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Antibody-drug conjugate (FRα/DM4)

Mirvetuximab soravtansine

Elahere · MIRV

Antibody-drug conjugate (FRα/DM4) · approved 2022 · 4 references

An FRα/DM4 conjugate for ovarian cancer — ocular and GI toxicity dominate; renal data are emerging.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Mild
Reversibility
Variable
Onset
Variable; tracks with GI toxicity during treatment cycles.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI.

Direct nephrotoxicity is not a prominent trial signal; ocular (keratopathy/blurred vision, ~50% any-grade across pooled trials) and GI/fatigue toxicities dominate. AKI is case-level and chiefly volume-mediated (GI toxicity). Renal-specific incidence is not quantified.

Source: Moore et al., N Engl J Med 2023 (MIRASOL)

Reported injury signatures: Prerenal / Hemodynamic AKI.

Onset timing & rechallenge

Variable / unpredictable — Prerenal injury is variable and tracks with GI toxicity during treatment cycles.

Mechanism of kidney injury

Indirect/hemodynamic: nausea, vomiting and diarrhea cause volume depletion and prerenal AKI. A direct tubular mechanism is not established in humans; FRα is expressed in proximal tubule (the basis for folate-receptor tracer uptake by the kidney), but clinically meaningful tubular toxicity has not emerged at approved doses. The maytansinoid payload concentrates instead in corneal epithelium, producing the hallmark ocular toxicity.

Clinical presentation

AKI in the setting of GI toxicity/dehydration with bland sediment; renal function otherwise usually preserved. Ocular symptoms (blurred vision, keratopathy, dry eye) are the hallmark toxicity and are generally low-grade and reversible.

Management

Rehydrate, manage GI toxicity, hold drug for significant AKI, supportive care; ocular toxicity is managed by ophthalmology-guided dose modification.

Risk factors

  • GI toxicity and dehydration
  • Pre-existing CKD
  • Concurrent nephrotoxins

Prevention

  • Manage nausea/diarrhea and maintain hydration
  • Prophylactic ocular surface care (lubricating and corticosteroid eye drops)

Renal dose adjustment

No renal dose adjustment defined for mild-moderate impairment; data are limited in severe impairment/ESKD. DM4 is hepatically metabolized rather than renally cleared.

Dialyzability & ESKD dosing

Not appreciably dialyzed (large ADC; protein-bound maytansinoid payload).

Differential diagnosis

AKI is prerenal from GI losses (volume-responsive, bland sediment) rather than tubular; the management-defining toxicity is ocular, paralleling belantamab mafodotin. Nephron injury would be unexpected and should prompt a search for alternative causes.

Monitoring

  • Ophthalmologic exam at baseline, every other cycle for the first 8 cycles, and as indicated

Key trials & series

  • MIRASOL (Moore NEJM 2023, phase III)
  • SORAYA (Matulonis JCO 2023, registrational)
  • Hendershot Gynecol Oncol Rep 2023 (pooled ocular safety, n=464)

Clinical pearls

  • Mirvetuximab and belantamab share the ADC ocular signature - eye care and exams, not renal monitoring, define routine surveillance.
  • FRα is expressed in the proximal tubule (hence renal tracer uptake), yet clinical tubular toxicity has not materialized - the kidney risk is hemodynamic.
  • Most AKI is dehydration from GI toxicity and reverses with fluids.

Anticancer mechanism

Antibody-drug conjugate targeting folate receptor alpha (FRα) and delivering the maytansinoid microtubule inhibitor DM4 via a cleavable disulfide linker. Approved for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.

Note

Renal data are emerging; the defining toxicities are ocular and GI rather than renal.

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

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

  1. 1.Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.Moore KN et al. · N Engl J Med · 2023 · PMID 38055253
  2. 2.Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study.Matulonis UA et al. · J Clin Oncol · 2023 · PMID 36716407
  3. 3.Strategies for prevention and management of ocular events occurring with mirvetuximab soravtansine.Hendershot A et al. · Gynecol Oncol Rep · 2023 · PMID 37102083
  4. 4.Antibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know.Markides DM et al. · Ann Emerg Med · 2024 · PMID 39641680
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.