Introduction: Daratumumab (DARA) is a human IgG1κ monoclonal antibody that binds with high affinity to a unique epitope on CD38. DARA monotherapy has shown promising activity in relapsed and/or refractory multiple myeloma (MM) patients with a median of 5 prior lines of therapy in two clinical studies (Study GEN501; Lokhorst HM. J Clin Oncol. 2014;32 Suppl:abstr 8513 and Study MMY2002; Lonial S. J Clin Oncol. 2015;33 Suppl:abstr LBA8512). The aim of this analysis was to identify proteins indicative of DARA’s multiple mechanisms of action (MOA) and potential predictive pharmacodynamic response markers. A broad aptamer based proteomics platform (SomaSCANTM) evaluated clinical serum samples at study entry and during treatment to determine proteins and biological pathways associated with DARA MOA or clinical response.