Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor

作者：Jennifer A. Woyach, Lugui Qiu, Sebastian Grosicki, Tomasz Wróbel, Marcelo Capra, Jarosław Czyż, Shuhua Yi, Ki-Seong Eom, Anna Panovská, Wojciech Jurczak, Kamel Laribi, Lutz Jacobasch, Ross Baker, Richy Agajanian, Alejandro Berkovits, Muhıt Özcan, Stéphane Leprêtre, Catherine C. Coombs, Paula Cramer, Katharine L. Lewis, Marisa Hill, Katherine Bao, Yuanyuan Bian, Amy L. Stark, Ching Ching Leow, William G. Wierda · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-683 · 被引用次数：2 · 研究领域：Chronic Lymphocytic Leukemia Research、Phagocytosis and Immune Regulation、Lymphoma Diagnosis and Treatment

Abstract Introduction: Covalent Bruton tyrosine kinase inhibitors (cBTKi) are a mainstay of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment. Pirtobrutinib is a highly selective, non-covalent BTKi with proven efficacy in CLL/SLL patients (pts) previously treated with a cBTKi. We report results from the first head-to-head comparison of pirtobrutinib versus ibrutinib in treatment-naïve (TN) pts and pts with cBTKi-naive relapsed/refractory (R/R) CLL/SLL (NCT05254743). Methods: Eligible pts were randomized 1:1 to receive pirtobrutinib (200 mg QD) or ibrutinib (420 mg QD), stratified by del(17p) status and number of prior lines of therapy (0 vs 1 vs ≥ 2). Treatment was administered until progression or development of unacceptable toxicity. Primary endpoints were non-inferiority (NI) of overall response rate (ORR; partial response or better by independent review committee [IRC]/iwCLL 2018), in intent-to-treat (ITT) and R/R populations, with ORR ratio NI margins of 0.88 and 0.86, respectively. PFS was a secondary endpoint to be tested for superiority at a future timepoint. We present the final ORR analyses in ITT and R/R populations, and descriptive analyses of secondary endpoints, including in the TN population, using a 10June2025 data cut. Results: From 18August2022 to 17June2024, 662 pts were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331). For both arms, the median age was 67 (pirtobrutinib range, 39-90; ibrutinib, 34-86), and the medi...