Use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients. However, most MM patients eventually relapse and require salvage treatments. We report herein the result of a phase I/II study, performed from 2014 to 2017 to assess the feasibility and efficacy of a maximum tolerated dose (MTD) of lenalidomide (Len) combined with a fixed dose of once weekly subcutaneous (sc) 1.3 mg/m2 of bortezomib plus 20 mg of dexamethasone (scVRd regimen) in relapsed/refractory MM patients in the Japanese population. In the phase I part, dose-limiting toxicities were observed in three of six patients treated with 20 mg of Len; the MTD was accordingly defined as 15 mg in our cohort. In the phase II part, the recommended dose of the scVRD regimen showed a 71.4% best overall response rate, with a median overall survival of 14.8 months and a median progression-free survival of 8 months. Severe adverse events (≥ grade 3) were observed in ~ 15% of the patients, indicating the tolerability and efficacy of the regimen. Less prior treatment was associated with higher probability of durable response. This scVRd regimen may thus be a better fit for MM patients in early-stage relapse.

中文翻译：

---

硼替佐米、来那度胺和地塞米松治疗复发和难治性多发性骨髓瘤的 I/II 期研究。

使用包括蛋白酶体抑制剂和免疫调节药物在内的新型药物显着改善了多发性骨髓瘤 (MM) 患者的预后。然而，大多数 MM 患者最终会复发并需要抢救治疗。我们在此报告了一项 I/II 期研究的结果，该研究于 2014 年至 2017 年进行，以评估来那度胺 (Len) 的最大耐受剂量 (MTD) 与每周一次皮下 (sc) 1.3 的固定剂量相结合的可行性和有效性日本人群中复发/难治性 MM 患者的 mg/m2 硼替佐米加 20 mg 地塞米松（scVRd 方案）。在第一阶段，接受 20 mg Len 治疗的 6 名患者中有 3 名观察到剂量限制性毒性；因此，在我们的队列中，MTD 被定义为 15 mg。在 II 期部分，scVRD 方案的推荐剂量显示为 71。4% 的最佳总体缓解率，中位总体生存期为 14.8 个月，中位无进展生存期为 8 个月。在约 15% 的患者中观察到严重的不良事件（≥ 3 级），表明该方案的耐受性和有效性。较少的先前治疗与较高的持久反应概率相关。因此，这种 scVRd 方案可能更适合早期复发的 MM 患者。