Extracorporeal Free-Light-Chain Removal in Myeloma Cast Nephropathy: Plasma Exchange and Hemodialysis Strategies in the Era of Effective Antimyeloma Therapy

Abstract

Renal impairment affects up to half of patients with newly diagnosed multiple myeloma, and roughly 2–4% require dialysis at presentation, most often because of light-chain cast nephropathy. In these patients, renal recovery is associated with the speed and magnitude of serum free light-chain (sFLC) reduction in observational cohorts, an association that mainly reflects the hematologic response to chemotherapy; the incremental benefit of removing circulating sFLCs by extracorporeal means remains uncertain, and this narrative review is organized around that question in the current era of effective antimyeloma therapy. Plasma exchange was tested in three small randomized trials before proteasome inhibitors were available, the largest finding no benefit, and two randomized trials of high-cutoff hemodialysis on a bortezomib backbone, MYRE and EuLITE, found no benefit for their primary renal endpoints, with more pulmonary infections in the high-cutoff arm of EuLITE. Medium-cutoff membranes, polymethylmethacrylate adsorptive dialyzers, and hemodiafiltration with endogenous reinfusion have achieved substantial sFLC reduction with less albumin loss in small uncontrolled series, without any randomized comparison against conventional dialysis. Daratumumab-containing induction lowers sFLCs within days and may further narrow the residual rationale for enhanced clearance. Conventional high-flux hemodialysis combined with prompt antimyeloma therapy is therefore the evidence-based standard kidney-replacement modality when dialysis is indicated; the patient subsets in which a time-limited enhanced-removal strategy might still be tested are proposed as hypotheses for prospective trials, without validated thresholds.