High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial

Abstract

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). MethodsIn 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 high-flux haemodialysis (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 2year 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 pa...

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

“…Treatment of MM with bortezomibbased regimens became increasingly common after 2008 and the evidence in clinical and epidemiological studies for patients with MM and RI supports the benefits of this treatment 30,48 . The lack of association with extracorporeal removal of FLC is consistent with the major randomised controlled trials for plasma exchange and HCO-HD.in patients with MM and AKI 46,50,51 .…”

Light Chains With Heavy Effects

“…Two controlled trials in which all patients received a bortezomib-based multiple myeloma treatment showed no differences in the primary outcome of dialysis independence between the groups randomly assigned to receive high-cutoff hemodialysis and standard of care (high-flux hemodialysis). 17,18 Because of more effective chemotherapy and better supportive care, survival has improved for patients with multiple myeloma who need dialysis upon presentation, but the reduction in circulating FLCs still requires time, allowing the progression of kidney disease, which may occur rapidly. A deeper understanding of the monoclonal FLC-mediated mechanisms that lead to kidney injury may help in improving care.…”

Hemodiafiltration with ultrafiltrate regeneration reduces free light chains without albumin loss in multiple myeloma patients.

“…Furthermore, in a recent randomized clinical trial involving 98 patients with myeloma cast nephropathy on chemotherapy, the use of HCO hemodialysis compared with conventional hemodialysis did not result in a significant benefit with respect to hemodialysis dependence at 3 months [16]. Later, Hutchison et al shown that HCO hemodialysis was not associated with an improvement in renal recovery as compared with to High Flux-hemodialysis in patients with a new diagnosis of MM and myeloma cast nephropathy who received modified-dose bortezomib-containing chemotherapy although in both groups there was a sustained early reduction in serum FLC levels [17].…”