The U.S. Food and Drug Administration (FDA) has approved pirtobrutinib (brand name Jaypirca) as a first-line treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not have the del(17p) genetic change. This approval marks a significant advancement in targeted therapy for these conditions, offering a once-daily pill as a new treatment option.
This approval is based on results from the BRUIN CLL-313 clinical trial. The study showed that patients taking pirtobrutinib had a significantly longer time without their cancer worsening compared to those receiving chemotherapy and immunotherapy.
Clinical Trial Results Show Promise
In the phase 3 trial, 282 patients were randomly assigned 1:1 to receive either pirtobrutinib or a combination of bendamustine and rituximab (BR) for six cycles. The study found that pirtobrutinib reduced the risk of disease progression by approximately 80% compared to BR.
At a median follow-up of 28 months, the median progression-free survival (PFS) was not estimable for the pirtobrutinib group, while the BR group had a median PFS of 33.5 months. The study also reported fewer deaths in the pirtobrutinib group (3) compared to the BR group (10).
A New Option for First-Line Treatment
Dr. Jennifer A. Woyach, an investigator from the Ohio State University Full Cancer Center, stated that pirtobrutinib offers a valuable new option for patients needing initial treatment. She emphasized the importance of initial treatment choices, as many patients may only receive one or two lines of therapy due to the effectiveness of modern targeted treatments. “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 one or two lines of therapy, making initial treatment choices critically important,” Dr. Woyach noted.
Pirtobrutinib is the only approved noncovalent Bruton tyrosine kinase (BTK) inhibitor for untreated CLL/SLL. It was previously approved for relapsed or refractory disease in 2025. This unique mechanism of action distinguishes it from other BTK inhibitors, offering a new therapeutic approach for patients.
Side Effects and Dosage
The most common side effects of pirtobrutinib include upper respiratory tract infections, rash, and COVID-19. These adverse reactions occurred in at least 20% of patients, highlighting the need for careful monitoring during treatment. The FDA has issued warnings about potential risks such as infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity. Decreased neutrophil count was the most common grade 3 or 4 laboratory abnormality, reported in at least 10% of patients.
The recommended dosage is 200 mg taken orally once daily until disease progression or unacceptable side effects occur. This dosing regimen offers convenience and flexibility for patients, particularly those treated in community settings.
Experts have noted that pirtobrutinib is particularly well-suited for elderly patients or those treated in community hospitals, where a relatively nontoxic option is preferred. “It’s a good option for elderly patients who are treated in community hospitals, where you want something relatively nontoxic, something that will not provoke any increase in infection rates [or] unnecessary hospital visits,” said Wojciech Jurczak, MD, PhD, from the Maria Skłodowska-Curie National Research Institute of Oncology in Kraków, Poland.