High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial
High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial
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DOI：
10.1016/s2352-3026(19)30014-6
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发表时间：
2019-04-01
影响因子：
24.7
通讯作者：
Cook, Mark
中科院分区：
文献类型：
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作者：
Hutchison, Colin A.;Cockwell, Paul;Cook, Mark
背景在多发性骨髓瘤中，由血清中致病性游离轻链免疫球蛋白引起的骨髓瘤管型肾病引起的严重急性肾损伤。高截留量血液透析（HCO-HD）可清除血清中大量游离轻链免疫球蛋白，但其对临床结局的影响尚不确定。因此，我们的目的是评估HCO-HD是否可以增加与标准高通量血液透析（HF-HD）治疗相比，新发多发性骨髓瘤，严重急性肾损伤和骨髓瘤管型肾病患者的肾恢复频率。和急性肾损伤，需要在英国和德国的16家医院的肾脏服务透析。通过随机数字生成将患者随机分配（1：1）接受强化HCO-HD（疗程持续6-8小时）或标准HF-HD，并按年龄和中心对其进行分层。患者和治疗他们的医务人员对治疗分配不设盲。患者接受硼替佐米、阿霉素和地塞米松化疗，然后随访2年。主要结局是随机分组后90天的透析独立性，在意向治疗人群中进行评估。该试验已完成随访，并在ISRCTN注册处注册，编号ISRCTN 45967602。结果在2008年6月7日至2013年9月18日期间，我们招募了90名患者，其中43名（48%）被随机分配接受HCO-HD，47名（52%）被随机分配接受HF-HD。所有90例患者均纳入主要结局分析。HF-HD组1例（2%）患者在接受治疗前撤回知情同意书。治疗期间，HCO-HD组9例（21%）患者和HF-HD组2例（4%）患者中止试验治疗。90天后，HCO-HD组24例（56%）患者和HF-HD组24例（51%）患者独立于透析（相对风险1 . 09，95% CI 0 . 74-1 . 61; p= 0。81）。在2年随访期间，HCO-HD组报告了98起严重不良事件，HF-HD组报告了82起严重不良事件。最常见的严重不良事件是感染以及与心血管、血栓形成和肌肉骨骼系统相关的不良事件。在最初的90天内，HCO-HD组报告了26例感染，HF-HD组报告了13例感染，其中HCO-HD组14例肺部感染，HF-HD组3例肺部感染。解释在这项2期研究中HCO-HD未改善因急性肾衰竭需要血液透析的新发多发性骨髓瘤和骨髓瘤管型肾病患者的临床结局与接受HF-HD的患者相比，接受硼替佐米为基础的化疗方案。这些结果不支持在这些患者中进行HCO-HD的III期研究。
Background In multiple myeloma, severe acute kidney injury due to myeloma cast nephropathy is caused by pathogenic free light chain immunoglobulin in serum. High cutoff haemodialysis (HCO-HD) can remove large quantities of free light chain immunoglobulin from serum, but its effect on clinical outcomes is uncertain. We therefore aimed to assess whether HCO-HD could increase the frequency of renal recovery in patients with de novo multiple myeloma, severe acute kidney injury, and myeloma cast nephropathy relative to treatment with standard high-flux haemodialysis (HF-HD).Methods In this open-label, phase 2, multicentre, randomised controlled trial (EuLITE), we recruited patients with newly diagnosed multiple myeloma, biopsy-confirmed cast nephropathy, and acute kidney injury that required dialysis from renal services in 16 hospitals in the UK and Germany. Patients were randomly assigned (1:1) by random number generation to receive intensive HCO-HD (in sessions lasting 6-8 h) or standard HF-HD and they were stratified by age and centre. Patients and the medical staff treating them were not masked to treatment allocation. Patients received bortezomib, doxorubicin, and dexamethasone chemotherapy, and were then followed up for 2 years. The primary outcome was independence from dialysis at 90 days after random allocation to groups, which was assessed in an intention-to-treat population. The trial has completed follow-up, and is registered at the ISRCTN registry, number ISRCTN45967602.Findings Between June 7, 2008, and Sept 18, 2013, we recruited 90 patients, of whom 43 (48%) were randomly assigned to receive HCO-HD and 47 (52%) were randomly assigned to receive HF-HD. All 90 patients were included in the analysis of the primary outcome. One (2%) patient from the HF-HD group withdrew consent before receiving treatment. During treatment, nine (21%) patients from the HCO-HD group and two (4%) patients in the HF-HD group discontinued trial treatment. After 90 days, 24 (56%) patients in the HCO-HD group and 24 (51%) patients in the HF-HD group were independent from dialysis (relative risk 1 . 09, 95% CI 0 . 74-1 . 61; p= 0 . 81). During the 2-year follow-up, 98 serious adverse events were reported in the HCO-HD group and 82 serious adverse events were reported in the HF-HD group. The most common serious adverse events were infections and adverse events related to the cardiovascular and thrombotic and musculoskeletal systems. During the first 90 days, 26 infections were reported in the HCO-HD group and 13 infections were reported in the HF-HD group, including 14 lung infections in the HCO-HD group and three lung infections in the HF-HD group.Interpretation In this phase 2 study, HCO-HD did not improve clinical outcomes for patients with de novo multiple myeloma and myeloma cast nephropathy who required haemodialysis for acute kidney injury and who received a bortezomib-based chemotherapy regimen relative to those receiving HF-HD. These results do not support proceeding to a phase 3 study for HCO-HD in these patients.