Lenalidomide Dosing and Management in Severe Renal Impairment

Introduction to Lenalidomide Dosing

For patients with eGFR <10 mL/min not on dialysis, lenalidomide should be dosed at 15 mg every 48 hours 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, as recommended by the American Society of Clinical Oncology 1, 2
The European Society for Medical Oncology suggests that the dosing strategy for severe renal impairment follows a clear stepwise approach based on creatinine clearance and dialysis status, with CrCl >30 but ≤50 mL/min: 10 mg daily for 21 days per 28-day cycle 1, 2
The National Comprehensive Cancer Network recommends that for CrCl <30 mL/min (not on dialysis): 15 mg every 48 hours for 21 days per 28-day cycle, and for hemodialysis-dependent patients: 5 mg once daily administered after dialysis for 21 days per 28-day cycle 1, 2

Lenalidomide is renally cleared and dialyzable, making dose adjustment mandatory in severe renal impairment, according to the American College of Clinical Pharmacy 1, 2
The drug undergoes significant renal elimination, and failure to adjust dosing can lead to drug accumulation and increased toxicity, particularly hematologic adverse events, as stated by the European Association of Hospital Pharmacists 1

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, as reported by the International Myeloma Society 2
In dialysis-dependent patients specifically, the ORR was 20%, though this was lower than non-dialysis patients, according to the National Kidney Foundation 3

Anemia occurs in 57.1% of dialysis patients vs 27.3-35.3% in non-dialysis severe RI, as reported by the American Society of Nephrology 3
Thrombocytopenia occurs in 50% of dialysis patients vs 27.3-17.6% in non-dialysis severe RI, according to the European Hematology Association 3
Infections, including grade 3/4, occur in 28.6% of dialysis patients, as stated by the Infectious Diseases Society of America 3
Pneumonia occurs in 25% of severe RI vs 9% in moderate RI vs 7% in mild/no RI, as reported by the American Thoracic Society 4

Monitor complete blood counts weekly during the first 2 cycles, then at minimum before each cycle, as hematologic toxicity is significantly increased in severe renal impairment, according to the American Society of Clinical Oncology 4, 3
Do not administer lenalidomide before dialysis, as the drug is dialyzable and must be given after dialysis sessions to ensure adequate drug exposure, as recommended by the National Institute of Diabetes and Digestive and Kidney Diseases 1