Non-Covalent BTK Drug Wins Broad Approval in Most Common Leukemia

The FDA on Friday expanded the approval of pirtobrutinib (Jaypirca) in chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) to include the first-line treatment of adults whose cancers have no known 17p deletion.

Approval of the non-covalent Bruton’s tyrosine kinase (BTK) inhibitor was based on results from the randomized BRUIN-CLL-313 trial, which showed that pirtobrutinib reduced the risk of disease progression or death by 80% versus chemoimmunotherapy.

Median progression-free survival was not estimable in the pirtobrutinib arm as compared with 33.5 months in the bendamustine (Bendeka, Treanda) plus rituximab arm (HR 0.20, 95% CI 0.11-0.37, P<0.0001). The overall response rate reached 94% with pirtobrutinib versus 81% with bendamustine plus rituximab.

“Doctors can now consider pirtobrutinib for appropriate patients when initial therapy is needed, not just later in a patient’s treatment journey,” investigator Jennifer Woyach, MD, of the Ohio State University Comprehensive Cancer Center, said in a press release from drugmaker Eli Lilly. “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.”

Pirtobrutinib was first approved in 2023 under the accelerated approval pathway for pretreated CLL/SLL and has also shown activity in CLL patients with Richter transformation, a difficult-to-treat population. The non-covalent BTK inhibitor, the only such drug approved in the U.S., is also approved for previously treated mantle cell lymphoma.

The open-label BRUIN-CLL-313 trial also demonstrated that pirtobrutinib’s safety and tolerability was “consistent with its established profile,” added Woyach.

In randomized trials, the most common non-laboratory adverse events (AEs) occurring in patients receiving pirtobrutinib included upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). The most common grade 3/4 laboratory abnormality was decreased neutrophil counts (26%), and serious AEs occurred in 28% of patients.

The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.