Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Bispecific T-cell engager (gp100×CD3 ImmTAC)
Tebentafusp
Kimmtrak · Tebe
A gp100×CD3 ImmTAC whose renal risk is CRS-driven hypotension early in treatment — prerenal AKI.
ModerateBispecific T-cell engager (gp100×CD3 ImmTAC) · approved 2022
HLA-A*02:01-positive metastatic uveal melanoma
Signature kidney injury
Prerenal / Hemodynamic AKI
Cytokine release syndrome is very common early in treatment and, with the associated hypotension, is the principal mechanism of acute kidney injury; severe sepsis-like CRS with hypotension has been reported. The pivotal phase 3 trial established CRS, hypotension and rash as defining toxicities, mitigated by weekly step-up dosing. A dedicated tebentafusp renal/AKI study does not exist; renal injury is inferred from the CRS literature.
Source: Nathan et al., NEJM 2021 (pivotal phase 3); Geidel et al., JEADV 2023 (sepsis-like CRS case)
Mechanism of kidney injury
The renal pathway is hemodynamic/prerenal. T-cell redirection triggers a cytokine release syndrome (fever, vasodilatory hypotension, capillary leak) concentrated in the first doses, reducing renal perfusion and producing prerenal azotemia that can progress to ischemic tubular injury if hypotension is sustained. Weekly step-up dosing is designed to limit the cytokine peak. There is no characteristic intrinsic tubular or glomerular lesion; tumor lysis is not a prominent feature in this low-proliferative-burden disease.
Clinical presentation
Acute creatinine rise during a CRS episode — fever, hypotension, sometimes rash — typically with the first one to three weekly infusions. Prerenal indices and fluid responsiveness are usual. Cutaneous toxicity (rash, pruritus) is a common concurrent finding.
Onset
Early — first 1–3 weekly doses, coinciding with peak CRS.
Reversibility
Reversible
Anticancer mechanism
Bispecific gp100 peptide-HLA-directed T-cell engager (ImmTAC) that fuses an affinity-enhanced T-cell receptor recognizing a gp100 peptide presented on HLA-A*02:01 to an anti-CD3 effector domain, redirecting polyclonal T cells to kill gp100+ uveal melanoma cells. Approved for HLA-A*02:01-positive unresectable or metastatic uveal melanoma.
Management
Treat CRS-related hypotension promptly with IV fluids and supportive measures (vasopressors and corticosteroids for severe cases) to restore renal perfusion; hold/delay dosing per label for severe reactions. Prerenal AKI generally recovers once hemodynamics normalize.
Risk factors
- Higher-grade CRS / pronounced hypotension
- Pre-existing CKD or cardiovascular disease
- Volume depletion
- Concurrent nephrotoxins or antihypertensives amplifying hypotension
Prevention
- Mandatory weekly step-up dosing and monitored administration (inpatient for first doses per label)
- Pre-/post-infusion hydration and close blood-pressure monitoring
- Prompt treatment of hypotension
- Avoid concurrent nephrotoxins
Note · No tebentafusp-specific renal study exists; the CRS-driven hypotension to prerenal-AKI link is inferred from the pivotal trial and CRS case literature plus general onconephrology reviews. The renal risk is concentrated in the early step-up phase. Incidence is not quantified.
Clinical depth
Renal dose adjustment
No dedicated renal dose adjustment is established; the fixed weekly step-up schedule is driven by CRS mitigation, not renal function. Manage AKI by hemodynamic support rather than dose change.
Dialyzability & ESKD dosing
The engineered TCR-anti-CD3 fusion protein is not dialyzable in a clinically meaningful sense; no ESKD dose change is defined. Dialysis would support AKI management, not drug removal.
Differential diagnosis
CRS-driven prerenal/ischemic AKI (fever, hypotension, temporal link to early infusions, fluid-responsive) vs unrelated intrinsic renal disease; the early-dose CRS time-course is the key discriminator. There is no characteristic tebentafusp tubular/glomerular lesion.
Monitoring
- Blood pressure and temperature closely during and after each early infusion
- Serum creatinine around the step-up doses
- Volume status
- Skin toxicity assessment
Key trials & series
- Nathan NEJM 2021 — pivotal phase 3 (overall survival benefit)
- Hassel NEJM 2023 — 3-year overall-survival follow-up
Clinical pearls
- The renal danger window is the first few weekly doses — treat CRS hypotension early with fluids to protect perfusion.
- First doses are given under monitoring/inpatient observation precisely because of CRS hemodynamics.
- Tumor lysis is not a prominent concern in uveal melanoma — the mechanism here is hemodynamic.
- It is a fusion protein — no renal dosing or dialysis removal; renal incidence is not quantified.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of bispecific t-cell engager (gp100×cd3 immtac)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
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkOverall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma.Nathan P et al. · N Engl J Med 2021 · PMID 34551229Pivotal phase 3 establishing OS benefit and documenting CRS, hypotension and rash as defining toxicities.PMIDThree-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.Hassel JC et al. · N Engl J Med 2023 · PMID 37870955Long-term follow-up confirming durable OS and the CRS/cytokine-driven adverse-event profile.PMIDSepsis-like cytokine release syndrome after application of tebentafusp in metastasized uveal melanoma.Geidel G et al. · J Eur Acad Dermatol Venereol 2023 · PMID 38059699Case of severe CRS with hypotension — the mechanistic basis for CRS-driven prerenal AKI.PMIDConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Onconephrology reference for framing prerenal/CRS-mediated AKI mechanisms.
Related agents
Other agents sharing the same signature kidney injury.