunotherapy regimen. The trial’s results and FDA approval documents emphasize the importance of genetic testing for del(17p) to determine patient eligibility for pirtobrutinib in this setting.

The approval adds to the evolving treatment options for CLL and SLL, diseases characterized by abnormal B-cell proliferation and often requiring systemic therapy when symptomatic or progressive. The restriction to patients without del(17p) aligns with current clinical practice of stratifying treatment based on genetic risk factors. Further research and postmarketing data will continue to inform the role of pirtobrutinib and other BTK inhibitors in managing these hematologic malignancies.