Use of melphalan (M)/dexamethasone (D)/bortezomib in AL amyloidosis.

Abstract

8024^ Background: AL amyloidosis is a monoclonal plasma cell disorder with progressive organ dysfunction and short survival. Standard non-transplant AL therapy is melphalan (M) + dexamethasone (D). As adding bortezomib (Bz) to M+ Prednisone improved outcomes in myeloma, we sought to determine if adding Bz to MD improves outcomes in AL. Methods: Eligibility: ECOG PS ≤ 3, Cr ≤ 5 mg/dL, T.Bili ≤ 2.5 × IULN, ALT/AST ≤ 3 × IULN, ANC ≥ 1.0 K/mm3, PLT ≥ 80 K/mm3, peripheral neuropathy (PN) ≤ Gr 2 (≤ 1 if painful), no lower limit for LVEF. Design: Two-stage phase II study. Stage I: 16 pts with biopsy-proven AL, light chain deposition disease (LCDD) or smoldering myeloma with amyloid (SMM). 1o endpoint: complete hematologic responses (cHR). If ≥5 cHRs observed, then 2nd stage with 17 more pts, giving 90% power to detect a true cHR rate of 50%. 2o endpoints: overall HR, organ response (OrR), and survival. Therapy: M (9 mg/m2 PO d 1-4; 6 mg/m2 if Cr > 2.5 mg/dL), Bz (1.3 mg/m2 IV d 1, 8, 15, 22; 1.0 mg/m2 if baselin...