Pirtobrutinib in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Final update from the Phase 1/2 BRUIN study

作者：Michael Wang, Jonathon B. Cohen, Nirav N. Shah, Wojciech Jurczak, Pier Luigi Zinzani, Chan Y. Cheah, Chaitra S. Ujjani, Youngil Koh, Won Seog Kim, Sunita D. Nasta, Ian W. Flinn, Benoît Tessoulin, Shuo Ma, Alvaro J. Alencar, David Lewis, Jennifer A. Woyach, Kami J. Maddocks, Krish Patel, Yucai Wang, Joanna Rhodes, Constantine S. Tam, John F. Seymour, Hirokazu Nagai, Julie Vose, Bita Fakhri, Marc Hoffmann, Francisco J. Hernandez‐Ilizaliturri, Andrew D. Zelenetz, Anita Kumar, Talha Munir, Donald E. Tsai, Paolo Abada, Minna Balbas, Li J, Ying Wang, Lindsey E. Roeker, Toby A. Eyre · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-665 · 被引用次数：6 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research

Abstract Background: Despite the efficacy of covalent Bruton tyrosine kinase inhibitors (cBTKi) in R/R MCL, patients (pts) ultimately discontinue treatment due to intolerance or development of resistance and disease relapse. Pirtobrutinib is a highly selective, non-covalent BTKi that inhibits BTK with low nM potency throughout the daily dosing interval. Pirtobrutinib was safe and effective in the phase 1/2 BRUIN study in pts with R/R B-cell malignancies, including those previously treated with a BTKi. Pirtobrutinib is approved in the EU for adults with R/R MCL after prior treatment with a BTKi (EMA Conditional Approval, Oct 2023), and in the USA for adults with R/R MCL after ≥ 2 lines of systemic therapy, including a BTKi (FDA Accelerated Approval, Jan 2023).Here, we report the final results from the phase 1/2 BRUIN study (NCT03740529), with a follow-up period of up to 5 yrs, focusing on the efficacy and safety of pirtobrutinib in all R/R MCL pts. Methods: Pts with R/R MCL who received ≥1 prior lines of therapy (including BTKi) were eligible for treatment with pirtobrutinib monotherapy. Key endpoints included overall response rate (ORR), duration of response (DOR) and progression-free survival (PFS), all assessed by independent review committee (IRC) per Lugano 2014 criteria (presented here) and investigator, overall survival (OS), and safety. Pts were included across the range of doses evaluated in dose escalation and expansion (25-300 mg/day). A data cutoff on 27 January 20...