Jaypirca improves survival in treatment-naïve CLL/SLL patients | ASH 2025

Jaypirca (pirtobrutinib) improved progression-free survival in treatment-naïve patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) when compared with bendamustine plus rituximab, according to a new study presented at the 67th American Society of Hematology (ASH) Annual Meeting being held in Orlando.

“Pirtobrutinib is a good option for the elderly patients who are treated in community hospitals where you want something relatively nontoxic that will not provoke any increase in infection rate or any unnecessary hospital visits,” Wojciech Jurczak, M.D., Ph.D., head of the department of oncology at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, said during a press briefing.

Chronic lymphocytic leukemia and small lymphocytic lymphoma are slow-growing forms of non-Hodgkin lymphoma that develop when lymphocytes grow out of control and abnormal B cells build up in bone marrow (CLL) or lymph nodes (SLL). The American Cancer Society estimates that in 2025, about 80,350 people will be diagnosed with non-Hodgkin lymphoma, and about 19,390 people will die from this cancer.

Developed by Eli Lilly, Jaypirca was recently granted full approval for adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have previously been treated with a covalent BTK inhibitor. Previously, it was available under an accelerated approval. Jaypirca is also approved to treat adults with relapsed or refractory mantle cell lymphoma.

Jaypirca is highly selective and binds to the molecule that is different from previous BTK inhibitors. It's a non-covalent BTK inhibitor and is able to create a temporary bond with the molecule. It also has fewer side effects than covalent BTK inhibitors, such as Imbruvica (ibrutinib), which forms a permanent bond with Bruton tyrosine kinase.

Relate: Jaypirca shows promise as a frontline treatment for CLL/SLL patients | ASH 2025

Jurczak presented results from the BRUIN CLL-313 trial, a phase 3, open-label study. The trial enrolled 282 patients who were randomly assigned to either Jaypirca or the chemotherapy drug bendamustine plus the monoclonal antibody rituximab, a regimen used in the treatment of patients with chronic lymphocytic leukemia.

Patients in the active comparator arm were able to cross over to receive Jaypirca. In fact, 52.9% of patients who relapsed on bendamustine plus rituximab crossed over to receive Jaypirca, Jurczak said.

The primary endpoint in the trial was progression-free survival as assessed by blinded independent review committee. Secondary endpoints include overall response rate, duration of response, overall survival, time to next treatment, safety and tolerability, and patient-reported outcomes.

In this trial, Jaypirca improved progression-free survival compared with the bendamustine plus rituximab. Overall survival data were not mature, but showed a trend toward favoring Jaypirca. “Pirtobrutinib reduces the risk of disease progression or death by 80%,” Jurczak said.

Jaypirca was well tolerated with low rates of discontinuation and atrial fibrillation or flutter. “Atrial fibrillation, which was common in the first-generation BTK inhibitors, is literally nonexistent with pirtobrutinib,” Jurczak said. “The infections are much less common than with bendamustine and rituximab.” The only safety issue that could have been more frequent with the pirtobrutinib is a minor bleeding tendency.”

Lilly has begun submitting results from BRUIN CLL-313 and BRUIN CLL-314 studies to regulatory authorities. BRUIN CLL-314 is a head-to-head study that compared Jaypirca with Imbruvica (ibrutinib).

The studies were funded by Lilly.