这项 1b 期研究 (NCT02717624) 评估了 acalabrutinib、venetoclax 和 rituximab (AVR) 在初治套细胞淋巴瘤 (TN MCL) 中的安全性和有效性。患者从第 1 周期开始接受 acalabrutinib（阿卡拉布替尼）治疗，直至疾病进展或过度毒性；利妥昔单抗治疗 6 个周期，并在第 24 周期内每隔一个周期进行维持治疗或直至疾病进展；以及 Venetoclax（从第 2 周期开始）治疗 24 个周期。 21 名患者入组，95.2% 完成诱导（6 个 AVR 周期），47.6% 继续使用 acalabrutinib 维持治疗。 13 名 (61.9%) 患者出现 3-4 级不良事件 (AE)，最常见的是中性粒细胞减少症 (33.3%)。 7 例 (33.3%) 患者感染了 COVID-19（6 例 [28.6%] 例严重 AE；5 例 [23.8%] 死亡，全部为未接种疫苗的患者）。没有发生≥3级的心房颤动、室性快速心律失常、大出血或肿瘤溶解综合征事件。根据卢加诺标准，总缓解率 (ORR) 为 100%（95% 置信区间 [CI]：83.9, 100.0），完全缓解 (CR) 为 71.4%。中位随访时间为 27.8 个月，但尚未达到中位无进展生存期 (PFS) 和总生存期 (OS)。 1 年和 2 年的 PFS 率分别为 90.5% (95% CI: 67.0, 97.5) 和 63.2% (34.7, 82.0)；在审查了 COVID-19 死亡人数后，两者均为 95%。 1 年和 2 年 OS 率分别为 95.2% (95% CI: 70.7, 99.3) 和 75.2% (50.3, 88.9)；在审查了 COVID-19 死亡人数后，两者均为 100%。总体而言，87.5% 具有可用微小残留病 (MRD) 数据的患者在治疗期间达到 MRD 阴性（10-6；下一代测序）。 AVR 代表 TN MCL 的免化疗方案，可带来高 ORR 和高 MRD 阴性率。版权所有 © 2024 美国血液学会。

This phase 1b study (NCT02717624) evaluated the safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until progressive disease, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled, 95.2% completed induction (6 AVR cycles), and 47.6% continued maintenance with acalabrutinib. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs; 5 [23.8%] deaths, all among unvaccinated patients). There were no grade ≥ 3 events of atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) by Lugano criteria was 100% (95% confidence interval [CI]: 83.9, 100.0) with 71.4% complete response (CR). With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI: 67.0, 97.5) and 63.2% (34.7, 82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI: 70.7, 99.3) and 75.2% (50.3, 88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10-6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity.Copyright © 2024 American Society of Hematology.