Dr Lamanna on Considerations for Pirtobrutinib Use in Pretreated CLL

"Our goal is always to think about how we sequence these therapies and how we can get the most mileage out them for patients with CLL. The indications that we would think about [when considering] which patients to choose for pirtobrutinib would be [those with] progressive disease, cytopenias, new lymphadenopathy, and constitutional symptoms that go along with that."

Nicole Lamanna, MD, a hematologic oncologist at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Irving Medical Center, discussedtolerability and disease considerations when determining whether to initiate treatment with pirtobrutinib (Jaypirca) for patients with pretreated chronic lymphocytic leukemia (CLL).

Pirtobrutinib represents a key addition to the therapeutic landscape for chronic lymphocytic leukemia (CLL) as the first non-covalent BTK inhibitor to receive regulatory approval, Lamanna began. In December 2023, the FDA granted an accelerated approval to the agent for the treatment of adult patients with CLL or small lymphocytic lymphoma who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.

Its clinical utility is largely informed by findings from the phase 1/2 BRUIN trial (NCT03740529) study, which evaluated the agent in heavily pretreated populations, particularly those refractory to both covalent BTK inhibitors and BCL2 inhibitors, Lamanna detailed. In current practice, pirtobrutinib is primarily used in this double-refractory setting, where most patients now eligible for the agent, she explained.

Treatment indications in the relapsed setting remain consistent with frontline decision-making criteria, focusing on evidence of disease progression, such as cytopenias or symptomatic lymphadenopathy, rather than shifting therapies in the absence of clinical need, Lamanna noted. This is particularly relevant in the context of CLL’s chronic nature, where therapeutic sequencing is critical to maximize long-term disease control, she added.

A frequent clinical question pertains to switching therapies in patients who are doing well on covalent BTK inhibitors. In such cases, Lamanna emphasized that there is no rationale for transitioning to pirtobrutinib or another agent solely based on drug availability or theoretical benefit. Preserving therapeutic options for future use is a key principle, particularly for younger patients expected to require multiple lines of therapy over time, she stated. However, for patients experiencing intolerance to a BTK inhibitor, a switch to a different agent within the same class—or to pirtobrutinib—may be warranted, she clarified.

Ultimately, the choice to initiate pirtobrutinib should be guided by clear clinical indications, such as disease progression marked by worsening cytopenias, new or enlarging lymphadenopathy, or emergence of constitutional symptoms, Lamanna concluded.