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Bispecific (GPRC5D×CD3)

Talquetamab

Talvey · TALQ

Bispecific (GPRC5D×CD3) · approved 2023 · 7 references

A GPRC5DxCD3 bispecific for myeloma with an emerging CRS-related acute kidney injury signal.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Moderate
Reversibility
Reversible
Onset
Early, around step-up (priming) dosing and the initial full doses when CRS risk peaks.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI.

Cytokine release syndrome is common with talquetamab (about three-quarters of patients in MonumenTAL-1, predominantly grade 1-2); CRS-associated acute kidney injury is an emerging, case-level signal that is not separately well quantified, superimposed on frequent baseline myeloma kidney disease.

Source: Chari et al., N Engl J Med 2022

Reported injury signatures: Prerenal / Hemodynamic AKI, Acute Tubular Necrosis.

Renal toxicity profile

  1. Prerenal / Hemodynamic AKIPrimary
  2. Acute Tubular NecrosisSecondary

Onset timing & rechallenge

Acute (~1–7 days) — Early — around step-up dosing and the initial full doses (peak CRS).

Mechanism of kidney injury

T-cell activation triggers cytokine release (IL-6, IFN-gamma, TNF); CRS produces a prerenal, hemodynamic pattern (vasodilation, capillary leak, hypoperfusion) that may progress to ischemic acute tubular injury. Pre-existing myeloma kidney disease (cast nephropathy, light-chain tubulopathy, reduced GFR) increases susceptibility. Unlike BCMA agents, GPRC5D's distinct on-target effects are dermatologic/mucosal rather than renal.

Clinical presentation

Creatinine rise during CRS (fever, hypotension), often on a background of myeloma-related renal impairment; oliguria in severe cases. Talquetamab also causes prominent skin, nail, and oral (dysgeusia, dysphagia, weight loss) toxicities, which are non-renal but can drive reduced intake and secondary volume depletion.

Management

Manage CRS by grade (supportive care, tocilizumab, corticosteroids) and maintain renal perfusion with fluids; hold dosing for severe CRS. Renal function generally recovers as CRS resolves; treat underlying myeloma kidney disease and address oral toxicity-related volume depletion concurrently.

Risk factors

  • Higher-grade cytokine release syndrome
  • Pre-existing myeloma-related CKD
  • Volume depletion (including from oral toxicity/poor intake) and concurrent nephrotoxins
  • High disease burden

Prevention

  • Step-up (priming) dosing with premedication and monitoring per protocol
  • Hydration and nutritional support given prominent oral toxicity; avoidance of additional nephrotoxins

Renal dose adjustment

No specific renal dose adjustment is established; talquetamab pharmacokinetics are not meaningfully renally dependent. Step-up dosing and holds for severe CRS, plus supportive management of oral toxicity, are the operative levers rather than renal dose modification.

Dialyzability & ESKD dosing

Not dialyzable—an IgG-based bispecific antibody cleared by catabolism; not removed by hemodialysis and no supplemental dosing needed. Renal replacement therapy treats AKI, not drug clearance.

Differential diagnosis

Distinguish CRS-driven prerenal/ischemic AKI from progression of underlying myeloma cast nephropathy (rising serum free light chains) and from volume depletion secondary to talquetamab's oral toxicity (poor intake, dysphagia). Timing with step-up dosing and CRS grade aids attribution.

Monitoring

  • Vital signs and CRS grading during step-up and early full doses
  • Serum creatinine/eGFR and electrolytes around dosing
  • Weight, oral intake, and hydration status (prominent dysgeusia/dysphagia)

Key trials & series

  • MonumenTAL-1 (Chari NEJM 2022) 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

  • GPRC5D's signature toxicities are skin/nail/oral, not renal—but severe dysgeusia/dysphagia can cause prerenal AKI via poor intake.
  • As with BCMA agents, AKI is mainly CRS hemodynamics on top of myeloma kidney disease.
  • Step-up dosing and tocilizumab-based CRS management may help protect the kidney by limiting CRS severity.
  • Support nutrition and hydration aggressively given the oral toxicity profile.

Anticancer mechanism

T-cell-redirecting bispecific antibody targeting GPRC5D (an orphan receptor highly expressed on malignant plasma cells) and CD3 on T cells, driving T-cell-mediated killing of myeloma cells. Used in relapsed/refractory multiple myeloma.

Note

Renal injury is an emerging, CRS-mediated (indirect) signal rather than a direct nephrotoxic effect; quantitative renal data are limited for this newer agent and largely extrapolated from bispecific/CAR-T CRS-AKI literature.

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. 1.Efficacy and safety of talquetamab in relapsed/refractory multiple myeloma and renal impairment: a quaternary cancer center cohort.Ali HM, Mazzoni S, Goel U, et al · Blood Cancer J · 2026 · PMID 42056076
  2. 2.Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.Chari A et al. · N Engl J Med · 2022 · PMID 36507686
  3. 3.Acute Kidney Injury in Cancer Immunotherapy Recipients.Joseph A et al. · Cells · 2022 · PMID 36552755
  4. 4.Nephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.Wen X et al. · Onco Targets Ther · 2024 · PMID 39006885
  5. 5.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
  6. 6.Cytokine release syndrome.Shimabukuro-Vornhagen A et al. · J Immunother Cancer · 2018 · PMID 29907163
  7. 7.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.