A Randomized Phase Iii Trial of Melphalan and Dexamethasone (mdex) Versus Bortezomib, Melphalan and Dexamethasone (bmdex) for Untreated Patients with Al Amyloidosis

Background. The combination of melphalan and dexamethasone (MDex) is considered standard treatment for patients with AL amyloidosis who are not eligible for autologous stem cell transplant at most referral centers. When full-dose (40 mg) dexamethasone can be combined with melphalan, hematologic response is achieved in three fourths of patients, with complete remissions (CRs) in 30% of cases and prolonged survival (median >7 years). Several studies showed that bortezomib is highly effective in AL amyloidosis with response rates as high as 80-90%, with 50-60% CRs, when used in combinations with alkylating agents and dexamethasone, suggesting that these regimens could replace current standard of care in AL amyloidosis. A recent case-control study indicated that the addition of bortezomib to MDex (BMDex) does not overcome the poor prognosis of patients with advanced cardiac involvement. Here we report the first interim analysis of a multicenter randomized phase III trial comparing MDex and MDex with the addition of bortezomib (BMDex) in newly-diagnosed AL amyloidosis ongoing in Europe and Australia (EMN-03 study, NCT01277016).