Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Tumor-infiltrating lymphocyte (TIL) therapy
Lifileucel
Amtagvi · LIFI
A one-time tumor-infiltrating-lymphocyte product whose kidney risk lives in the IL-2 conditioning, not the cells.
ModerateTumor-infiltrating lymphocyte (TIL) cell therapy · approved 2024
Unresectable or metastatic melanoma (post anti-PD-1)
Signature kidney injury
Prerenal / Hemodynamic AKI
AKI is common in the overall regimen but is driven by the high-dose IL-2 component (and lymphodepletion), not the TILs themselves. In the pooled C-144-01 experience renal/AKI events fell within the expected high-dose IL-2 toxicity spectrum; a clean drug-specific AKI rate for the TIL product alone is not established. By analogy to other adoptive cell therapies, AKI in the broader CAR-T literature runs 5-33%.
Source: Chesney et al., J Immunother Cancer 2022
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Distal Tubule / Collecting Duct
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
High-dose IL-2 causes a systemic capillary-leak syndrome: cytokine-mediated vascular endothelial permeability produces intravascular volume depletion, hypotension and prerenal hemodynamic AKI that can progress to ischemic acute tubular necrosis. Lymphodepleting fludarabine/cyclophosphamide adds direct tubular and prerenal stress; rapid tumor kill can trigger tumor-lysis metabolic derangements; cytokine release and sepsis from neutropenia contribute additional ischemic injury.
Clinical presentation
Oliguria, weight gain and edema with hypotension during IL-2 dosing; rising creatinine, low fractional excretion of sodium early (prerenal) evolving to ATN with muddy-brown granular casts if ischemia persists; electrolyte derangements and, with tumor lysis, hyperuricemia/hyperphosphatemia/hyperkalemia.
Onset
Acute — within hours to days of high-dose IL-2 administration during the conditioning/expansion phase.
Reversibility
Reversible
Anticancer mechanism
Autologous tumor-infiltrating lymphocytes (TILs) expanded ex vivo and reinfused after non-myeloablative lymphodepletion (fludarabine/cyclophosphamide), followed by high-dose bolus interleukin-2 (IL-2) to support TIL persistence. Approved for advanced melanoma after progression on a PD-1 inhibitor (and BRAF-targeted therapy if BRAF-mutant).
Management
Supportive intensive care: judicious fluids and vasopressors for capillary-leak hypotension, hold further IL-2 doses, treat ischemic ATN supportively, and apply standard tumor-lysis measures if metabolic derangements appear. AKI is usually reversible as IL-2 effects resolve; renal replacement therapy is rarely needed.
Risk factors
- Number/intensity of high-dose IL-2 doses tolerated
- Capillary-leak-driven hypotension
- Baseline CKD, older age, cardiovascular disease
- Lymphodepleting fludarabine/cyclophosphamide and nephrotoxic antimicrobials
Prevention
- Treat only in centers experienced with high-dose IL-2
- Careful fluid and pressor management during capillary leak
- Stop IL-2 doses for evolving organ dysfunction
- Tumor-lysis prophylaxis and close renal/electrolyte monitoring through conditioning
Note · The renal risk is essentially that of high-dose IL-2 and lymphodepletion, well described historically, rather than a novel property of the TIL cells. Class/regimen-based reasoning; the immunotherapy and CAR-T nephrotoxicity reviews are cited for the IL-2/cell-therapy mechanisms.
Clinical depth
Renal dose adjustment
Lifileucel itself is a one-time cell infusion with no renal dose adjustment. The renal-relevant levers are the conditioning regimen: fludarabine requires dose reduction in renal impairment (it is renally cleared and accumulates), and high-dose IL-2 dosing is governed by real-time hemodynamic/organ tolerance rather than a fixed CrCl threshold.
Dialyzability & ESKD dosing
The TIL product is not dialyzable. Among conditioning agents, fludarabine's active metabolite is partly dialyzable but timing is not standardized; IL-2 management is hemodynamic. No established protocol exists for the regimen in dialysis-dependent patients, who are generally excluded.
Differential diagnosis
Separate IL-2 capillary-leak prerenal AKI / ATN (hypotension, edema, capillary leak) from tumor-lysis AKI (urate/phosphate, early), fludarabine tubular effect, and neutropenic-sepsis ATN. The pattern and timing relative to IL-2 dosing usually identify the dominant mechanism.
Monitoring
- Hourly-to-daily creatinine, urine output and weight during IL-2
- Blood pressure and volume status (capillary leak surveillance)
- Electrolytes, uric acid and phosphate (tumor-lysis screen) at conditioning
- Markers of neutropenic sepsis as a competing AKI cause
Key trials & series
- C-144-01 pooled cohorts (Chesney, J Immunother Cancer 2022) — registrational safety dataset
- Sarnaik JCO 2021 — initial efficacy/safety report describing the IL-2 regimen
Clinical pearls
- The kidney risk is the regimen (high-dose IL-2 + lymphodepletion), not the TIL cells.
- IL-2 AKI is the textbook capillary-leak prerenal-to-ATN sequence and is usually reversible if IL-2 is stopped.
- Don't forget to renally dose-reduce fludarabine — it accumulates and adds tubular toxicity.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIAcute Tubular NecrosisElectrolyte Wasting
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkLifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma.Sarnaik AA et al. · J Clin Oncol 2021 · PMID 33979178Key efficacy/safety report; describes the high-dose IL-2 regimen that drives the hemodynamic AKI risk.PMIDEfficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study.Chesney J et al. · J Immunother Cancer 2022 · PMID 36600653Pooled safety analysis; renal/AKI events appear within the expected high-dose IL-2 toxicity spectrum.LandmarkNephrotoxicity of Cancer Immunotherapies: Past, Present and Future.Perazella MA et al. · J Am Soc Nephrol 2018 · PMID 29959196Onconephrology review covering high-dose IL-2 capillary-leak AKI — the mechanistic basis for the conditioning-related renal risk.PMIDAcute kidney injury following CAR-T cell therapy: a nephrologist's perspective.Kanbay M et al. · Clin Kidney J 2024 · PMID 39781479Nephrology review of adoptive cell-therapy AKI (incidence 5-33%, CRS/TLS/lymphodepletion mechanisms) — directly analogous to TIL therapy.PMIDNephrotoxicity in CAR-T Cell Therapy.Sadowski K et al. · Transplant Cell Ther 2025 · PMID 40107382Reviews AKI/CKD mechanisms, risk factors and lymphodepletion safety in cell therapy — supports the conditioning-driven renal framing.PMIDTumour lysis syndrome.Howard SC et al. · Nat Rev Dis Primers 2024 · PMID 39174582Authoritative TLS review supporting the tumor-lysis component of cell-therapy-associated AKI.
Related agents
Other agents sharing the same signature kidney injury.