Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Bispecific (BCMA×CD3)
Teclistamab
Tecvayli · TECLI
A BCMAxCD3 bispecific for myeloma whose emerging renal signal is CRS-associated acute kidney injury on a background of myeloma kidney disease.
ModerateBispecific antibody (BCMAxCD3) · approved 2022
Relapsed or refractory multiple myeloma (after multiple prior lines, including triple-class exposure)
Signature kidney injury
Prerenal / Hemodynamic AKI
Cytokine release syndrome is very common with teclistamab (about 72% of patients in the pivotal MajesTEC-1 trial, predominantly grade 1-2); CRS-associated acute kidney injury is an emerging, case-level signal superimposed on frequent baseline myeloma-related kidney disease, and is not separately well quantified.
Source: Moreau et al., N Engl J Med 2022
Mechanism of kidney injury
T-cell activation drives cytokine release (IL-6, IFN-gamma, TNF); CRS causes hemodynamic (prerenal) renal hypoperfusion from vasodilation and capillary leak that can progress to ischemic acute tubular injury. Myeloma patients frequently have baseline cast nephropathy, light-chain proximal tubulopathy, and reduced GFR, which compound susceptibility; tumor lysis is generally less prominent than in acute leukemias.
Clinical presentation
Creatinine rise during CRS episodes (fever, hypotension, hypoxia), often superimposed on pre-existing myeloma-related kidney disease; oliguria in severe CRS. Concurrent infections (the dominant serious toxicity of BCMA bispecifics from hypogammaglobulinemia) can add septic AKI.
Onset
Early, concentrated around step-up (priming) dosing and the first full doses when CRS risk is highest (first days to weeks).
Reversibility
Reversible
Anticancer mechanism
T-cell-redirecting bispecific antibody binding B-cell maturation antigen (BCMA) on malignant plasma cells and CD3 on T cells, forming an immune synapse that triggers T-cell-mediated myeloma killing. Used in relapsed/refractory multiple myeloma.
Management
Manage CRS by grade (supportive care, tocilizumab for the IL-6 axis, corticosteroids) and support renal perfusion with fluids; hold dosing for severe CRS. Renal recovery typically parallels CRS resolution. Address underlying myeloma kidney disease (light-chain reduction, hydration) and treat intercurrent infection concurrently.
Risk factors
- Higher-grade cytokine release syndrome
- Pre-existing myeloma-related CKD/cast nephropathy
- Volume depletion and concurrent nephrotoxins
- High disease burden; intercurrent infection/sepsis
Prevention
- Mandatory step-up (priming) dosing with premedication (corticosteroid, antihistamine, antipyretic) to reduce CRS severity
- Inpatient or close monitoring during step-up dosing per protocol
- Hydration, avoidance of additional nephrotoxins, and infection prophylaxis; serial renal-function monitoring
Note · Renal toxicity is an emerging, indirect (CRS-mediated) signal rather than a direct nephrotoxic effect; quantitative renal data are limited for this newer agent and partly extrapolated from CAR-T/bispecific CRS-AKI cohorts.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment is established; teclistamab pharmacokinetics are not meaningfully renally dependent, and patients with renal impairment (including some on dialysis) have been treated. The operative levers are step-up dosing and holds for severe CRS 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, if used, treats AKI, not drug clearance.
Differential diagnosis
Distinguish CRS-driven prerenal/ischemic AKI (hypotension, capillary leak) from progression of underlying myeloma cast nephropathy/light-chain tubulopathy (rising serum free light chains, Bence-Jones proteinuria) and from septic AKI due to infection. Timing relative to 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
- Infection surveillance and immunoglobulin levels (hypogammaglobulinemia)
Key trials & series
- MajesTEC-1 (Moreau 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
- AKI here is usually CRS hemodynamics layered on pre-existing myeloma kidney disease—evaluate both.
- Step-up dosing with premedication is the key CRS- and AKI-mitigation strategy.
- Tocilizumab plus supportive care manages severe CRS; renal recovery tracks CRS resolution.
- Don't overlook infection: BCMA bispecifics cause profound hypogammaglobulinemia and septic AKI.
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.
LandmarkTeclistamab in Relapsed or Refractory Multiple Myeloma.Moreau P et al. · N Engl J Med 2022 · PMID 35661166Pivotal MajesTEC-1 trial reporting high rates of (mostly low-grade) CRS with teclistamab.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 engagers and other immunotherapies.PMIDNephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.Wen X et al. · Onco Targets Ther 2024 · PMID 39006885Onconephrology review specifically addressing renal toxicity of T-cell-engaging bispecific antibodies.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 showing CRS/ICANS grade as independent risk factors for mostly transient AKI after immune-effector-cell therapy.PMIDASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.Lee DW et al. · Biol Blood Marrow Transplant 2018 · PMID 30592986Current consensus CRS/ICANS grading framework guiding management of CRS-associated AKI.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2023 · PMID 38095483Onconephrology review addressing renal injury and mitigation with novel immunotherapies.
Related agents
Other agents sharing the same signature kidney injury.