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Anti-CCR4 antibody

Mogamulizumab

Poteligeo · MOG

Anti-CCR4 antibody · approved 2018 · 6 references

Defucosylated anti-CCR4 antibody for cutaneous T-cell lymphoma — renal-relevant risks are treatment-related tumor lysis and rare AKI, not a direct nephropathy.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Mild
Reversibility
Reversible
Onset
Infusion reactions early; rash over weeks; tumor lysis early in responders.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI — representative incidence ~2.5%.

Drug rash and infusion reactions are characteristic; tumor lysis occurred in roughly 2-3% in some series. AKI is rare and largely secondary to tumor lysis or volume shifts; a discrete AKI incidence is not well quantified. Reported rate: tumor lysis syndrome in 2.5% — 484 patients (safety analysis population) with CCR4-positive relapsed or refractory adult T-cell leukemia-lymphoma in a… (Ishitsuka 2017, PMID 28597329).

Source: Kim et al., Lancet Oncol 2018 (MAVORIC); Ishitsuka et al., Int J Hematol 2017

Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance.

Renal toxicity profile

  1. Prerenal / Hemodynamic AKIPrimary
  2. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Acute (~1–7 days) — Tumor lysis early in responders.

Mechanism of kidney injury

Mogamulizumab has no characteristic direct renal lesion. Its renal relevance is indirect: (1) in patients with circulating tumor burden (Sezary syndrome), rapid CCR4-positive cell killing can cause tumor lysis with urate/phosphate intratubular crystal nephropathy and ATN; (2) infusion reactions and the characteristic skin toxicity with systemic inflammation can produce transient hemodynamic effects. Depletion of regulatory T cells underlies the autoimmune-flavored skin and immune adverse events but is not a defined renal mechanism.

Clinical presentation

Drug eruption/rash, infusion reactions; in responders with high tumor burden, TLS labs (hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia) and AKI early in treatment. Otherwise renal function is usually preserved.

Management

Treat tumor lysis with aggressive hydration, urate-lowering therapy and electrolyte correction (dialysis if refractory). Manage infusion reactions and drug rash (topical/systemic steroids; hold for severe rash). Restore volume for transient prerenal AKI; renal effects are generally reversible.

Risk factors

  • High circulating tumor burden / Sezary syndrome (tumor-lysis risk)
  • Pre-existing CKD and concurrent nephrotoxins
  • Volume depletion
  • Inadequate infusion premedication

Prevention

  • Tumor-lysis risk assessment with hydration +/- allopurinol or rasburicase in high-burden disease
  • Infusion premedication; monitor for and manage drug rash

Renal dose adjustment

No dose adjustment for renal impairment (a monoclonal antibody, not renally cleared); interruptions are driven by rash and infusion reactions.

Dialyzability & ESKD dosing

A monoclonal antibody; not dialyzable. Dialysis is used for TLS metabolic complications, not drug removal.

Differential diagnosis

Distinguish tumor-lysis crystalline nephropathy (early, in high-burden responders) from prerenal azotemia and other AKI causes. The drug rash is immune-mediated but not a renal lesion.

Monitoring

  • TLS labs in higher-burden responders (uric acid, phosphate, potassium, creatinine)
  • Skin assessment for drug rash
  • Vital signs during infusions

Key trials & series

  • MAVORIC (Kim, Lancet Oncol 2018) — registrational RCT vs vorinostat in CTCL
  • Ishitsuka et al. (Int J Hematol 2017) — tumor-lysis observations (~2-3%)

Clinical pearls

  • The kidney-relevant risk is tumor lysis in high-burden (Sezary) disease, not a direct mogamulizumab nephropathy.
  • Characteristic drug rash reflects regulatory T-cell depletion — manage with steroids, not as renal disease.
  • As an antibody it needs no renal dose adjustment and is not dialyzable.
  • Risk-stratify circulating tumor burden for TLS before the first infusions.

Anticancer mechanism

Defucosylated humanized monoclonal antibody against CC chemokine receptor 4 (CCR4), expressed on malignant T cells and regulatory T cells. Glycoengineering markedly enhances antibody-dependent cellular cytotoxicity, depleting CCR4-positive cells in mycosis fungoides and Sezary syndrome.

Note

The renal link is indirect — chiefly treatment-related tumor lysis in high-burden disease and rare transient AKI rather than a direct lesion.

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

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

  1. 1.Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.Kim YH et al. · Lancet Oncol · 2018 · PMID 30100375
  2. 2.Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma.Duvic M et al. · Blood · 2015 · PMID 25605368
  3. 3.Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance.Ishitsuka K et al. · Int J Hematol · 2017 · PMID 28597329
  4. 4.Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sézary Syndrome.Hirotsu KE et al. · JAMA Dermatol · 2021 · PMID 33881447
  5. 5.Mogamulizumab-induced Mucocutaneous Lichenoid Reaction: A Case Report and Short Review.Trager MH et al. · Acta Derm Venereol · 2020 · PMID 32449779
  6. 6.Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus.Cairo MS et al. · Br J Haematol · 2010 · PMID 20331465
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.