Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
J Clin Oncol. 2021 Nov 10;39(32):3602-3612. doi: 10.1200/JCO.21.00443. Epub 2021 Aug 13.
Venetoclax is an oral BCL-2 inhibitor with single-agent activity in patients with relapsed or refractory multiple myeloma (RRMM) with t(11;14) translocation. Venetoclax efficacy in RRMM may be potentiated through combination with agents including bortezomib, dexamethasone, and daratumumab.
This phase I study (NCT03314181) evaluated venetoclax with daratumumab and dexamethasone (VenDd) in patients with t(11;14) RRMM and VenDd with bortezomib (VenDVd) in cytogenetically unselected patients with RRMM. Primary objectives included expansion-phase dosing, safety, and overall response rate. Secondary objectives included further safety analysis, progression-free survival, duration of response, time to progression, and minimal residual disease negativity.
Forty-eight patients were enrolled, 24 each in parts 1 (VenDd) and 2 (VenDVd). There was one dose-limiting toxicity in part 1 (grade 3 febrile neutropenia, 800 mg VenDd). Common adverse events with VenDd and VenDVd included diarrhea (63% and 54%) and nausea (50% and 50%); grade ≥ 3 adverse events were observed in 88% in the VenDd group and 71% in the VenDVd group. One treatment-emergent death occurred in part 2 (sepsis) in the context of progressive disease, with no other infection-related deaths on study with medians of 20.9 and 20.4 months of follow-up in parts 1 and 2, respectively. The overall response rate was 96% with VenDd (all very good partial response or better [≥ VGPR]) and 92% with VenDVd (79% ≥ VGPR). The 18-month progression-free survival rate was 90.5% (95% CI, 67.0 to 97.5) with VenDd and 66.7% (95% CI, 42.5 to 82.5) with VenDVd.
VenDd and VenDVd produced a high rate of deep and durable responses in patients with RRMM. These results support continued evaluation of venetoclax with daratumumab regimens to treat RRMM, particularly in those with t(11;14).
维奈托克是一种口服 BCL-2 抑制剂，对伴有 11 号染色体长臂断裂和 14 号染色体断裂易位（t[11;14]）的复发或难治性多发性骨髓瘤（RRMM）患者具有单药活性。维奈托克与硼替佐米、地塞米松和达雷妥尤单抗联合使用可能会增强 RRMM 的疗效。
这项 I 期研究（NCT03314181）评估了 t[11;14]RRMM 患者中维奈托克联合达雷妥尤单抗和地塞米松（VenDd）以及细胞遗传学未选择的 RRMM 患者中维奈托克联合硼替佐米（VenDVd）的疗效。主要研究目的包括扩展阶段的剂量、安全性和总体缓解率。次要研究目的包括进一步的安全性分析、无进展生存期、缓解持续时间、疾病进展时间和微小残留病灶阴性率。
共纳入 48 例患者，其中 24 例分别入组研究 1（VenDd）和研究 2（VenDVd）。研究 1 中出现 1 例剂量限制性毒性（3 级发热性中性粒细胞减少症，800mg VenDd）。VenDd 和 VenDVd 常见的不良反应包括腹泻（63%和 54%）和恶心（50%和 50%）；VenDd 组和 VenDVd 组分别有 88%和 71%的患者发生≥3 级不良反应。在研究中，有 1 例治疗相关死亡发生在研究 2 的疾病进展背景下（败血症），无其他感染相关死亡，在研究 1 和研究 2 中，分别有 20.9 和 20.4 个月的中位随访时间。VenDd 的总体缓解率为 96%（均为完全缓解或更好[≥非常好的部分缓解]），VenDVd 的总体缓解率为 92%（79%≥非常好的部分缓解）。VenDd 的 18 个月无进展生存率为 90.5%（95%CI，67.0 至 97.5），VenDVd 的 18 个月无进展生存率为 66.7%（95%CI，42.5 至 82.5）。
VenDd 和 VenDVd 在 RRMM 患者中产生了高深度和持久的缓解率。这些结果支持继续评估维奈托克联合达雷妥尤单抗方案治疗 RRMM，特别是针对伴有 t[11;14]的患者。
Zotero 插件
