What You Should Know
- Pirtobrutinib offers a valuable option for people with CLL whose disease has progressed on a covalent BTK inhibitor, providing a way to keep targeting the same pathway even after resistance develops or side effects become difficult.
- Clinical studies show that many patients who stop responding to drugs like ibrutinib, acalabrutinib, or zanubrutinib can still respond to pirtobrutinib, a newer “reversible” BTK inhibitor now FDA‑approved for relapsed or refractory CLL/SLL previously treated with a covalent BTKi.
- As Dr. Kathryn A.F. Kline, a hematologist with the University of Maryland, explains, “the big benefit…is that it works,” noting that pirtobrutinib can help both patients whose CLL is growing again and those who struggle with side effects from earlier BTK inhibitors, while ongoing trials explore whether using it earlier could lead to even better outcomes.
Pirtobrutinib (brand name Jaypirca) is a newer type of BTK inhibitor that is noncovalent (reversible). It is different from commonly used first- or second-generation “covalent” BTK inhibitors such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa). Pirtobrutinib is currently FDA-approved for adults with relapsed or refractory CLL/SLL who have previously received a covalent BTK inhibitor.
Read MoreFor many of those patients, pirtobrutinib can offer another effective option. “Many of those patients then respond to pirtobrutinib, the non-covalent BTKi,” Dr. Kline says.
It can also help patients who struggle with the side effects of earlier BTK inhibitors. “There are also patients who have side effects that make it hard to take the covalent BTKis,” she adds, and “for whatever reason, pirtobrutinib is a more tolerable option for them.”
Clinical studies support this approach. In one study, pirtobrutinib demonstrated activity in patients with CLL who had previously received a covalent BTK inhibitor.
More recently, a randomized phase 3 study led to traditional FDA approval of pirtobrutinib for patients with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor. For someone whose CLL is progressing on a covalent BTK inhibitor, switching to pirtobrutinib can offer an alternative effective way to target the same important BTK pathway. Pirtobrutinib may also be an option when side effects from an earlier BTK inhibitor make continued treatment difficult.
Expert Resources for CLL Patients
- CLL Treatment Decision Making — Exploring All Your Options To Find What’s Right For You
- CLL is Not Considered Curable So Treatment May Resume Years Later
- CLL Treatment: The Side Effects to Expect & Why Reporting All New Symptoms is Crucial
- ‘The Eye of the Tiger’ — Why Mindset and Lifestyle are So Important During Treatment for CLL
- A Decade of Progress: New Targeted Treatments Are Redefining What’s Possible For People With CLL
Where Pirtobrutinib Fits In the Treatment Sequence
Pirtobrutinib is generally continued until the CLL progresses or side effects require stopping treatment. An important question remains: should pirtobrutinib be used earlier, before resistance develops? Researchers are studying whether moving pirtobrutinib earlier in the treatment sequence could provide patients with deeper, longer-lasting, or better-tolerated responses.
Dr. Kline stresses that this question is still being studied: “The question of whether to move it up earlier in the sequencing of drugs is just going to depend on these trial results.”
“We want to give our patients the most effective, most tolerable treatment possible in the right order. So we’re waiting to see if clinical trials show that, in fact, it’s more tolerable or produces deeper or longer responses when we use it earlier. Still don’t have that data”
For now, pirtobrutinib represents an important treatment option for people with CLL who have previously received a covalent BTK inhibitor, particularly when the disease has progressed or treatment side effects have become difficult to manage. The goal is to choose the right treatment at the right time while balancing effectiveness, tolerability, and each patient’s individual circumstances.
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