Lenalidomide Dosing for eGFR <10 mL/min
For patients with eGFR <10 mL/min not on dialysis, lenalidomide should be dosed at 15 mg every 48 hours (every other day) for 21 days on a 28-day cycle; for patients on hemodialysis, the dose is 5 mg once daily after each dialysis session for 21 days on a 28-day cycle. 1
Dosing Algorithm Based on Renal Function
The dosing strategy for severe renal impairment follows a clear stepwise approach based on creatinine clearance and dialysis status:
- CrCl >30 but ≤50 mL/min: 10 mg daily for 21 days per 28-day cycle 1
- CrCl <30 mL/min (not on dialysis): 15 mg every 48 hours for 21 days per 28-day cycle 1
- Hemodialysis-dependent: 5 mg once daily administered after dialysis for 21 days per 28-day cycle 1
Pharmacokinetic Rationale
Lenalidomide is renally cleared and dialyzable, making dose adjustment mandatory in severe renal impairment. 1 The drug undergoes significant renal elimination, and failure to adjust dosing can lead to drug accumulation and increased toxicity, particularly hematologic adverse events. 1
Pharmacokinetic studies demonstrate that lenalidomide is removed by dialysis, which is why the medication must be administered after dialysis sessions to prevent premature drug removal. 1
Clinical Efficacy in Severe Renal Impairment
Despite dose reductions, lenalidomide maintains therapeutic efficacy in patients with severe renal impairment:
- A phase II trial using the adjusted dosing schedule achieved an overall response rate (ORR) of 76%, with 50% partial response and 26% very good partial response. 1
- In dialysis-dependent patients specifically, the ORR was 20%, though this was lower than non-dialysis patients. 1
- Real-world experience with 23 relapsed multiple myeloma patients with CrCl <30 mL/min (56% on hemodialysis) showed an ORR of 56% with median event-free survival of 20.5 months and overall survival of 42.6 months. 2
Critical Monitoring and Dose Adjustment Strategy
Continuous dose adjustment is essential beyond initial dosing, as renal function may improve with effective myeloma treatment. 2 This creates a unique challenge where patients may become relatively underdosed as their kidney function recovers.
Key monitoring points:
- Assess renal function at the start of each cycle to determine if dose escalation is appropriate as kidney function improves. 3
- Monitor complete blood counts weekly during the first 2 cycles, then at minimum before each cycle, as hematologic toxicity (particularly neutropenia, thrombocytopenia, and anemia) is significantly increased in severe renal impairment. 1
- Pharmacokinetic studies show that patients with severe RI may experience significant decreases in drug exposure after repeated dosing due to rapid clinical improvement and enhanced drug clearance, potentially requiring dose increases. 3
Toxicity Profile and Management
The toxicity profile differs substantially based on severity of renal impairment:
- Anemia: 57.1% in dialysis patients vs 27.3-35.3% in non-dialysis severe RI 1
- Thrombocytopenia: 50% in dialysis patients vs 27.3-17.6% in non-dialysis severe RI 1
- Infections: 28.6% grade 3/4 in dialysis patients 1
- Pneumonia: 25% in severe RI vs 9% in moderate RI vs 7% in mild/no RI 1
Thromboprophylaxis with aspirin should be used in 78% or more of patients to prevent thromboembolic complications. 2
Common Pitfalls to Avoid
Do not use serum creatinine alone to assess renal function—eGFR or calculated creatinine clearance is essential, as serum creatinine may appear deceptively normal while significant renal impairment exists. 4
Do not maintain static dosing—failure to increase the dose as renal function improves with myeloma treatment can lead to subtherapeutic drug levels and treatment failure. 3, 2
Do not administer lenalidomide before dialysis—the drug is dialyzable and must be given after dialysis sessions to ensure adequate drug exposure. 1
Do not discontinue therapy prematurely for mild toxicity—dose adjustments based on individual tolerance, even with stable renal function, can maintain treatment efficacy while improving tolerability. 2
Alternative Dosing Strategy
An alternative approach of lenalidomide 25 mg every other day has shown promise in real-world experience with 18 patients, achieving an ORR of 66.5% and renal response in 61.1% without serious adverse events. 5 However, this approach lacks validation from controlled trials and should be considered only when standard dose-adjusted regimens are not feasible.
Survival Outcomes
Renal impairment remains a significant predictor of overall survival but does not significantly impact progression-free survival when appropriate dose adjustments are made. 4 Patients with decreasing eGFR showed similar 1- and 2-year PFS rates compared to those without renal impairment (HR 1.028, p=0.69), but OS was decreased (HR 1.192, p=0.04). 4
Median progression-free survival in severe RI patients ranges from 8-20.5 months, and overall survival from 20-42.6 months, demonstrating that lenalidomide remains a viable treatment option despite severe renal compromise. 5, 2