Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor–Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)

作者：Jeff P. Sharman, Talha Munir, Sebastian Grosicki, Lindsey E. Roeker, John M. Burke, Christine I. Chen, Norbert Grząśko, George Follows, Zoltán Mátrai, Alessandro Sanna, Lugui Qiu, Ru Feng, Vu Minh Hua, Wojciech Jurczak, Matthias Ritgen, Shuhua Yi, Francesc Bosch, Catherine C. Coombs, Katherine Bao, Vishalkumar Patel, Bin Liu, Livia Compte, Ananya Guntur, Denise Y. Wang, Marisa Hill, Ching Ching Leow, Paolo Ghia, Paul M. Barr · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-00166 · 被引用次数：41 · 研究领域：Chronic Lymphocytic Leukemia Research、Phagocytosis and Immune Regulation、Lymphoma Diagnosis and Treatment

PURPOSE Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR). METHODS Patients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee–assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024). RESULTS A total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75]; P = .0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75]; P = .7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 7...