The U.S. Food and Drug Administration has approved pirtobrutinib for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma who do not have a specific genetic change called del(17p). The agency approved the once-daily pill, sold as Jaypirca, following results from a large clinical trial.
Improved Outcomes in Clinical Trials
The randomized, open-label study, known as BRUIN CLL-313, included 282 patients with previously untreated CLL or SLL who lacked the del(17p) genetic alteration. Patients were randomly assigned to take pirtobrutinib or a standard chemoimmunotherapy combination of bendamustine and rituximab for six cycles.
At an estimated median follow-up of 28 months, the drug significantly delayed disease progression compared with the control group. The hazard ratio was 0.20, meaning the risk of cancer worsening dropped by about 80% with pirtobrutinib. The median progression-free survival was not estimable in the treatment group compared with 33.5 months in the chemoimmunotherapy group.
Investigators reported three deaths in the pirtobrutinib group and 10 deaths in the BR group. While overall survival data were immature at the time of the primary analysis, the median OS was not reached in either group.
Usage and Safety Profile
Dr. Jennifer A. She highlighted that the efficacy and tolerability of modern targeted therapies, combined with patient factors like age or comorbidity, make early treatment choices critically important.
Pirtobrutinib is the only approved noncovalent Bruton tyrosine kinase (BTK) inhibitor for untreated CLL/SLL and received traditional approval for relapsed or refractory disease in 2025. “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.”
Decreased neutrophil count was the most common laboratory abnormality reported. Serious adverse reactions occurred in 28% of patients.
Doctors typically prescribe the drug at a dose of 200 mg orally once daily. The FDA’s approval comes just months after the agency granted traditional approval for the treatment in relapsed or refractory disease. 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.
The most common adverse reactions, which occurred in at least 20% of patients who received pirtobrutinib, were upper respiratory tract infections, rash, and COVID-19. The FDA noted warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity in pirtobrutinib’s prescribing information.