Myeloma kidney (cast nephropathy) results from excess monoclonal free light chains and demands rapid, deep reduction of those light chains to allow renal recovery. Modern regimens are tailored to maximize both hematologic and renal responses, including in patients with severe renal impairment or on dialysis.
Rapid light-chain reduction
Prompt therapy is essential. Bortezomib-based regimens (often with daratumumab) remain the frontline choice for rapid free-light-chain reduction, with intravenous bortezomib favored in severe renal injury and high-dose dexamethasone given acutely. Autologous stem-cell transplantation is feasible with dose-adjusted conditioning.
Immunotherapy across the disease course
Anti-CD38 antibodies (daratumumab, isatuximab) are highly effective, including in moderate-to-severe renal impairment and on dialysis. Bispecific antibodies (teclistamab, elranatamab, talquetamab) and CAR-T cell therapies (ciltacabtagene and idecabtagene) achieve high response rates in advanced disease — with growing evidence of efficacy even in renal impairment — and are moving into earlier lines; cytokine release syndrome, neurotoxicity, and (with CAR-T) acute kidney injury during CRS require attention. Belantamab mafodotin, a BCMA-directed antibody-drug conjugate, has had a notable arc: withdrawn from the US market in 2022, it was re-approved in October 2025 in combination with bortezomib and dexamethasone after the DREAMM-7 and DREAMM-8 trials showed superior progression-free and overall survival versus standard triplets; ocular toxicity (keratopathy) remains its defining risk and is managed under a REMS. Oral cereblon-modulating agents (iberdomide, mezigdomide) add further options in heavily pretreated disease.
Transplantation and supportive care
Kidney transplantation is possible for selected patients in deep, durable remission, with individualized, multidisciplinary care. High-cutoff dialysis does not improve outcomes and is not standard. All patients need full evaluation of light chains and renal function at diagnosis and follow-up.
| Class | Renal applicability | Key point |
|---|---|---|
| Bortezomib-based (± daratumumab) | Frontline | Best renal-response data; rapid FLC reduction |
| Anti-CD38 antibodies | Effective in CKD/dialysis | Daratumumab, isatuximab |
| Bispecifics / CAR-T | Efficacy incl. renal impairment | CRS, neurotoxicity, AKI risk |
| Belantamab mafodotin | Relapsed/refractory | Re-approved 2025 (DREAMM-7/8); ocular toxicity |
Further reading: monoclonal antibodies in myeloma kidney (Derudas & Chiriu, 2024); DREAMM-7 and DREAMM-8 belantamab combinations (2024–2025); bispecific/CAR-T consensus (Ludwig et al., Lancet Oncology 2023).