Odronextamab

Crystal / Obstructive Nephropathy — representative incidence ~19%.

There is no clean, drug-specific published incidence of odronextamab acute kidney injury as a discrete endpoint; the renal risk is inferred from its cytokine-release and tumor-lysis complications, which the ELM trials do quantify. In the phase 1 ELM-1 trial (Bannerji, Lancet Haematol 2022; n=145 heavily pretreated relapsed/refractory B-NHL), grade >=3 hypophosphatemia occurred in 27/145 (19%), cytokine release syndrome was the single most common serious adverse event (41/145, 28%), and one of four treatment-related deaths was due to tumor-lysis syndrome. With the optimized 0.7/4/20 mg step-up in the phase 2 ELM-2 cohorts, any-grade CRS was 53.3% (grade >=3 1.7%) in DLBCL (Kim WS, Nat Cancer 2025) and 56% (grade >=3 1.7%) in follicular lymphoma (Kim TM, Ann Oncol 2024) — CRS remained the dominant treatment-emergent adverse event even after mitigation. Kidney injury in this setting rides on these events (CRS hemodynamics, TLS crystal nephropathy, sepsis) rather than on any intrinsic tubular toxicity, so exact AKI rates are not well established and should not be overstated.

Source: Bannerji ELM-1, Lancet Haematol 2022 (grade >=3 hypophosphatemia 19%; CRS 28% serious; one fatal TLS)

Reported injury signatures: Crystal / Obstructive Nephropathy, Prerenal / Hemodynamic AKI, Electrolyte Disturbance, Acute Tubular Necrosis.

1. Crystal / Obstructive NephropathyPrimary
2. Prerenal / Hemodynamic AKISecondary
3. Electrolyte DisturbanceSecondary
4. Acute Tubular NecrosisSecondary

Acute (~1–7 days) — CRS begins within hours to 1-2 days and TLS within ~12-72 hours of effective cytoreduction, so kidney injury concentrates in the first days to first couple of weeks, around cycle 1.

• High tumor burden / bulky disease or high circulating lymphoma-cell mass (greater lysis and cytokine load)
• High baseline LDH, uric acid, or phosphate (TLS-prone biochemistry)
• The cycle-1 step-up and first full target dose (peak CRS/TLS window)
• Pre-existing chronic kidney disease or volume depletion
• Concurrent nephrotoxins or infection/sepsis in a heavily pretreated host
• Severe or higher-grade CRS
• Inadequate hydration or omission of TLS prophylaxis

• Risk-stratify for TLS before dosing (tumor bulk, LDH, uric acid, phosphate, renal function) and give prophylaxis accordingly
• Vigorous IV hydration around step-up and the first full dose to maintain urine output and dilute tubular urate/phosphate
• Allopurinol for standard TLS risk; rasburicase for high risk or established hyperuricemia (avoid in G6PD deficiency)
• Use the mandated cycle-1 step-up dosing schedule to limit the magnitude of the first cytokine/lysis wave
• Premedication (corticosteroid, antihistamine, antipyretic) and monitored administration to catch CRS early
• Frequent TLS labs and vital-sign monitoring during the high-risk window; correct volume depletion and hold nephrotoxins where possible

• TLS panel (uric acid, phosphate, potassium, calcium, LDH, creatinine) at baseline and frequently during step-up and the first full dose
• Continuous/close vital-sign monitoring for CRS (fever, hypotension, hypoxia) during and after dosing
• Urine output and volume status during the high-risk cycle-1 window
• Serum phosphate and magnesium (hypophosphatemia is common; TLS drives hyperphosphatemia/hypocalcemia)
• Serial creatinine/eGFR to detect and grade AKI
• Infection surveillance given the high infection rate in this population (a competing/additive AKI driver)

