Lenalidomide Treatment In Patients with AL Amyloidosis Associated End-Stage Renal Disease and Dialysis

Abstract 3022

The combination of lenalidomide and dexamethasone can produce partial and complete hematologic responses in previously treated patients with AL amyloidosis (Blood 2007; 109: 492–496). Since lenalidomide is primarily excreted unchanged by the kidney, adjustments to the starting dose of lenalidomide are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to nonmalignant conditions, lenalidomide starting dose adjustment is recommended for patients with CrCl < 60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min, and dialysis patients with creatinine clearances less than 7 mL/min, have not been studied. Here, we report on a study of patients treated with Lenalidomide alone and in combination with dexamethasone for patients with AL amyloidosis associated end-stage renal disease and dialysis. Seven patients with AL amyloidosis and dialysis dependence were treated with lenalidomide alone or with dexamethasone (ClinicalTrials.gov: NCT00091260) at Boston Medical Center. All patients received lenalidomide at 10 mg orally three times a week after dialysis from D1-21. Dexamethasone at 20 mg/week dose was added after 3 cycles of single agent lenalidomide if no hematologic response was achieved. All patients received aspirin and proton-pump inhibitor prophylaxis. Toxicity and responses were evaluated after 1, 3, 6, 9, and 12 months of treatment. Hematologic responses were based upon qualitative and quantitative measures of clonal plasma cell disease and were assessed at 3 months after initiation of treatment. Organ responses were scored according to published criteria. The median age was 61 years (range, 45 to 72); and 71% were male. Three patients (43%) had lambda clonal plasma cell dyscrasia, and 6 (86%) had cardiac involvement. Five patients were on hemodialysis and 2 on peritoneal dialysis. The median duration of dialysis-dependence prior to enrollment was 7.1 months. All patients had received prior treatment with a median number of treatment regimen of 1, and 4 (57%) had received prior high-dose melphalan and stem cell transplantation. Two (28%) patients died after enrollment, 1 after one dose and 1 after 2 cycles of protocol-directed treatment. Six of the 7 patients were evaluable for toxicities after at least 1 cycle of lenalidomide. Grade 3 or higher toxicities observed included fatigue (n=2) and neutropenia (n=2). None of the patients developed thromboembolic complications. Four of the 7 patients (n=2 due to early death and n=1 due to completion of only 1 cycle so far) were evaluable for assessment of hematologic responses. Three of 4 (75%) achieved normalization of serum free light chain ratio, however, with persistence of monoclonal gammopathy (IFE positive complete response). The median time to achievement of the best hematologic response was 6 months (range, 3–12). None of the patients required addition of dexamethasone after the 3^rd cycle. No patient developed dialysis independence. Four of the 7 patients are alive with a median follow-up of 13.4 months on the trial. In conclusion, lenalidomide is reasonably well-tolerated in patients with AL amyloidosis associated end-stage renal disease and dialysis, and can induce hematologic responses as single agent in this study of small patient population.