Introduction: No standard treatment is available for relapsed or refractory amyloid light-chain (AL) amyloidosis. The efficacy of lenalidomide has been proven in patients (pts) with multiple myeloma (MM) but its role in AL amyloidosis is not yet defined. Two small phase II trials (Sanchorawala et al and Dispenzieri et al, Blood, 2007) showed that toxicity might be higher than in pts with MM and standard dosage (25 mg) had to be reduced.

Patients: Since 2006 40 pts with relapsed or refractory AL amyloidosis were treated with lenalidomide/dexamethasone (LD) at our center. Administration of at least 6 cycles was planned. The starting dosage of L was 15 mg and was adapted to renal function (15 mg every 48 hours for creatinine clearance < 40 ml/min, 15 mg 3-times a week for dialysis patients). The starting dosage of D was 20 mg (day 1 – 4) in the majority of the pts. Prophylaxis against thrombosis and infections consisted of aspirine 100 mg (n=35) or low-weight molecular heparine (n=4) and ciprofloxacine, respectively. Median age of the 40 pts enrolled was 60.5 years (range, 45–74 years). 19 patients have relapsed or become refractory after treatment with high-dose melphalan and 21 pts after melphalan-based conventional chemotherapy. 21 pts had an impaired renal function (creatinine clearance < 40 ml/min; 9 pts on dialysis) at study inclusion. Before start of LD 17 of 31 evaluable pts had an elevation of both cardiac biomarkers (cardiac troponin and brain-natriuretic peptide, Mayo Stage II, Dispenzieri et al, JCO 2004), in 10 pts one marker was elevated (Mayo stage I). The median number of previous chemotherapy regimens was 2, the median number of previous therapy cycles was 5. The median time from diagnosis to start of LD was 24 months.

Results: Median follow up is 4 months (range 1–18 months). The median number of administered LD cycles is 3 (range 1–12), 12 pts have received at least 6 cycles. 32 pts are alive. Hematological toxicity > NCI grade 2 required dose reduction of L in 10 pts. Seven pts died early during LD therapy (4 with Mayo stage II, 3 with end stage renal disease). Three pts stopped therapy due to side effects after receiving less than 3 cycles. 24 pts are still on therapy with LD. Main non-hematological toxicities were fatigue > NCI grade 2 in 14 pts, worsening of renal function in 7 pts with pre-existing renal failure (3 pts requiring dialysis) and infections > NCI grade 2 in 2 pts. Three pts developed deep vein thrombosis (all with aspirine prophylaxis and additional risk factors for thrombosis); no bleedings were reported. Liver toxicity > NCI grade 1 or worsening of polyneuropathy were not observed. Skin rash occurred in 3 pts. One pt achieved complete remission of the underlying gammopathy and 46% of evaluable pts had partial remission after a median of 3 LD cycles.

Conclusion: 40 pts with AL amyloidosis were treated uniformly with dose-reduced LD. Using prophylaxis against infections and thrombosis the treatment was feasible and not associated with undue toxicities encountered in pts with far advanced disease. The worst toxicity was observed in pts with severe impaired renal and cardiac function. The optimal dosage for these pts should be further evaluated. The hematological remission rate of 50% is encouraging in this cohort of heavily pre-treated AL amyloidosis pts. A longer follow-up period is mandated to further evaluate the efficacy in organ responses.

Disclosures: Goldschmidt:Celgene: Honoraria. Off Label Use: Lenalidomide has not been approved for treatment of patients with AL amyloidosis in Germany.

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