Oral Cyclic Melphalan and Dexamethasone in the Treatment of Patients with AL Amyloidosis; Ineligible for High-Dose Melphalan and Stem Cell Transplantation.

Abstract 1883

Poster Board I-906

AL amyloidosis is caused by a clonal plasma cell dyscrasia and is characterized by widespread, progressive amyloid deposition leading to multisystem organ failure and death. In this disease, amyloid protein deposits are derived from monoclonal immunoglobulin light chains. Aggressive treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic remission and clinical improvement. However, only selected patients with AL amyloidosis are eligible for HDM/SCT due to amyloid-associated organ dysfunction. Recently, several investigators have demonstrated the efficacy of treatment with oral cyclic melphalan and dexamethasone (Mel/Dex) in inducing hematologic responses and improving survival for patients with AL amyloidosis. We report on 70 patients with AL amyloidosis who were treated with oral Mel/Dex. Oral melphalan was administered at 0.22 mg/kg/day for D1-4 and dexamethasone at 20-40 mg one day per week and repeated every month. The median age was 65 years (range, 46-84) and the median number of organ system involvement was 3 (range, 1–6). Majority of the patients (n=31) had predominant cardiac involvement. The reasons to select this regimen of Mel/Dex rather than HDM/SCT included severe cardiac involvement (n=23), age > 75 years (n=6), patient choice (n=6), severe autonomic neuropathy (n=6), poor functional status (n=5), treatment started by local physicians (n=9), complications of stem cell mobilization and collection precluding HDM (n=5) and others (n=11). Patients received a median of 4 cycles of Mel/Dex, (range 1-13). Hematologic responses were not evaluable in 22 patients due to early death, toxicity or patients failing to return for follow-up. Of 48 evaluable patients, 7 patients (15%) achieved a complete hematologic response. Median survival for these 70 patients has not yet been reached with a median follow-up of 17 months. Overall survival is 60% at 3 years. Thirteen of these patients received additional treatment for their disease. In conclusion, oral cyclic melphalan and dexamethasone can lead to hematologic complete responses in 15% of patients and to improvement in survival for patients with AL amyloidosis, who are not eligible for HDM/SCT.