Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (BCMA/MMAF)
Belantamab mafodotin
Blenrep · Bela
A BCMA/MMAF conjugate for myeloma whose hallmark is ocular, not renal — kidney data are emerging.
MildAntibody-drug conjugate · approved 2020
Multiple myeloma
Signature kidney injury
Prerenal / Hemodynamic AKI
Renal-specific data are emerging and sparse; direct nephrotoxicity is not an established signal. In myeloma, AKI more often reflects the underlying disease (cast nephropathy, hypercalcemia, volume status) than the ADC. A case of focal segmental glomerulosclerosis after belantamab mafodotin (confounded by severe COVID-19) has been reported. The defining toxicity is ocular keratopathy (71-77% in DREAMM-2).
Source: Sabbah et al., Am J Case Rep 2024 (case); Baines et al., Clin Cancer Res 2022 (DREAMM-2)
Mechanism of kidney injury
No well-defined direct renal mechanism in humans; MMAF-based ADCs are dominated by corneal (keratopathy) toxicity from payload accumulation in proliferating epithelium. Reported renal events are case-level and often confounded by myeloma-related kidney disease (light-chain cast nephropathy, hypercalcemia) or intercurrent illness.
Clinical presentation
When present: proteinuria/nephrotic syndrome or AKI, typically requiring exclusion of myeloma-related causes; the hallmark drug toxicity is ocular (keratopathy with microcyst-like epithelial changes, blurred vision, dry eye, reduced visual acuity).
Onset
Variable; renal events reported during prolonged therapy. Ocular toxicity is often detectable within the first cycles.
Reversibility
Variable
Anticancer mechanism
Antibody-drug conjugate targeting B-cell maturation antigen (BCMA) and delivering the microtubule inhibitor monomethyl auristatin F (MMAF) via a non-cleavable linker; the charged, membrane-impermeable MMAF requires internalization, which limits bystander effect but concentrates payload in target and high-turnover tissues (notably corneal epithelium). Used in relapsed/refractory multiple myeloma.
Management
Evaluate and treat myeloma-related renal causes first; supportive care; nephrology evaluation/biopsy for unexplained proteinuria or AKI. Ocular toxicity is managed by ophthalmology-guided dose modification, not by renal parameters.
Risk factors
- Underlying myeloma kidney disease (cast nephropathy, MIDD)
- Hypercalcemia/volume depletion
- Pre-existing CKD
- Intercurrent infection
Prevention
- Monitor renal function and urine protein
- Treat myeloma-related renal drivers (light chains, calcium, volume)
- Mandatory baseline and pre-dose ophthalmologic exams under the REMS program (ocular toxicity is the dose-limiting issue)
Note · Renal data are emerging; the defining toxicity of belantamab mafodotin is ocular. Attribute renal findings cautiously given competing myeloma-related causes.
Clinical depth
Renal dose adjustment
No renal dose adjustment defined; pharmacokinetics are not expected to depend on renal clearance for an IgG-MMAF conjugate. Dosing modifications are driven by ocular findings, not renal function.
Dialyzability & ESKD dosing
Not dialyzable (large ADC; non-cleavable linker, internalization-dependent MMAF). No supplemental dosing for HD/PD.
Differential diagnosis
In a myeloma patient on belantamab with AKI/proteinuria, prioritize myeloma-related causes (cast nephropathy, light-chain deposition, hypercalcemia, dehydration) before attributing injury to the ADC; biopsy may be needed for glomerular lesions. The ocular comorbidity (keratopathy) parallels mirvetuximab and shapes overall tolerability.
Monitoring
- Ophthalmologic exam (including slit-lamp/visual acuity) at baseline and before each dose per REMS - the defining monitoring requirement
- Serum creatinine, calcium and urine protein, interpreted against myeloma disease activity
- Serum free light chains as the relevant driver of myeloma kidney disease
Key trials & series
- DREAMM-2 (Baines Clin Cancer Res 2022 FDA summary; keratopathy 71-77%)
- Sabbah Am J Case Rep 2024 (FSGS case, COVID-confounded)
Clinical pearls
- Belantamab and mirvetuximab share the ADC ocular-toxicity story (keratopathy/visual changes) - the eye, not the kidney, is the dose-limiting organ.
- Most AKI in these patients is myeloma, not drug - work up light chains, calcium and volume before blaming belantamab.
- REMS-mandated eye exams, not renal labs, govern dosing.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIGlomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (bcma/mmaf)s.
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression (payload-dependent)
Ophthalmic
Keratopathy, uveitis, retinopathy
- Keratopathy (belantamab, mirvetuximab, tisotumab)
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Interstitial lung disease (deruxtecan ADCs)
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (MMAE payloads)
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkFocal and Segmental Glomerulosclerosis in a Multiple Myeloma Patient After Belantamab Mafodotin Therapy and Severe COVID-19 Infection: A Case Report.Sabbah M et al. · Am J Case Rep 2024 · PMID 39482831Rare FSGS after belantamab mafodotin, with COVID-19 as a confounder - illustrates case-level renal data.PMIDFDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma.Baines AC et al. · Clin Cancer Res 2022 · PMID 35736811DREAMM-2 summary: keratopathy in 71-77% with a boxed ocular-toxicity warning and REMS - defines the ocular-dominant profile.PMIDAdvances in the Treatment of Relapsed and Refractory Multiple Myeloma in Patients with Renal Insufficiency: Novel Agents, Immunotherapies and Beyond.Bozic B et al. · Cancers (Basel) 2021 · PMID 34680184Reviews novel myeloma agents (including BCMA-directed therapy) in patients with renal insufficiency.PMIDAntibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know.Markides DM et al. · Ann Emerg Med 2024 · PMID 39641680Class review of ADC toxicities, including ocular-dominant MMAF agents.
Related agents
Other agents sharing the same signature kidney injury.