Department of Immunology and Inflammation and The Hugh and Josseline Langmuir Centre for Myeloma Research, Imperial College London, London, UK.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Blood Cancer J. 2022 Apr 1;12(4):52. doi: 10.1038/s41408-022-00626-4.
The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD (n = 58) and CD (n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9-1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.
来那度胺、沙利度胺和蛋白酶体抑制剂治疗后的复发多发性骨髓瘤患者中，口服伊沙佐米、环磷酰胺和地塞米松（ICD）联合方案具有良好的耐受性和疗效。我们开展了 MUKeight 研究，这是一项在先前接受来那度胺、沙利度胺和蛋白酶体抑制剂治疗的复发多发性骨髓瘤患者中开展的随机、对照、开放、平行分组、多中心 II 期研究，以评估 ICD 方案对比环磷酰胺和地塞米松（CD）方案在无进展生存期（PFS）方面的疗效，主要终点为 ICD 方案是否比 CD 方案具有更好的临床活性。该研究于 2016 年 1 月至 2018 年 12 月在英国 33 个中心入组 112 例患者，按 1:1 比例随机分配至 ICD 组（n=58）或 CD 组（n=54）。患者中位年龄 70 岁，中位接受过 4 线治疗。74%的患者被归类为虚弱。ICD 组的中位 PFS 为 5.6 个月，而 CD 组为 6.7 个月（风险比[HR]1.21，80%CI 0.9-1.6，p=0.3634）。两组的缓解率和总生存期无显著差异。ICD 组更常发生剂量调整或药物遗漏，以及严重不良事件（SAE）。综上，在 MUKeight 研究中入组的相对虚弱的患者中，添加伊沙佐米并未改善环磷酰胺和地塞米松的结局。
