Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis

Patients with immunoglobulin light chain (AL) amyloidosis with cardiac or multiorgan involvement are at high risk of death during or immediately after chemotherapy with intravenous melphalan and autologous stem cell transplantation (ASCT), which is considered the most effective treatment for this disease. A risk-adapted reduction of the dose of melphalan renders ASCT feasible in patients with advanced disease at the cost of a reduced response rate and of a still-considerable mortality. 1,2 Between 1999 and 2002, we treated with oral melphalan and dexamethasone (M-Dex) 46 consecutive patients ineligible for ASCT, 67% of whom achieved a hematologic response (complete remission [CR] in 33%) in a median of 4.5 months. 3 Only 2 patients died while on treatment. A subsequent randomized study showed no difference in response rate and survival between M-Dex and ASCT. 4 However, the follow-up of patients treated with M-Dex was limited, and there was concern that response could be short-lived, resulting in reduced survival. 5 Thus, we extended the follow-up of the original cohort of patients treated with M-Dex. Median follow-up of living patients is 5.0 years (range, 3.5-6.7 years). A total of 21 patients-13 nonresponders and 8 responders-died after a median of 1.6 years (range, 0.1-5.7 years). Death was not amyloid-related in 4 patients who responded to M-Dex, whereas it was due to progressive cardiac amyloidosis in the remaining cases. Median progression-free and overall survival are 3.8 and 5.1 years, respectively (Figure Hematologic response significantly prolonged survival (Figure