A large phase 3 clinical trial suggests that pirtobrutinib (sold under the brand name Jaypirca) is being studied as a possible first-line option for people with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In December 2025, the U.S. Food and Drug Administration approved pirtobrutinib for adults with relapsed or refractory CLL/SLL who had previously been treated with a covalent BTK inhibitor such as ibrutinib (Imbruvica).

Thanks! You've successfully submitted your vote.

Sign up to view the results!

Continue with Facebook

Continue with Google

Continue with your email

By joining, you accept our Terms of Use, and acknowledge our collection, sharing, and use of your data in accordance with our Health Data and Privacy policies.

Already a Member? Log in

In the study, people with CLL/SLL were treated with either pirtobrutinib or ibrutinib. People who took pirtobrutinib had higher overall response rates (ORR) — the percentage of people whose cancer shrinks or disappears after treatment — compared to those who took ibrutinib. Those who received pirtobrutinib also had fewer heart-related side effects than those who took ibrutinib.

Pirtobrutinib and Ibrutinib Work Differently

Like ibrutinib, pirtobrutinib is a type of drug known as a Bruton tyrosine kinase (BTK) inhibitor. Both pirtobrutinib and ibrutinib target BTK, a protein that helps CLL/SLL cells survive and grow. Blocking BTK can slow or stop the cancer.

The key difference is how the drugs block BTK:

• Ibrutinib is a covalent BTK inhibitor that binds permanently to one specific spot on the BTK protein. Over time, mutations (changes) in that binding spot can make the drug less effective for some people.
• Pirtobrutinib is a noncovalent or reversible BTK inhibitor that binds to BTK differently and can still work even when mutations change the binding spot. It’s also more selective, meaning it targets BTK more precisely and may cause fewer side effects.

Because of these differences, researchers wanted to find out whether pirtobrutinib could work as well — or better — when used as the first treatment, not just after other drugs stop working.

Key Findings From the Phase 3 Trial

The phase 3 trial included 662 people with CLL/SLL, including individuals who had never been treated before and those whose disease had returned or stopped responding to earlier treatments.

Key results included:

• The ORR was 87 percent among people taking pirtobrutinib and 79 percent among those taking ibrutinib.
• Rates of atrial fibrillation or flutter, a change in heart rhythm, were lower among those who took pirtobrutinib (about 2 percent) compared to those who took ibrutinib (about 13 percent).
• Participants taking pirtobrutinib were less likely to need dose reductions and were more likely to stay on treatment compared with those taking ibrutinib.

Progression-free survival was improved among those who took pirtobrutinib. This means they tended to go longer without their disease getting worse. However, more research is needed to confirm this trend.

Why This Matters for People Living With CLL/SLL

For many people with CLL/SLL, treatment is long term, and having more effective and tolerable options — especially early in care — can make a real difference. This study suggests pirtobrutinib may be a promising first-line option for some people, particularly because of its response rates and safety profile, but results can vary from person to person, and all treatments come with potential side effects.

Pirtobrutinib is already approved for certain people whose CLL or SLL has been treated before, and more follow-up is needed before treatment guidelines change. Still, these findings point to a future with more choices for first-line treatment, giving people and their healthcare teams greater flexibility to tailor care based on individual health needs, treatment goals, and preferences.

Read more about how cardiac arrhythmias and other heart problems may be connected to leukemia.

Join the Conversation

On MyLeukemiaTeam, people share their experiences with CLL and SLL, get advice, and find support from others who understand.

Would you be open to trying a newer treatment option if your doctor recommended one? Let others know in the comments below.