EZH2 inhibitor
Tazemetostat
Tazverik · TAZ
EZH2 inhibitor · approved 2020 · 7 references
First-in-class EZH2 inhibitor with a generally low direct renal toxicity — the kidney-relevant concern is treatment-related tumor lysis in lymphoma.
- Signature injury
- Prerenal / Hemodynamic AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Tumor lysis, if it occurs, is early after response; prerenal effects track intercurrent GI toxicity.
Signature kidney injury & incidence
Prerenal / Hemodynamic AKI — representative grade ≥3 incidence ~7%.
Tazemetostat is generally well tolerated with low direct organ toxicity; the noted boxed risk is secondary T-cell lymphoma/myeloid malignancy. Tumor lysis is an uncommon, treatment-related concern in responding lymphoma. A discrete AKI rate is not quantified and direct nephrotoxicity is low. Reported rate: grade >=3 hyponatremia in 7% — 74 patients with relapsed or refractory malignant pleural mesothelioma (99% BAP1-inactivated) receiving single-agent… (Zauderer 2022, PMID 35588752).
Source: Zauderer et al., Lancet Oncol 2022
Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance.
Renal toxicity profile
- Prerenal / Hemodynamic AKIPrimary
- Electrolyte DisturbanceSecondary
Onset timing & rechallenge
Acute (~1–7 days) — Tumor lysis, if it occurs, is early after response; prerenal effects track GI toxicity.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- High tumor burden/bulky lymphoma (tumor-lysis risk)
- Pre-existing CKD and concurrent nephrotoxins
- Volume depletion from GI toxicity
- Hyperuricemia at baseline
Prevention
- Tumor-lysis risk assessment with hydration +/- allopurinol or rasburicase in higher-risk lymphoma
- Maintain hydration; manage GI toxicity
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Serum creatinine, uric acid, phosphate and potassium early in responders (TLS surveillance)
- CBC per schedule (and surveillance for secondary malignancy)
- Volume status with GI toxicity
Key trials & series
- Morschhauser et al. (Lancet Oncol 2020) — registrational follicular lymphoma cohort
- Gounder et al. (Lancet Oncol 2020) — epithelioid sarcoma cohort
Clinical pearls
- Tazemetostat is generally well tolerated; the kidney-relevant concern is tumor lysis in responding lymphoma, not the drug itself.
- Risk-stratify bulky lymphoma for TLS and pre-treat with hydration +/- rasburicase.
- Remember the boxed secondary-malignancy risk when counseling and on long-term follow-up.
- No tazemetostat-specific renal lesion is described.
Anticancer mechanism
Note
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
7 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 studyZauderer MG et al. · The Lancet. Oncology · 2022 · PMID 35588752
- 2.Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.Morschhauser F et al. · Lancet Oncol · 2020 · PMID 33035457
- 3.Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study.Gounder M et al. · Lancet Oncol · 2020 · PMID 33035459
- 4.Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.Italiano A et al. · Lancet Oncol · 2018 · PMID 29650362
- 5.EZH2 inhibition by tazemetostat: mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma.Julia E et al. · Future Oncol · 2021 · PMID 33709777
- 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
- 7.Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress.Matuszkiewicz-Rowinska J et al. · Kidney Blood Press Res · 2020 · PMID 32998135