In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll 3 additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ⩾partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ⩾stable disease. The most common adverse events (⩾grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.352.

中文翻译：

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口服方案ixazomib，pomalidomide和dexamethasone在复发/难治性多发性骨髓瘤中的I / II期试验。

在该I / II期试验中，对32来那度胺难治性多发性骨髓瘤（MM）给予了三联方案的ixazomib（Ixa：3或4 mg），pomalidomide（Pom：4 mg）和地塞米松（Dex：40 mg）耐心; 31位患者的反应和毒性可评估。剂量为1级（DL1，3 mg Ixa）时，有1/3的患者经历了3级疲劳，3级肺部感染，4级中性粒细胞减少和4级血小板减少。所有被认为是剂量限制的。根据3 + 3 I期设计，另外3例患者入选DL1，没有进一步的剂量限制性毒性（DLT）。在剂量水平2（DL2，4 mg Ixa）下，有1/3的患者出现了剂量限制性的发热性中性粒细胞减少，中性粒细胞减少和血小板减少（每个等级4级）。DL2扩大为3名没有进一步DLT的患者，确定了推荐的II期剂量（RP2D）。在第二阶段 RP2D治疗了另外19名患者。中位随访时间为11.9个月，有48％的患者达到了部分缓解（PR），其中5例（20％）的患者达到了很好的部分缓解（VGPR），其中76％的患者患有不稳定疾病。最常见的不良事件（2级）是贫血，中性粒细胞减少，血小板减少和感染。周围神经病变很少见。总之，Ixa / Pom / Dex是复发/难治性MM患者的良好耐受且有效的口服联合疗法。白血病于2017年12月18日在线接受文章预览。doi：10.1038 / leu.2017.352。和感染。周围神经病变很少见。总之，Ixa / Pom / Dex是复发/难治性MM患者的良好耐受且有效的口服联合疗法。白血病于2017年12月18日在线接受文章预览。doi：10.1038 / leu.2017.352。和感染。周围神经病变很少见。总之，Ixa / Pom / Dex是复发/难治性MM患者的良好耐受且有效的口服联合疗法。白血病于2017年12月18日在线接受文章预览。doi：10.1038 / leu.2017.352。