Dana-Farber Cancer Institute, Boston, MA, USA.
Ohio State University, Columbus, OH, USA.
Br J Haematol. 2018 Jul;182(2):231-244. doi: 10.1111/bjh.15394. Epub 2018 Jun 25.
Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM; 64 patients were enrolled across both phases. Patients received twice-weekly oral ixazomib 3·0 or 3·7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with twice-weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 1; the RP2D was 3·0 mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% ≥very good partial response; 24% complete response). Median progression-free survival was 24·9 months. Responses (median duration 36·9 months for patients receiving the RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity with promising long-term outcomes in NDMM patients but may be associated with greater toxicity compared with weekly ixazomib-Rd in this setting.
每周一次来那度胺联合地塞米松（Rd）在新诊断的多发性骨髓瘤（NDMM）患者中是可行的，并且已经显示出疗效。这项 1/2 期研究（NCT01383928）评估了每周两次来那度胺联合地塞米松在 NDMM 中的推荐 2 期剂量（RP2D）、药代动力学、安全性和疗效；两个阶段共招募了 64 名患者。患者接受每周两次口服来那度胺 3·0 或 3·7mg 联合来那度胺 25mg 和地塞米松 20mg（第 9-16 周期为 10mg），最多 16 个 21 天周期，随后单独用每周两次来那度胺维持治疗。在第 1 周期未报告剂量限制毒性；根据多个周期的总体耐受性，RP2D 为 3·0mg。在 62 名可评估患者中，确认的总体缓解率为 94%（68%为非常好的部分缓解；24%为完全缓解）。中位无进展生存期为 24.9 个月。在治疗期间，反应（接受 RP2D 的患者的中位缓解持续时间为 36.9 个月）加深。3 级药物相关不良事件（AE）发生在 64%的患者中，包括皮疹，13%；周围神经病变，8%；高血糖症，8%。无 4 级药物相关 AE。由于 AE，有 13 名患者停药。每周两次来那度胺联合地塞米松在 NDMM 患者中具有显著的活性和良好的长期疗效，但与该方案中的每周一次来那度胺联合地塞米松相比，可能与更大的毒性相关。
