Telisotuzumab vedotin (Teliso-V)
Emrelis · c-Met ADC (MMAE)
c-Met MMAE antibody-drug conjugate; proximal tubular ATN risk extrapolated from the ADC/MMAE class.
ATNLYTE
Moderate#1 · 89% phenotype match
Melphalan flufenamide (melflufen)
Pepaxto · Melflu
Peptide-conjugated alkylator · approved 2021 · 4 citations
Up to date· through 2026
Thinly sourced3/9 · 3 signals
- Not met: 4 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 5y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- Met: Landmark reference
- Met: Current through 2026
- Not 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 peptide-conjugated alkylator that floods myeloma cells with melphalan — and its exposure rises as the kidney fails.
ModeratePeptide-conjugated alkylating agent
Relapsed/refractory multiple myeloma (with dexamethasone)
§01
Signature kidney injury
Signature lesion
Direct nephrotoxicity is not a prominent trial signal; the renal relevance is pharmacokinetic and disease-context. A dedicated phase II study (BRIDGE) in myeloma patients with moderate or severe renal impairment characterized melphalan exposure across renal function and supported a reduced 30 mg dose for moderate impairment, with no new safety signals but substantial treatment-emergent toxicity (including deaths in a heavily pretreated population). As a melphalan-delivery system, its renal liabilities mirror the alkylator class (myelosuppression, and the alkylator-associated risk of tubular injury at high exposure).Source: Pour et al., Clin Lymphoma Myeloma Leuk 2026 (BRIDGE renal-impairment phase II)
Onset & rechallenge
Time to injurySubacute (~1–6 weeks)
Renal change, when it occurs, is typically subacute and multifactorial.
Distilled from: “Cytopenias within the first cycles; any renal change is typically subacute and multifactorial.”
§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.
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
§03
Kidney injury
Mechanism of kidney injury
Melflufen is a delivery vehicle that liberates melphalan intracellularly. The kidney is principally the elimination/exposure determinant: in renal impairment, altered handling of the released alkylator changes exposure (the BRIDGE study guided a moderate-impairment dose reduction), and accumulation amplifies systemic alkylator toxicity — chiefly profound myelosuppression. By alkylator-class analogy, high melphalan exposure can stress the proximal tubule and, with tumor cytoreduction, contribute to electrolyte disturbances; intrinsic, biopsy-defined melflufen tubular injury is not well characterized. The dominant, mechanism-anchored renal concern is exposure-driven toxicity in reduced GFR requiring dose adjustment.
Clinical presentation
Predominantly hematologic toxicity (thrombocytopenia, neutropenia, anemia). A creatinine rise would most often reflect underlying myeloma kidney disease, volume depletion, or tumor-lysis-related electrolyte shifts rather than a discrete melflufen tubular lesion. Watch for cytopenia-related complications.
Management
Dose-reduce for renal impairment, interrupt/modify for hematologic toxicity, and provide supportive care (transfusion, growth factors). Manage myeloma-related renal disease and electrolytes; nephrology input for unexplained AKI.Lesion-level management framework
Risk factors
- Moderate-to-severe renal impairment (altered melphalan exposure)
- Underlying myeloma cast nephropathy / hypercalcemia
- Heavy prior therapy and low marrow reserve
- Volume depletion
Prevention
- Assess renal function and reduce the dose for moderate impairment per BRIDGE/label guidance
- Treat underlying myeloma renal disease and maintain hydration
- Tumor-lysis precautions in high-burden disease
Anticancer mechanism· how it treats cancer
Lipophilic peptide-drug conjugate of melphalan. It diffuses readily into cells and is rapidly cleaved by aminopeptidases (markedly overexpressed in myeloma cells), releasing and trapping high intracellular concentrations of the alkylator melphalan — yielding roughly a 50-fold enrichment of payload versus free melphalan. With dexamethasone for relapsed/refractory multiple myeloma (regulatory status has shifted; included for onconephrology completeness).
Note · Profile included for onconephrology completeness; melflufen's U.S. regulatory status has changed since 2021. The renal message is exposure-and-dose (BRIDGE supports a reduced dose in moderate impairment), not a well-defined intrinsic tubular lesion. Distinct from parent melphalan as a peptide-conjugate with its own PK.
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Clinical depth
Renal dose adjustment
Reduced dose (30 mg) recommended for moderate renal impairment (eGFR ~30 to <45 mL/min/1.73 m2) based on the BRIDGE PK study; data in severe impairment are limited (a 20 mg dose was studied). Recalculate eGFR before dosing.
Dialyzability & ESKD dosing
Released melphalan is a small molecule with limited published dialyzability data for the conjugate; no established dosing in dialysis-dependent patients. Use with caution and close monitoring in advanced CKD.
Differential diagnosis
A creatinine rise on melflufen is usually myeloma cast nephropathy, hypercalcemia, prerenal volume depletion, or tumor lysis rather than a primary drug lesion; alkylator-class tubular injury is a theoretical high-exposure concern. Free light chains and calcium help separate disease relapse from drug effect.
