Bispecific (BCMA×CD3)
Elranatamab
Elrexfio · ELRA
Bispecific (BCMA×CD3) · approved 2023 · 7 references
A BCMAxCD3 bispecific for myeloma whose emerging renal risk stems from cytokine release and, occasionally, tumor lysis.
- Signature injury
- Prerenal / Hemodynamic AKI
- Severity
- Moderate
- Reversibility
- Reversible
- Onset
- Early, concentrated around the two-step priming doses and the first full doses.
Signature kidney injury & incidence
Prerenal / Hemodynamic AKI.
Cytokine release syndrome is common with elranatamab (about 58% in the pivotal MagnetisMM-3 trial, largely grade 1-2 with the two-step priming regimen); CRS-associated acute kidney injury, and occasionally tumor-lysis-related injury, are emerging case-level signals that are not separately well quantified, superimposed on frequent myeloma kidney disease.
Source: Lesokhin et al., Nat Med 2023
Reported injury signatures: Prerenal / Hemodynamic AKI, Acute Tubular Necrosis, Crystal / Obstructive Nephropathy.
Renal toxicity profile
- Prerenal / Hemodynamic AKIPrimary
- Acute Tubular NecrosisSecondary
- Crystal / Obstructive NephropathySecondary
Onset timing & rechallenge
Acute (~1–7 days) — Early — around the two-step priming doses and the first full doses.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Higher-grade cytokine release syndrome
- Pre-existing myeloma-related CKD/cast nephropathy
- High disease burden (CRS and tumor-lysis risk)
- Volume depletion, intercurrent infection, and concurrent nephrotoxins
Prevention
- Two-step (priming) dosing with premedication and monitoring per protocol
- Tumor-lysis prophylaxis (hydration, uric-acid-lowering therapy) in high-burden disease; infection prophylaxis
- Hydration and avoidance of additional nephrotoxins
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Vital signs and CRS grading during priming and early full doses
- Tumor lysis labs and serum creatinine/eGFR around initiation in high-burden disease
- Infection surveillance and immunoglobulin levels (hypogammaglobulinemia)
Key trials & series
- MagnetisMM-3 (Lesokhin Nat Med 2023) registrational trial
- Wen Onco Targets Ther 2024 bispecific-antibody nephrotoxicity review
- Leon-Roman Clin Kidney J 2024 immune-effector-cell AKI cohort (analogous CRS-AKI)
Clinical pearls
- Among the myeloma bispecifics, elranatamab carries a more explicit tumor-lysis as well as CRS-AKI signal—give TLS prophylaxis in high burden.
- AKI is usually CRS hemodynamics layered on myeloma kidney disease, not direct tubular toxicity.
- Two-step priming with premedication mitigates CRS and downstream AKI.
- Watch for septic AKI from BCMA-related hypogammaglobulinemia and infection.
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.
- ASCO (2021) — Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO GuidelineGrade toxicities by ASTCT criteria; manage CRS with supportive care escalating to tocilizumab with or without corticosteroids, and manage moderate-to-severe ICANS with corticosteroids and supportive care given potential for rapid decline.J Clin Oncol · PMID 34724386
- 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 (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.Elranatamab therapy in relapsed refractory multiple myeloma patients with chronic kidney disease: A case series.Marron G, Warrier N, Chan K, Augustson B · Br J Haematol · 2026 · PMID 42051159
- 2.Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.Lesokhin AM et al. · Nat Med · 2023 · PMID 37582952
- 3.Acute Kidney Injury in Cancer Immunotherapy Recipients.Joseph A et al. · Cells · 2022 · PMID 36552755
- 4.Nephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.Wen X et al. · Onco Targets Ther · 2024 · PMID 39006885
- 5.The tumor lysis syndrome.Howard SC et al. · N Engl J Med · 2011 · PMID 21561350
- 6.Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies.Leon-Roman J et al. · Clin Kidney J · 2024 · PMID 38500492
- 7.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483
Case reports & series (3)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[C · Limited][Elranatamab treatment in a refractory multiple myeloma patient on maintenance hemodialysis].Nagahama Y et al. · Rinsho Ketsueki · 2026 · PMID 41621964
- C2.[C · Limited]Efficacy and safety of bispecific antibodies in multiple myeloma patients with end-stage renal disease undergoing hemodialysis: a case report of elranatamab and a literature review.Ogiya D et al. · Ann Hematol · 2025 · PMID 41152534
- C3.[C · Limited]Elranatamab for Relapsed/Refractory Multiple Myeloma With Severe Renal Impairment Requiring Hemodialysis.Hoffmann M et al. · Hematol Oncol · 2025 · PMID 40684380