Pirtobrutinib Expands Treatment Options for CLL
- BTK inhibitors, a type of targeted therapy, have transformed the treatment of chronic lymphocytic leukemia (CLL), helping many patients achieve long-term disease control while reducing the need for traditional chemotherapy.
- Pirtobrutinib (Jaypirca) is a newer, non-covalent BTK inhibitor that can be effective for patients whose CLL has stopped responding to earlier covalent BTK inhibitors such as ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa).
- Researchers are also studying pirtobrutinib in combination with venetoclax and rituximab, with early studies showing deeper, longer-lasting responses in patients with relapsed or refractory CLL.
- Although pirtobrutinib is not yet approved as a first-line treatment, experts say it provides an important new option for patients after BTK inhibitor resistance and reflects the rapid progress improving outcomes for people living with CLL.
North Texas doctors such as Dr. Yair Levy, a hematologist at Baylor University Medical Center in Dallas, tells SurvivorNet the drug is a “wonderful addition,” to the treatment toolbox.
Read MorePirtobrutinib: Giving Patients Another ‘Lifeline’
“Pirtobrutinib is a wonderful addition … we’ve seen that we can get most patients to respond to this non-covalent [BTK] inhibitor despite progression on the covalent,” Dr. Levy tells SurvivorNet. “So, it certainly gives us another lifeline for these patients at their highest unmet need.” Pirtobrutinib (taken as a once-daily pill) has shown encouraging results in patients whose CLL has progressed after treatment with a previous BTK inhibitor, as this drug binds in a different way.Expert Resources for CLL Patients
- CLL Treatment Decision Making — Exploring All Your Options To Find What’s Right For You
- CLL Treatment: What Side Effects Can I Expect From BTK Inhibitors?
- ‘The Eye of the Tiger’ — Why Mindset and Lifestyle are So Important During Treatment for CLL
- ‘Game Changing’ New Treatment Gives Hope to Relapsed CLL Patients
- BTK Inhibitors Play An Important Role In CLL Treatment & Management
Many patients experience another period of disease control, including some whose leukemia has become resistant to earlier BTK inhibitors.
However, Dr. Levy notes that pirtobrutinib is not currently approved as an initial (first-line) treatment for CLL.
“The use of pirtobrutinib now is relegated to people who have already had a covalent [BTK] inhibitor,” he expalins.
Pirtobrutinib in Combination Therapy
Although pirtobrutinib can be taken as a standalone drug after covalent BTK resistance (which can be referred to as a “monotherapy”), there are evolving studies evaluating the drug used in combination with venetoclax (a daily oral pill blocking the BCL-2 protein) and rituximab (an infusion targeting CD20 on cancer cells). Pirtobrutinib can cause serious
side effects, including infections, bleeding, low blood cell counts, abnormal heart rhythms, liver injury, and second cancers.
The drugs are being tested as a “fixed-duration” combination, which means they are given for a specific period of time (as opposed to indefinitely).
Dr. Levy points to the BRUIN CLL-322 phase 3 study, which evaluated these three drugs together in people with relapsed or refractory CLL.
“People did much better in terms of progression-free survival, how long they’re alive without disease getting worse, and in terms of the depth and duration of response with the addition of pirtobrutinib to venetoclax and rituximab,” Dr. Levy says of the findings.
The global, randomized clinical trial enrolled 639 patients in 152 different sites across 22 countries (between October 13, 2021 and October 28, 2024).
Pirtobrutinib: Research & Future Use
Currently, pirtobrutinib cannot be used as a first-line therapy, though Dr. Levy says patients frequently ask about the best way to sequence these drugs/treatment approaches.
“We know from the BRUIN study that pirtobrutinib is a very effective option after failure of a covalent BTK [inhibitor] … But we don’t have very much data at all the other way around,” he explains.
Dr. Levy explains that doctors don’t yet know how well patients respond to older BTK inhibitors after receiving pirtobrutinib first.
“Until we have more clarification on the implications of earlier treatment with pirtobrutinib, I think some of us may be gun shy to do so,” he adds.
Still, the impact of expanding CLL treatment has been incredible. Dr. Levy points out that these drugs have transformed the outlook for CLL patients, allowing them to live long stretches with their disease completely under control.
Questions To Ask Your Doctor
- Am I a candidate for treatment with a BTK inhibitor, and if so, which one is right for me?
- If my CLL stops responding to a covalent BTK inhibitor, could pirtobrutinib (Jaypirca) be an option for me?
- Would I benefit more from taking a single targeted drug or a combination of therapies, such as pirtobrutinib with venetoclax and rituximab?
- Are there any clinical trials studying newer BTK inhibitors or combination treatments that I may be eligible for?
- How will we monitor whether my treatment is working, and what signs or symptoms should I report right away?
Learn more about SurvivorNet's rigorous medical review process.
