FDA OKs Pirtobrutinib in Frontline CLL/SLL

The FDA has approved pirtobrutinib (Jaypirca) monotherapy as a treatment for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion, according to a press release from the agency.¹

The agency based its decision on data form the phase 3 BRUIN CLL-313 trial (NCT05023980), in which 282 patients were randomly assigned 1:1 to receive pirtobrutinib (n = 141) until progressive disease or bendamustine (Treanda) plus rituximab (Rituxan; n = 141) for 6 cycles. After a median follow-up of 28 months, topline data showed that the median progression-free survival (PFS) was not estimable (NE; 95% CI, NE-NE) with pirtobrutinib vs 33.5 months (95% CI, 32.7-NE) with bendamustine/rituximab. The overall survival (OS) data were not mature at the time of analysis; the median OS was not reached in either arm, and there were 3 deaths (2.1%) in the pirtobrutinib arm and 10 deaths (7.1%) in the benadmustine/rituximab arm.

The most common non-laboratory toxicities with pirtobrutinib included upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). Neutrophil count decreases were the most common grade 3 or 4 laboratory abnormalities. Additionally, 28% of patients had serious adverse effects on pirtobrutinib.

The prescribing information for the agent includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

The FDA approved pirtobrutinib at a dose of 200 mg orally once daily until progressive disease or unacceptable 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. Doctors can now consider pirtobrutinib for appropriate patients when initial therapy is needed, not just later in a patient's treatment journey,” Jennifer A. Woyach, MD, a professor, hematologist-oncologist, and director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, stated in a press release on the approval.² “Given the efficacy and tolerability of modern targeted therapies, coupled with factors like age or comorbidity, many people diagnosed with CLL or SLL today may only receive 1 or 2 lines of therapy, making initial treatment choices critically important.”

References

1. FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. News release. FDA. October 2, 2026. Accessed October 2, 2026. https://tinyurl.com/2vd2wdpu
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. News release. Eli Lilly and Company. October 2, 2026. Accessed October 2, 2026. https://tinyurl.com/shxcp9ma