How should kidney function be monitored during Lifileucel therapy?

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.

How can kidney injury from Lifileucel be prevented?

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 through conditioning

Who is at higher risk of kidney injury from Lifileucel?

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.

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Printable monograph

Tumor-infiltrating lymphocyte (TIL) therapy

Lifileucel

Amtagvi · LIFI

Tumor-infiltrating lymphocyte (TIL) therapy · approved 2024 · 6 citations · FAERS AKI reporting ROR 12.48 (95% CI 8.06–19.31, 22 AKI reports)

Up to date· through 2025

Fairly sourced6/9 · 6 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 7y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
Met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

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

Unresectable or metastatic melanoma (post anti-PD-1)

§01

Signature kidney injury

Signature lesion

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

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Within hours to days of the high-dose IL-2 given during conditioning/expansion.

Distilled from: “Acute — within hours to days of high-dose IL-2 administration during the conditioning/expansion phase.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityReversible

Evidence6 citations

Nephron map

Vasculature / Endothelium

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.

§03

Kidney injury

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.

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.Lesion-level management framework

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 through conditioning

Anticancer mechanism· how it treats cancer

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).

Note · Class/regimen-based reasoning; the immunotherapy and CAR-T nephrotoxicity reviews are cited for the IL-2/cell-therapy mechanisms.

§04

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) 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.

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2018–2025 · 3 since 2023

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Oct 2025) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: TREATMENT-RELATED MORTALITY, PROLONGED SEVERE CYTOPENIA, SEVERE INFECTION, CARDIOPULMONARY and RENAL IMPAIRMENT Monitor patients for prolonged severe cytopenia and monitor for internal organ hemorrhage [see Warnings and Precautions (5.1 , 5.2 , 5.3) ]. Administer filgrastim or a biosimilar product to patients beginning Day 1 after AMTAGVI and continuing daily until the absolute neutrophil count (ANC) is greater than 1000 per mm 3 for 3 consecutive days, or per institutional standard. Treat severe infections [see Warnings and Precautions (5.1 , 5.4) ]. Monitor cardiopulmonary and renal functions throughout the treatment course. [see Warnings and Precautions (5.1 , 5.5 , 5.6 , 5.7) ]. Administer in an inpatient hospital setting. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available [see Dosage and Administration (2.1) , and Adverse Reactions (6.1) ] . WARNING: TREATMENT-RELATED MORTALITY, PROLONGED SEVERE CYTOPENIA, SEVERE INFECTION, CARDIOPULMONARY and RENAL IMPAIRMENT See full prescribing information for complete boxed warning. Monitor patients for prolonged severe cytopenia and monitor for internal organ hemorrhage ( 5.1 , 5.2 , 5.3 ) Treat severe infections ( 5.1 , 5.4 ) Monitor cardiopulmonary and renal functions throughout the treatment course ( 5.1 , 5.5 , 5.6 , 5.7 ) Administer in an inpatient hospital…

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 263 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 3 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Electrolyte Disturbancecorroborated · ROR 4.3 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

Thrombotic Microangiopathy

ROR 10.3795% CI 2.58–41.70· 2 reports

SIADH / Hyponatremia

ROR 8.1495% CI 4.03–16.45· 8 reports

Electrolyte Disturbance

ROR 4.3095% CI 2.29–8.09· 10 reports

FAERS outcomes & reporting trend· 20.2% of reports w/ death · 52.1% w/ hospitalization

20.2%

Reported with a death outcome

53 of 263 reports

52.1%

Reported with hospitalization

137 of 263 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 263 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 12.4895% CI 8.06–19.31· 22 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury22

General / constitutional

Pyrexia40Chills22Malaise14Multiple Organ Dysfunction Syndrome12Fatigue11

Blood & lymphatic

Pancytopenia18Febrile Neutropenia16Thrombocytopenia16Anaemia12Cytopenia10

Respiratory

Hypoxia21Pleural Effusion14Dyspnoea13Acute Respiratory Failure11Respiratory Failure11

Gastrointestinal

Nausea16Diarrhoea13Vomiting11

Vascular

Hypotension29

Cardiac

Atrial Fibrillation14Tachycardia13

Psychiatric

Mental Status Changes12Confusional State11

Immune / infection

Cytokine Release Syndrome17

Skin

Rash15

Guidelines & consensus· 13

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Lifileucel sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Arsenic trioxide

Trisenox · Differentiating agent

Profile

Differentiation syndrome; QT prolongation.

PREATNLYTE

Moderate#1 · 85% phenotype match

Enasidenib

Idhifa · IDH2 inhibitor

Profile

Differentiation syndrome and tumor lysis.

PREATNLYTE

Moderate#2 · 85% phenotype match

Ivosidenib

Tibsovo · IDH1 inhibitor

Profile

Differentiation syndrome → AKI; tumor lysis.

PRELYTEATN

Moderate#3 · 85% phenotype match

Afamitresgene autoleucel (Afami-cel)

Tecelra · MAGE-A4 TCR-T cell therapy

Profile

First TCR-T cell therapy for a solid tumor; CRS-associated hemodynamic AKI.

PRELYTE

Moderate#4 · 84% phenotype match

Ziftomenib

Komzifti · Menin inhibitor

Profile

2025 NPM1-mutated AML menin inhibitor; differentiation syndrome and tumor lysis.

PRELYTE

Moderate#5 · 84% phenotype match

Mobocertinib

Exkivity · EGFR exon20 TKI

Profile

Diarrhea-driven prerenal AKI; QT prolongation.

PREATNLYTE

Mild#6 · 83% phenotype match

Compare Lifileucel with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Other targeted agents

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.