Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Bispecific (BCMA×CD3)
Elranatamab
Elrexfio · ELRA
A BCMAxCD3 bispecific for myeloma whose emerging renal risk stems from cytokine release and, occasionally, tumor lysis.
ModerateBispecific antibody (BCMAxCD3) · approved 2023
Relapsed or refractory multiple myeloma (after multiple prior lines, including triple-class exposure)
Signature kidney injury
Prerenal / Hemodynamic AKI
Cytokine release syndrome is common with elranatamab (about 58% in the pivotal MagnetisMM-3 trial, largely grade 1-2 with the two-step priming regimen); CRS-associated acute kidney injury, and occasionally tumor-lysis-related injury, are emerging case-level signals that are not separately well quantified, superimposed on frequent myeloma kidney disease.
Source: Lesokhin et al., Nat Med 2023
Mechanism of kidney injury
T-cell activation drives cytokine release (IL-6, IFN-gamma, TNF); CRS produces hemodynamic (prerenal) hypoperfusion from vasodilation and capillary leak that can progress to ischemic acute tubular injury. Tumor lysis from rapid plasma-cell killing can add uric-acid/phosphate-mediated crystal and tubular injury; pre-existing myeloma kidney disease (cast nephropathy, light-chain tubulopathy) and infection (from BCMA-related hypogammaglobulinemia) compound risk.
Clinical presentation
Creatinine rise during CRS (fever, hypotension), sometimes with tumor-lysis metabolic derangements (hyperuricemia, hyperphosphatemia, hyperkalemia); often superimposed on baseline myeloma-related renal impairment, with septic AKI from intercurrent infection.
Onset
Early, concentrated around the two-step priming doses and the first full doses.
Reversibility
Reversible
Anticancer mechanism
Humanized BCMAxCD3 bispecific antibody that redirects T cells to kill BCMA-expressing myeloma cells via an immune synapse. Used in relapsed/refractory multiple myeloma.
Management
Manage CRS by grade (supportive care, tocilizumab, corticosteroids) and tumor lysis aggressively (hydration, rasburicase/allopurinol, electrolyte correction, renal replacement if needed); hold dosing for severe CRS. Renal recovery generally follows control of the underlying syndrome; treat myeloma kidney disease and infection concurrently.
Risk factors
- Higher-grade cytokine release syndrome
- Pre-existing myeloma-related CKD/cast nephropathy
- High disease burden (CRS and tumor-lysis risk)
- Volume depletion, intercurrent infection, and concurrent nephrotoxins
Prevention
- Two-step (priming) dosing with premedication and monitoring per protocol
- Tumor-lysis prophylaxis (hydration, uric-acid-lowering therapy) in high-burden disease; infection prophylaxis
- Hydration, avoidance of additional nephrotoxins, and serial renal monitoring
Note · Renal injury is an emerging, indirect (CRS/TLS-mediated) signal rather than a direct nephrotoxic effect; quantitative renal data remain limited for this newer agent and are partly extrapolated from bispecific/CAR-T CRS-AKI cohorts.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment is established; elranatamab pharmacokinetics are not meaningfully renally dependent. Two-step priming dosing and holds for severe CRS, plus TLS prophylaxis, are the operative levers rather than renal dose modification.
Dialyzability & ESKD dosing
Not dialyzable—an IgG-based bispecific antibody cleared by catabolism; not removed by hemodialysis and no supplemental dosing needed. Renal replacement therapy treats AKI/TLS, not drug clearance.
Differential diagnosis
Separate CRS-driven prerenal/ischemic AKI from TLS crystal/urate nephropathy (hyperuricemia/hyperphosphatemia), from progression of myeloma cast nephropathy (rising free light chains), and from septic AKI. Timing with priming doses, CRS grade, and the tumor-lysis lab signature guide attribution.
Monitoring
- Vital signs and CRS grading during priming and early full doses
- Tumor lysis labs and serum creatinine/eGFR around initiation in high-burden disease
- Infection surveillance and immunoglobulin levels (hypogammaglobulinemia)
Key trials & series
- MagnetisMM-3 (Lesokhin Nat Med 2023) registrational trial
- Wen Onco Targets Ther 2024 bispecific-antibody nephrotoxicity review
- Leon-Roman Clin Kidney J 2024 immune-effector-cell AKI cohort (analogous CRS-AKI)
Clinical pearls
- Among the myeloma bispecifics, elranatamab carries a more explicit tumor-lysis as well as CRS-AKI signal—give TLS prophylaxis in high burden.
- AKI is usually CRS hemodynamics layered on myeloma kidney disease, not direct tubular toxicity.
- Two-step priming with premedication mitigates CRS and downstream AKI.
- Watch for septic AKI from BCMA-related hypogammaglobulinemia and infection.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Prerenal / Hemodynamic AKIAcute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of bispecific (bcma×cd3)s.
Immune / Infusion
CRS, infusion reactions, irAEs, anaphylaxis
- Cytokine release syndrome
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- ICANS / neurotoxicity
Hematologic
Cytopenias, thrombosis, TMA
- Cytopenias, hypogammaglobulinemia
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkElranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.Lesokhin AM et al. · Nat Med 2023 · PMID 37582952Pivotal MagnetisMM-3 trial describing elranatamab efficacy and its cytokine release syndrome profile.PMIDAcute Kidney Injury in Cancer Immunotherapy Recipients.Joseph A et al. · Cells 2022 · PMID 36552755Review of CRS- and TLS-mediated AKI with bispecific T-cell-engaging antibodies.PMIDNephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.Wen X et al. · Onco Targets Ther 2024 · PMID 39006885Onconephrology review of renal toxicity of T-cell-engaging bispecific antibodies including BCMA agents.PMIDThe tumor lysis syndrome.Howard SC et al. · N Engl J Med 2011 · PMID 21561350Authoritative TLS review relevant to elranatamab's tumor-lysis-associated renal injury.PMIDTransient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies.Leon-Roman J et al. · Clin Kidney J 2024 · PMID 38500492Cohort linking CRS/ICANS grade to mostly transient AKI after immune-effector-cell therapy.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2023 · PMID 38095483Onconephrology review of renal injury and mitigation with novel immunotherapies.
Related agents
Other agents sharing the same signature kidney injury.