A Phase II Trial of Anti-KIR in Smoldering Multiple Myeloma

Background: * Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years. * Smoldering multiple myeloma (SMM) is a premalignant plasma cell disorder characterized by monoclonal protein greater than or equal to 3 g/dL or bone marrow plasma cells greater than or equal to 10 percent in the absence of myeloma-related tissue impairment with 51 percent progression to MM at 5 years. * Current recommendations do not endorse treatment of SMM with chemotherapy. * Transplanted Natural Killer (NK) Cells have anti-myeloma activity. * Anti-KIR (IPH2101) is a monoclonal antibody that facilitates NK cell mediated killing of myeloma cells by blocking inhibitory receptors (KIR) on NK cells. Objectives: * To assess the response rate of anti-KIR(IPH2101) in patients with SMM * To evaluate the toxicity of anti-KIR(IPH2101) in patients with SMM * To evaluate the pharmacokinetic parameters and biological activity of anti-KIR (IPH2101) Eligibility: * A confirmed diagnosis of SMM * Age greater than or equal to 18 years * Eastern Cooperative Oncology Group (ECOG) performance status in the range of 0-1. * Without serious co-morbidity that would interfere with receipt of anti-KIR(IPH2101) Design: * Single-arm Phase II trial of anti-KIR(IPH2101) for patients with SMM. * All patients will have initial evaluation and confirmation of diagnosis. * Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles. * Patients will have routine blood work with serum protein electrophoresis (SPEP) and immunofixation monthly. * Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of diagnosis and correlative studies. * Patients may donate cellular products or tissues as appropriate for research purposes. * Optimal two-stage phase II design will be employed, initially enrolling 9 patients. If 3 or more have a positive outcome, then a total of 21 patients will be enrolled in this study.