Monitoring
- Complete blood count before each cycle and at nadir
- eGFR before dosing
- Serum calcium, free light chains (disease activity)
- Uric acid, phosphate, potassium and creatinine in high-burden disease
Key trials & series
- OCEAN / HORIZON melflufen myeloma program (efficacy/safety context)
- BRIDGE (Pour Clin Lymphoma Myeloma Leuk 2026) renal-impairment phase II PK/dosing study
Clinical pearls
- Melflufen is a melphalan delivery system — think alkylator toxicity, dominated by myelosuppression, with renal function setting exposure.
- Most renal events trace to the myeloma (cast nephropathy, hypercalcemia) rather than to melflufen itself.
Where it strikes· nephron segments & injury signatures
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Beyond the kidney — non-renal toxicities· 3 organ systems
Class-level context for the major non-renal toxicities of the Peptide-conjugated alkylator class.
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression; secondary malignancy risk
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Ifosfamide encephalopathy (chloroacetaldehyde)
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- High-dose cyclophosphamide cardiotoxicity
§05
References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 2021–2026 · 2 since 2024Primary (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.
- 1.Pharmacokinetics and Metabolism of Melflufen, an Alkylating Peptide-Drug Conjugate, in Patients with Relapsed Refractory Multiple Myeloma.Huledal G, Ruiz-Garcia A, Kawakatsu S, et al · J Clin Pharmacol · 2024 · PMID 37752623PK/metabolism study showing melflufen is intracellularly converted to melphalan and that clearance increases with eGFR, supporting that renal function is an exposure/elimination determinant for the liberated alkylator.
- 2.LandmarkBRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function.Pour L et al. · Clin Lymphoma Myeloma Leuk · 2026 · PMID 42215355Dedicated renal-impairment PK study guiding a reduced 30 mg dose in moderate impairment, with safety in moderate-to-severe impairment.
- 3.Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma.Morabito F et al. · Drug Des Devel Ther · 2021 · PMID 34262262Reviews the aminopeptidase-driven mechanism and ~50-fold intracellular melphalan enrichment that defines melflufen's pharmacology.
- 4.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107Onconephrology reference for alkylator nephrotoxicity and renal dose-modification principles.
Guidelines & consensus· 14
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 Melphalan flufenamide (melflufen) 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Trabectedin
Yondelis · Marine alkylating agent
Rhabdomyolysis → pigment nephropathy; hepatotoxicity.
ATNLYTE
Moderate#2 · 88% phenotype match
Nedaplatin
Aqupla · Platinum agent
Second-gen platinum with reduced renal toxicity vs cisplatin.
ATNLYTE
Moderate#3 · 86% phenotype match
Streptozocin
Zanosar · Nitrosourea alkylator
Classic proximal tubular toxin → Fanconi and dose-limiting AKI.
FANCATNLYTE
Severe#4 · 76% phenotype match
Plicamycin (mithramycin)
Mithracin · Antitumor antibiotic
Cumulative tubular ATN; hypocalcemia is an on-target antiresorptive effect.
ATNLYTE
Moderate#5 · 75% phenotype match
Gallium nitrate
Ganite · Antineoplastic metal salt
Dose-limiting acute tubular necrosis; potentiated by dehydration and concurrent nephrotoxins.
ATNPRELYTE
Moderate#6 · 70% phenotype match
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 Alkylating 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.
- 1Altretamine (hexamethylmelamine)PRE — Prerenal / Hemodynamic AKIMild
- 2DacarbazinePRE — Prerenal / Hemodynamic AKIMild
- 3EstramustinePRE — Prerenal / Hemodynamic AKIMild
- 4ChlorambucilSIADH — SIADH / HyponatremiaMild
- 5ThiotepaCYST — Hemorrhagic CystitisFAERS AKIMild
- 6CyclophosphamideSIADH — SIADH / HyponatremiaFAERS AKIMild
- 7MelphalanSIADH — SIADH / HyponatremiaFAERS AKIMild
- 8TemozolomideSIADH — SIADH / HyponatremiaFAERS AKIMild
- 9LurbinectedinATN — Acute Tubular NecrosisFAERS AKIMild
- 10Lomustine (CCNU)CIN — Chronic Interstitial NephropathyModerate
- 11MechlorethamineLYTE — Electrolyte DisturbanceModerate
- 12Melphalan flufenamide (melflufen)· this agentATN — Acute Tubular NecrosisModerate
- 13ProcarbazineATN — Acute Tubular NecrosisModerate
- 14FotemustineCIN — Chronic Interstitial NephropathyModerate
- 15Nimustine (ACNU)CIN — Chronic Interstitial NephropathyModerate
- 16BusulfanTMA — Thrombotic MicroangiopathyFAERS AKIModerate
- 17Carmustine (BCNU)CIN — Chronic Interstitial NephropathyFAERS AKIModerate
- 18TrabectedinATN — Acute Tubular NecrosisFAERS AKIModerate
- 19BendamustineXTAL — Crystal / Obstructive NephropathyFAERS AKIModerate
- 20StreptozocinFANC — Fanconi SyndromeSevere
- 21IfosfamideFANC — Fanconi SyndromeFAERS AKISevere
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.