BRUIN CLL-321: Randomized Phase III Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab (IdelaR) or Bendamustine Plus Rituximab (BR) in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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, Shuhua Yi, Ru Feng, Vu Minh Hua, Jadwiga Holodja, Wojciech Jurczak, Matthias Ritgen, Lugui Qiu, Francesc Bosch, Catherine C. Coombs, Katherine Bao, Vishalkumar Patel, Bin Liu, Livia Compte, Ananya Guntur, Ying Wang, Marisa Hill, Ching Ching Leow, Paolo Ghia, Paul M. Barr · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-198147 · 被引用次数：20 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment

Background: Patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who relapse after treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) have limited effective treatment options. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that has shown promising safety and efficacy in pts with CLL/SLL after cBTKi therapy. Here we report results from the first randomized phase III study among CLL/SLL pts with relapsed/refractory disease who were all previously treated with cBTKi comparing pirtobrutinib versus investigators choice (IC) of IdelaR or BR (BRUIN CLL-321, NCT04666038). Methods: Eligible CLL/SLL pts previously treated with cBTKi were randomized 1:1 to receive pirtobrutinib monotherapy (200mg QD) or IC of IdelaR or BR and stratified by prior use of venetoclax and del(17p) status. The primary endpoint was progression free survival (PFS) assessed by independent review committee (IRC) per iwCLL2018 criteria. Secondary endpoints included investigator (INV) assessed PFS, event-free survival (EFS), time to next treatment (TTNT), overall survival (OS), and safety. Efficacy analyses were based on the intent to treat population. Crossover to pirtobrutinib arm was allowed after IRC confirmed disease progression (PD). The primary endpoint of PFS was met at primary analysis (29 Aug 2023 data cut). An updated analysis using a 09 Feb 2024 data cut is reported here. Further updates will be presented at the meeting. Results: 238 p...