by Blood Cancer United
WASHINGTON, Dec. 5, 2025 – The FDA this week approved pirtobrutinib (Jaypirca®) for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults whose cancer has returned or worsened after previous treatment with a so-called ‘covalent’ BTK inhibitor such as ibrutinib, acalabrutinib or zanubrutinib.
Pirtobrutinib and the other three line “-tinib” drugs work by targeting the protein Bruton’s tyrosine kinase (BTK) inside CLL/SLL B cells. Pirtobrutinib is called a non-covalent inhibitor and works by a different mechanism than the already approved covalent inhibitors and can be effective when the cancer has become resistant to therapy with the other drugs.
“BTK inhibitors revolutionized CLL/SLL care, offering patients a targeted oral treatment they can take at home. But like many cancer therapies, they may stop working over time,” says Lore, Ph.D., Blood Cancer United® Chief Scientific Officer. “Now patients and their oncologists have an important new option to extend BTK inhibition so that patients remain in remission longer.”
In a randomized study in patients who had previously been treated with one of the covalent BTK inhibitors, the media progression-free survival time for pirtobrutinib-treated patients was 11.2 months compared with 8.7 months in patients treated with investigator’s choice of therapy. At a median follow up time of 19.8 months, the odds of survival were higher for patients treated with pirtobrutinib.
Pirtobrutinib was first approved for CLL/SLL in 2023 as a third-line treatment. This meant it could be given only after a patient had been treated with at least two previous therapies, including a BTK inhibitor and a BCL-2 inhibitor.
Blood Cancer United is funding science to keep advancing CLL/SLL care
BTK inhibitors and the targeted treatment BCL-2 inhibitor venetoclax transformed CLL/SLL treatment by offering an oral medicine in place of a long-used triple-combo chemotherapy that came with significant side effects. Most people’s first treatment today is a targeted therapy.
While targeted therapies can offer durable responses, usually with manageable side effects, at some point CLL/SLL may become resistant to treatment. Blood Cancer United—formerly The Leukemia & Lymphoma Society—is supporting studies that aim to define how cancer cells become resistant to treatment, and studies to determine the best sequence for the use of BTK inhibitors.
Additional research dollars are dedicated to research looking into ways to combine BTK and BCL-2 inhibitors with other effective therapies to keep people in remission even longer.
“The outlook for people with CLL and SLL has improved substantially in recent years, but our goal is to find more effective and even safer treatments and ultimately, a cure,” says Dr. Gruenbaum.
If you or a loved one need personalized disease, treatment or support information, you can contact one of our Information Specialists: https://bloodcancerunited.org/resources/patients/information-specialists