Treatment of Myeloma Cast Nephropathy (MCN): A Randomized Trial Comparing Intensive Haemodialysis (HD) with High Cut-Off (HCO) or Standard High-Flux Dialyzer in Patients Receiving a Bortezomib-Based Regimen (the MYRE Study, by the Intergroupe Francophone du Myélome (IFM) and the French Society of Nephrology (SFNDT))

Multiple myeloma (MM) is often revealed by acute kidney injury (AKI) usually related to MCN. Recovery of renal function is a key prognostic factor. With novel anti-myeloma agents, HD-independence occurs in about 30% of pts with severe AKI, advocating for the use of additional strategies to rapidly remove circulating monoclonal free light chains (FLC).

We designed a prospective randomized trial to compare the HD-independence rate in pts with inaugural severe AKI secondary to biopsy-proven MCN, treated by intensive HD (8 sessions over the first 10 days, then thrice a week) using either a HCO dialyzer or a conventional high-flux dialyzer. In both groups, pts received 21-day courses of Bortezomib and dexamethasone (BD), reinforced by cyclophosphamide after 3 cycles in the absence of haematological response (HR).

Between 2011 and 2015, 98 pts were randomised. One pt withdrew consent, and 3 had main exclusion criteria. Baseline characteristics in the control arm (n=48) and HCO arm (n=46) were close, including similarly high serum FLC levels (median 6,015mg/L).

HD independence was achieved in 33% and 43% (p= 0.31) at 3 and in 37.5% and 60 % (p=0.03) at 6 mo, in the control and HCO arms, respectively. HR rate of very good partial response or above at 3 mo based on FLC was 48% in control and 59% in HCO groups (p=0.29). Tolerance of HD schedule and of chemotherapy was acceptable in both arms. At 12 mo, 17 pts have died (10 vs 7).

This randomized trial demonstrates that in MM patients with MCN and severe AKI treated with a bortezomib-based regimen, intensive HCO-HD results in higher renal recovery rate than HD with conventional high-flux dialyzers.