The FDA has expanded approval of pirtobrutinib (Jaypirca) to include first-line treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) whose cancers have no known 17p deletion. The decision moves the non-covalent Bruton's tyrosine kinase inhibitor earlier in the treatment journey, rather than reserving it for later lines of therapy.
The expanded indication is supported by the randomized BRUIN-CLL-313 trial, in which pirtobrutinib cut the risk of disease progression or death by 80% versus chemoimmunotherapy. Median progression-free survival was not reached in the pirtobrutinib arm, compared with 33.5 months for bendamustine plus rituximab, and the overall response rate was 94% versus 81%.
Pirtobrutinib was first approved in 2023 under accelerated approval for pretreated CLL/SLL and is also approved for previously treated mantle cell lymphoma. Investigator Jennifer Woyach of Ohio State University noted that because many patients today may receive only one or two lines of therapy, initial treatment choices are critically important. The most common non-laboratory adverse events included upper respiratory tract infections, rash, and COVID-19, with warnings for infections, hemorrhage, cytopenias, cardiac arrhythmias, and other risks.