A phase I/II trial of very low to low-dose continuous azacitidine in combination with standard doses of lenalidomide and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma.

Abstract

8584 Background: Azacitidine (AZA) may overcome drug resistance of relapsed or refractory multiple myeloma (RRMM).Continuous administration should maximize epigenetic effects and safety. Methods: Lenalidomide (len) 25mg (10mg if GFR 30-59 ml/min) d1-21 every 28d and dexamethasone (dex) 40mg weekly (len-dex) were combined with escalating doses of AZA from 30mg/m2 SC weekly to 50mg/m2SC twice a week. Dose limiting toxicity (DLT) was assessed during cycle 1. IMWG uniform response criteria (partial response, PR) and adapted EBMT criteria (minor response, MR) were used. Plasma activity of the AZA inactivating enzyme cytidine deaminase (CDA) was measured by HPLC at Zymo Research Corp., CA. Results: Forty patients (pts) with relapsed (n = 3) or refractory (n = 37) MM were enrolled after a median of 4 prior regimens (range 1-10). Their disease was refractory to len (n = 32), bortezomib and / or carfilzomib (n = 32), or both len and proteasome inhibitors (n = 28). The target phase II dose of 50mg/m2 SC twice a wk ...