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c-Met ADC (MMAE)

Telisotuzumab vedotin (Teliso-V)

Emrelis · c-Met ADC (MMAE)

c-Met ADC (MMAE) · approved 2025 · 3 references

c-Met-directed MMAE antibody-drug conjugate; renal risk is class-extrapolated from MMAE payload handling.

Signature injury
Acute Tubular Necrosis
Severity
Moderate
Reversibility
Variable
Onset
Onset is not well characterized for this agent; with cytotoxic ADC payloads, tubular injury would typically evolve over days to a few weeks of cumulative exposure.

Signature kidney injury & incidence

Acute Tubular Necrosis.

Drug-specific renal toxicity data for telisotuzumab vedotin are sparse. In the pivotal LUMINOSITY trial the dominant toxicities were peripheral neuropathy, peripheral edema, hypoalbuminemia, fatigue, and nausea; clinically significant nephrotoxicity was not highlighted as a frequent or signature event. Any renal risk is therefore largely class-extrapolated from MMAE-bearing ADCs rather than measured for this agent. A precise renal incidence rate cannot be stated from existing literature.

Source: 38843488

Reported injury signatures: Acute Tubular Necrosis, Electrolyte Disturbance.

Renal toxicity profile

  1. Acute Tubular NecrosisPrimary
  2. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Subacute (~1–6 weeks) — Onset is uncharacterized, but cytotoxic ADC payload tubular injury would typically evolve over days to a few weeks of cumulative exposure.

Mechanism of kidney injury

Injury is inferred from the MMAE payload. After partial deconjugation or nonspecific uptake, free or antibody-bound MMAE can be handled by the proximal tubule, where the antimitotic payload may injure highly metabolically active tubular epithelium and produce acute tubular injury (ATN). Marked hypoalbuminemia and peripheral edema seen with the drug can also shift intravascular volume and contribute indirectly to prerenal physiology. These pathways are extrapolated from the ADC/MMAE class; agent-specific renal histopathology is not established.

Clinical presentation

When it occurs, presentation is expected to resemble nontoxic ATN: a rise in serum creatinine with bland urine sediment, possibly with low-grade proteinuria and electrolyte disturbances. Hypoalbuminemia and peripheral edema are commonly observed with the drug and may accompany or confound the renal picture.

Management

Management is supportive and follows general drug-induced ATN principles: discontinue or hold the offending agent, restore volume, remove concurrent nephrotoxins, and provide supportive care while renal function recovers. No agent-specific antidote exists. Treat associated hypoalbuminemia/edema and electrolyte abnormalities as clinically indicated.

Risk factors

  • Pre-existing chronic kidney disease
  • Volume depletion or hypoalbuminemia
  • Concomitant nephrotoxins (contrast, aminoglycosides, NSAIDs)
  • Older age and reduced baseline renal reserve

Prevention

  • Maintain euvolemia and correct hypoalbuminemia where possible
  • Hold or dose-modify per label for significant toxicity

Renal dose adjustment

No dedicated renal dose adjustment is established. The drug has not been formally studied in severe renal impairment or dialysis; mild-to-moderate impairment is not expected to require adjustment based on the antibody-conjugated pharmacology, but data are limited. Follow the current FDA label for dose modifications driven by toxicity.

Dialyzability & ESKD dosing

Not established. As a large antibody-drug conjugate, telisotuzumab vedotin is not expected to be appreciably dialyzable; the small-molecule MMAE payload is highly protein- and tissue-bound, so removal by hemodialysis is unlikely to be clinically meaningful.

Differential diagnosis

In a patient on Teliso-V with rising creatinine, distinguish class-extrapolated tubular injury (ATN) from prerenal azotemia driven by hypoalbuminemia, edema, and poor intake, and from concurrent nephrotoxins or contrast. Bland sediment favors ATN or prerenal physiology over glomerular or interstitial disease.

Monitoring

  • Serum albumin
  • Urinalysis for proteinuria/sediment if AKI develops
  • Volume status and peripheral edema

Key trials & series

  • LUMINOSITY (NCT03539536): Phase II of telisotuzumab vedotin monotherapy in previously treated c-Met-overexpressing EGFR wild-type nonsquamous NSCLC; supported accelerated approval. Predominant toxicities were peripheral neuropathy, edema, and hypoalbuminemia rather than a defined nephrotoxicity signal.

Clinical pearls

  • The proximal tubule is the plausible target if liberated MMAE causes injury, consistent with the proximal/ATN signature assigned here.
  • No renal dose adjustment is established; manage supportively and avoid stacking additional nephrotoxins.

Anticancer mechanism

Telisotuzumab vedotin is an antibody-drug conjugate (ADC) in which an antibody against c-mesenchymal-epithelial transition factor (c-Met) is linked to the microtubule inhibitor monomethyl auristatin E (MMAE). After binding c-Met on tumor cells, the conjugate is internalized and the cleavable linker liberates MMAE, which disrupts the microtubule network and triggers cell-cycle arrest and apoptosis. It received accelerated FDA approval in May 2025 for c-Met-high, EGFR wild-type nonsquamous NSCLC after prior systemic therapy.

Guidelines & consensus

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.

  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525

References

3 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.Camidge DR, Bar J, Horinouchi H, et al. · J Clin Oncol · 2024 · PMID 38843488
  2. 2.Telisotuzumab Vedotin: First Approval.Blair HA. · Drugs · 2025 · PMID 40736649
  3. 3.Antibody-drug conjugates in lung and breast cancer: current evidence and future directions-a position statement from the ETOP IBCSG Partners Foundation.Peters S, Loi S, Andre F, et al. · Ann Oncol · 2024 · PMID 38648979
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.