Acalabrutinib plus venetoclax and rituximab in patients with treatment-naive (TN) mantle cell lymphoma (MCL): Results from the Phase 2 TrAVeRse study

作者：Eliza A. Hawkes, Joanna Romejko‐Jarosińska, Wojciech Jurczak, Sunil Iyengar, Abel Costa, Nimish Shah, Monique Menzies Wojtowicz, Allison Winter, Adam Witkowski, Neil Chua, Ana Jiménez Ubieto, John Kuruvilla, Diego Villa, Chan Y. Cheah, André Goy, Elise A. Chong, Andrew Wood, Rachel Fletcher, Stefanie Meyer, Rebecca Silva, Simon Rule, Michael Wang · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-884 · 被引用次数：12 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research

Abstract Introduction: MCL is a rare B-cell non-Hodgkin lymphoma typically treated with first-line (1L) chemoimmunotherapy (CIT). While Bruton tyrosine kinase inhibitors (BTKis) are approved in CIT combinations in TN MCL, novel 1L chemotherapy-free BTKi combinations are of interest. The phase 1b ACE-LY-106 study supported development of acalabrutinib, venetoclax, and rituximab (AVR) in patients (pts) with TN MCL (Wang et al. Blood Adv. 2024;8:4539-48). We report preliminary AVR efficacy and safety in TN MCL in the ongoing, open-label, phase 2 TrAVeRse study (NCT05951959). Methods: Pts were aged ≥18 y with TN MCL requiring treatment (tx), radiologically measurable disease, sufficient tissue for baseline clone detection for minimal residual disease (MRD) testing (clonoSEQ), and ECOG PS 0‒2 (or 3 if due to MCL). Pts received AVR induction (1 cycle [C] = 28 d): A (100 mg BID, C1‒C13 [+ C14 post induction]), V (C2‒C13, escalating during C2 [20 mg up to 400 mg daily]), and R (375 mg/m2 on day [D] 1 of C1‒12). Primary endpoint was MRD-negative (MRD-neg) complete response (CR) rate (MRD-neg in peripheral blood by next-generation sequencing [10-5; clonoSEQ], CR by 2014 Lugano criteria) at end of AVR induction (C13). Pts with MRD-neg CR at end of C13 were randomized 1:1 at C15D1 to continued A monotherapy until progressive disease (PD) or observation until PD with the option to restart A at relapse. Results: In total, 108 pts were enrolled and treated in 7 countries (January–July 2024)...