• ELM-1 (Bannerji, Lancet Haematol 2022) — first-in-human phase 1 dose-escalation/expansion in relapsed/refractory CD20+ B-NHL (n=145); CRS was the most common serious adverse event (28%), grade >=3 hypophosphatemia occurred in 19%, and one of four treatment-related deaths was tumor-lysis syndrome — the trial that anchors the CRS/TLS renal-risk signature.
• ELM-2 DLBCL (Kim WS, Nat Cancer 2025) — phase 2 relapsed/refractory diffuse large B-cell lymphoma cohort; with the 0.7/4/20 mg step-up, CRS was the most common treatment-emergent event (53.3%, grade >=3 1.7%) and infections were frequent (64.6%), framing the on-target immune-activation toxicity that underlies AKI.
• ELM-2 follicular lymphoma (Kim TM, Ann Oncol 2024) — phase 2 relapsed/refractory follicular lymphoma cohort (ORR 80%); CRS 56% (grade >=3 1.7% with step-up dosing), the registrational efficacy/safety basis in FL.

• The kidney is a bystander to on-target immunology: odronextamab does not poison tubules — it lyses B cells fast, and TLS crystal nephropathy plus CRS hemodynamics do the renal damage.
• TLS is the signature renal event and it is front-loaded — risk peaks at the cycle-1 step-up and first full dose, which is exactly why the step-up schedule and TLS prophylaxis exist.
• Treat the driver, not just the creatinine: for CRS-associated AKI, tocilizumab with or without steroids plus fluids reverses the prerenal insult; for TLS, hydration and rasburicase are the levers.
• Hypophosphatemia is a common isolated lab finding (grade >=3 in 19% in ELM-1), but in the lysis window watch instead for the TLS pattern of hyperphosphatemia, hyperkalemia, hyperuricemia, and hypocalcemia.
• Dialysis does not remove this ~150 kDa antibody, but renal replacement therapy is still the right tool for refractory TLS metabolites or oliguric AKI — clear the consequences, not the drug.
• AKI here is usually reversible with prompt supportive care, but it is not benign: ELM-1 recorded a fatal tumor-lysis event, so high tumor burden warrants aggressive prophylaxis and monitoring.

• TLS Expert Panel (2008) — Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based reviewPrevention is the best management: hydration plus prophylactic rasburicase for high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk, and monitoring for low-risk; for established TLS add aggressive hydration and diuresis plus allopurinol or rasburicase for hyperuricemia. Urinary alkalinization is NOT recommended.J Clin Oncol · PMID 18509186
• TLS Consensus Panel (2010) — Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensusStratify each patient as low/intermediate/high TLS risk using tumor type, bulk/stage, proliferation rate, baseline laboratory TLS, and renal impairment/involvement, then match prophylaxis intensity (monitoring vs allopurinol vs rasburicase) to the assigned risk level.Br J Haematol · PMID 20331465
• BCSH (2015) — Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in HaematologyRisk-adapted prophylaxis and management of TLS in haematological malignancy: hydration with allopurinol for lower-risk and rasburicase for high-risk patients, with monitoring of electrolytes and renal function to prevent and treat AKI.Br J Haematol · PMID 25876990
• Cairo-Bishop (2004) — Tumour lysis syndrome: new therapeutic strategies and classificationDefines the Cairo-Bishop criteria distinguishing laboratory TLS (>=2 metabolic abnormalities: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia within 3 days before to 7 days after therapy) from clinical TLS (laboratory TLS plus AKI, cardiac arrhythmia, or seizure), with a severity grading scheme adopted by subsequent guidelines.Br J Haematol · PMID 15384972
• ASTCT (2019) — ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector CellsGrade CRS by fever, hypotension and hypoxia (grades 1-4) and grade ICANS using the ICE/encephalopathy score plus level of consciousness, seizures, motor findings and raised intracranial pressure/edema; this is the standard severity framework that triggers tocilizumab and corticosteroid escalation in CAR-T and bispecific antibody toxicity (the Lee 2019 consensus).Biol Blood Marrow Transplant · PMID 30592986
• 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 (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