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

Hutchison, Colin A and Cockwell, Paul and Moroz, Veronica and Bradwell, Arthur R and Fifer, Lesley and Gillmore, Julian D and Jesky, Mark D and Storr, Markus and Wessels, Julie and Winearls, Christopher G and Weisel, Katja and Heyne, Nils and Cook, Mark (2019) High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial. The Lancet. Haematology, 6 (4). e217-e228. ISSN 2352-3026.

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Official URL: https://linkinghub.elsevier.com/retrieve/pii/S2352...

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).

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.

FUNDING

Gambro, Janssen, and Binding Site.

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
WJ Urogenital system. Urology
Divisions: Emergency Services > Renal
Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Beth Connors
Date Deposited: 02 Sep 2019 10:48
Last Modified: 02 Sep 2019 10:48
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2356

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