U.S. FDA Approves Pirtobrutinib (Jaypirca) for First-Line CLL/SLL

On October 2, 2026, the U.S. Food and Drug Administration (FDA) approved pirtobrutinib (Jaypirca, Eli Lilly) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) without a 17p deletion.

CLL and SLL are slow-growing blood cancers that affect white blood cells called lymphocytes. CLL is one of the most common types of leukemia in adults. About 22,760 people in the United States are expected to be diagnosed with CLL this year. CLL and SLL are closely related. In CLL, cancer cells are found mainly in the blood. In SLL, they are mainly found in the lymph nodes.

A 17p deletion means part of chromosome 17 is missing. This change is found in about 5% to 8% of people with CLL or SLL when they are first diagnosed. It makes CLL more high-risk. The new pirtobrutinib approval is for people without a known 17p deletion.

Pirtobrutinib was previously approved for adults with relapsed or refractory CLL or SLL who had received a covalent BTK inhibitor. Relapsed means CLL returned after treatment. Refractory means prior treatment did not work to control the cancer. This expanded approval means pirtobrutinib can now be used as a first treatment for some people with CLL or SLL.

"Doctors can now consider pirtobrutinib for appropriate patients when initial therapy is needed, not just later in a patient's treatment journey. 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," said Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, in a press release. 

How does pirtobrutinib treat CLL and SLL?

Pirtobrutinib is a non-covalent BTK inhibitor. It is the first and only FDA-approved drug of its class (non-covalent BTK inhibitor). BTK is an enzyme found in several types of B-cell blood cancers, including CLL. Pirtobrutinib targets the BTK pathway using a different binding method than covalent BTK inhibitors.

Pirtobrutinib is taken by mouth as a tablet. The recommended dose is 200 milligrams once a day, with or without food. Treatment continues until the cancer progresses or side effects outweigh the benefits of treatment. 

The study that led to pirtobrutinib’s approval

The FDA based its approval on the Phase 3 BRUIN CLL-313 clinical trial. It included 282 people with previously untreated CLL or SLL without 17p deletion.

Half received pirtobrutinib. The other half received six cycles of bendamustine plus rituximab, a type of chemoimmunotherapy.

Researchers mainly measured progression-free survival. This measures how long a person is alive without the cancer getting worse.

After a median follow-up of 28 months:

• Median progression-free survival had not yet been reached with pirtobrutinib. The median is the midpoint. This means that more than half of the people treated with pirtobrutinib did not have their cancer grow or change after 28 months.

• Median progression-free survival was 33.5 months with bendamustine plus rituximab.

• The percentage of people taking pirtobrutinib who experienced a response to treatment was 94%, compared with 81% receiving bendamustine plus rituximab.

What are the common side effects of pirtobrutinib?

The most common side effects of pirtobrutinib for people with CLL were:

• Anemia (38%)

• Upper respiratory tract infections (27%)

• Low blood counts, especially related to neutrophils (26%) 

• Rash (22%)

• COVID-19 (21%)

• Bleeding to any extent (18%) 

During the clinical trial, fewer than 4.3% of patients permanently stopped pirtobrutinib due to side effects. 

Next steps for people living with CLL or SLL

If you or a loved one has CLL or SLL, ask your healthcare team about how your current treatment is working for you and if pirtobrutinib or ongoing studies may be right for you.

Questions to ask your care team about pirtobrutinib

Consider asking your care team the following questions about pirtobrutinib:

• Do I have a 17p deletion?

• Is pirtobrutinib an option for my first CLL or SLL treatment?

• How does pirtobrutinib compare with my other treatment options?

• What side effects should I watch for while taking pirtobrutinib?

There are some people who may not be good candidates for this medication because of possible severe side effects (pregnant women, patients with renal impairment, and patients over 65 years of age). Each decision to use this treatment should be individualized. 

Sources:

• FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma

• Lilly's Jaypirca (pirtobrutinib), the first-and-only approved non-covalent BTK inhibitor, receives expanded indication from U.S. FDA for certain patients with previously untreated CLL/SLL  

• Jaypirca Prescribing Information