Among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who progress after receiving or discontinue covalent Bruton tyrosine kinase (BTK) inhibitor treatment, pirtobrutinib shows potential to be efficacious, according to research published in The New England Journal of Medicine.

Pirtobrutinib — a selective, reversible inhibitor of both wild-type and C481-mutant BTK — recently received approval from the US Food and Drug Administration for the treatment of patients with mantle cell lymphoma who had progressed after BTK inhibitor treatment. For the phase 1/2 BRUIN trial ( Identifier: NCT03740529), researchers evaluated the safety and efficacy of pirtobrutinib among patients with CLL or SLL who had received a prior covalent BTK inhibitor.

Overall, 317 patients were enrolled, of whom 247 had received prior BTK inhibitor therapy. Among the latter cohort, the median patient age was 69 years, 68% of patients were male sex, 99.6% of patients had CLL, the median prior number of therapy lines was 3, and 76.9% of patients had discontinued therapy after receiving a BTK inhibitor.

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The overall response rate was 73.3% (95% CI, 67.3-78.7). Further analysis showed that the median progression-free survival was 19.6 months (95% CI, 16.9-22.1).

In the overall cohort of 317 patients who received pirtobrutinib (including those who had not received prior BTK inhibitor therapy), the most commonly noted adverse events were infection (71%), bleeding (42.6%), and neutropenia (32.5%). A total of 9 (2.8%) patients discontinued therapy because of a treatment-related event.

“These findings indicate that reestablishing BTK inhibition with pirtobrutinib is a potential therapeutic option regardless of whether previous covalent BTK inhibitor therapy is discontinued owing to disease progression, toxic effects, or other reasons,” the authors wrote in their report.

Disclosures: This research was supported by Loxo Oncology. Please see the original reference for a full list of disclosures.


Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389(1):33-44. doi:10.1056/NEJMoa2300696