8009 Background: Melphalan-prednisone + thalidomide (MPT) or bortezomib (MPV) are approved in frontline MM patients (pts) >65 years. Both regimens demonstrated significant benefit over MP alone in terms of PFS and OS but this benefit could be hampered by the risk of peripheral neuropathy (PN). Carfilzomib (Cfz) is a novel proteasome inhibitor that has demonstrated promising activity and favorable toxicity profile, with low rates of PN. This phase I/II study was designed to determine the maximum tolerated dose (MTD) of CMP, to assess safety and evaluate efficacy of this combination in newly diagnosed MM >65. Methods: In Phase I, Cfz was the only escalating agent starting at 20 mg/m2 (level 1) with maximal planned dose 36 mg/m2 (level 3), given IV on days 1, 2, 8, 9, 22, 23, 29, 30 for nine 42-day cycles. Oral melphalan 9 mg/m² and prednisone 60mg/m² were given on days 1 to 4, for all dose levels. Based on toxicity assessment, the study was amended to add dose level 4 (Cfz 45 mg/m2). MTD determination was b...