Is Enfortumab Vedotin Dialyzable?
Enfortumab vedotin is NOT dialyzable and can be safely administered at standard doses to patients on hemodialysis without dose adjustment.
Pharmacokinetic Rationale
Enfortumab vedotin is a large molecular weight antibody-drug conjugate (approximately 150 kDa) that is not removed by hemodialysis due to its size exceeding the pore cutoff of dialysis membranes 1. The pharmacokinetic profile shows:
- No dose adjustment required for renal impairment: Clinical pharmacology studies demonstrated no significant differences in exposure or safety of enfortumab vedotin and free MMAE (the cytotoxic payload) in patients with mild, moderate, or severe renal impairment versus normal renal function 1
- Linear, dose-proportional kinetics: The drug exhibits predictable pharmacokinetics at doses of 0.5-1.25 mg/kg, supporting consistent dosing regardless of renal function 1, 2
Clinical Evidence in Hemodialysis Patients
Multiple case reports confirm successful treatment outcomes in end-stage renal disease patients on hemodialysis:
- Complete responses documented: A 74-year-old woman on hemodialysis for complete urinary tract extirpation achieved complete response after 2 cycles of standard-dose enfortumab vedotin without grade 3 or higher adverse events 3
- Multiple successful cases: Two additional patients at New England tertiary cancer centers achieved complete responses while receiving concurrent hemodialysis, with standard dosing extrapolated from monoclonal antibody pharmacokinetics 4
Dosing Recommendations for Dialysis Patients
Use standard weight-based dosing without modification:
- First-line combination therapy: 1.25 mg/kg on Days 1 and 8 of a 21-day cycle (when combined with pembrolizumab) 5
- Monotherapy (later-line): 1.25 mg/kg on Days 1,8, and 15 of a 28-day cycle 1, 2
- No timing considerations: Dialysis timing relative to drug administration does not require adjustment, as the drug is not removed by dialysis 3, 4
Safety Monitoring Considerations
Standard toxicity monitoring applies to dialysis patients, with particular attention to:
- Peripheral neuropathy: Occurs in 56.4% (grade 1-2) and 6.8% (grade 3) of patients; baseline neurological evaluation essential 6
- Hyperglycemia: Grade 3 hyperglycemia occurs in 6.1% of patients; baseline screening and management with metformin or insulin as needed 7
- Rash: Common adverse event (48-49% incidence) requiring monitoring 5
Critical Clinical Caveat
While enfortumab vedotin itself is not dialyzable, patients with uncontrolled diabetes may be ineligible for treatment regardless of dialysis status, as hyperglycemia is a key toxicity 7. The decision to treat should prioritize the significant survival benefit (median OS 31.5 months vs 16.1 months with chemotherapy in first-line setting) against individual patient comorbidities 8.