Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Bispecific (GPRC5D×CD3)
Talquetamab
Talvey · TALQ
A GPRC5DxCD3 bispecific for myeloma with an emerging CRS-related acute kidney injury signal.
ModerateBispecific antibody (GPRC5DxCD3) · approved 2023
Relapsed or refractory multiple myeloma (after multiple prior lines of therapy)
Signature kidney injury
Prerenal / Hemodynamic AKI
Cytokine release syndrome is common with talquetamab (about three-quarters of patients in MonumenTAL-1, predominantly grade 1-2); CRS-associated acute kidney injury is an emerging, case-level signal that is not separately well quantified, superimposed on frequent baseline myeloma kidney disease.
Source: Chari et al., N Engl J Med 2022
Mechanism of kidney injury
T-cell activation triggers cytokine release (IL-6, IFN-gamma, TNF); CRS produces a prerenal, hemodynamic pattern (vasodilation, capillary leak, hypoperfusion) that may progress to ischemic acute tubular injury. Pre-existing myeloma kidney disease (cast nephropathy, light-chain tubulopathy, reduced GFR) increases susceptibility. Unlike BCMA agents, GPRC5D's distinct on-target effects are dermatologic/mucosal rather than renal.
Clinical presentation
Creatinine rise during CRS (fever, hypotension), often on a background of myeloma-related renal impairment; oliguria in severe cases. Note: talquetamab also causes prominent skin, nail, and oral (dysgeusia, dysphagia, weight loss) toxicities, which are non-renal but can drive reduced intake and secondary volume depletion.
Onset
Early, around step-up (priming) dosing and the initial full doses when CRS risk peaks.
Reversibility
Reversible
Anticancer mechanism
T-cell-redirecting bispecific antibody targeting GPRC5D (an orphan receptor highly expressed on malignant plasma cells) and CD3 on T cells, driving T-cell-mediated killing of myeloma cells. Used in relapsed/refractory multiple myeloma.
Management
Manage CRS by grade (supportive care, tocilizumab, corticosteroids) and maintain renal perfusion with fluids; hold dosing for severe CRS. Renal function generally recovers as CRS resolves; treat underlying myeloma kidney disease and address oral toxicity-related volume depletion concurrently.
Risk factors
- Higher-grade cytokine release syndrome
- Pre-existing myeloma-related CKD
- Volume depletion (including from oral toxicity/poor intake) and concurrent nephrotoxins
- High disease burden
Prevention
- Step-up (priming) dosing with premedication and monitoring per protocol
- Hydration and nutritional support given prominent oral toxicity; avoidance of additional nephrotoxins
- Serial renal-function monitoring during early dosing
Note · Renal injury is an emerging, CRS-mediated (indirect) signal rather than a direct nephrotoxic effect; quantitative renal data are limited for this newer agent and largely extrapolated from bispecific/CAR-T CRS-AKI literature.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment is established; talquetamab pharmacokinetics are not meaningfully renally dependent. Step-up dosing and holds for severe CRS, plus supportive management of oral toxicity, 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, not drug clearance.
Differential diagnosis
Distinguish CRS-driven prerenal/ischemic AKI from progression of underlying myeloma cast nephropathy (rising serum free light chains) and from volume depletion secondary to talquetamab's oral toxicity (poor intake, dysphagia). Timing with step-up dosing and CRS grade aids attribution.
Monitoring
- Vital signs and CRS grading during step-up and early full doses
- Serum creatinine/eGFR and electrolytes around dosing
- Weight, oral intake, and hydration status (prominent dysgeusia/dysphagia)
Key trials & series
- MonumenTAL-1 (Chari NEJM 2022) 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
- GPRC5D's signature toxicities are skin/nail/oral, not renal—but severe dysgeusia/dysphagia can cause prerenal AKI via poor intake.
- As with BCMA agents, AKI is mainly CRS hemodynamics on top of myeloma kidney disease.
- Step-up dosing and tocilizumab-based CRS management protect the kidney.
- Support nutrition and hydration aggressively given the oral toxicity profile.
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 (gprc5d×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.
LandmarkTalquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.Chari A et al. · N Engl J Med 2022 · PMID 36507686Pivotal MonumenTAL-1 study describing talquetamab 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 GPRC5D agents.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.PMIDCytokine release syndrome.Shimabukuro-Vornhagen A et al. · J Immunother Cancer 2018 · PMID 29907163Review of CRS pathophysiology and management underpinning CRS-associated AKI care.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.