This research study is being done to see if combining the investigational chemotherapy drug, MEDI-551 with the known anti-myeloma drugs, Lenalidomide and Dexamethasone will reduce your myeloma cancer stem cells.

To explore the effect of Lenalidomide, dexamethasone and Medi-551 on multiple myeloma cancer stem cells (CSCs). Myeloma CSCs will be assessed by a clonogenic assay from the bone marrow and flow cytometry from peripheral blood.

Inclusion Criteria:

• Age 18 to 100 years at the time screening
• Symptomatic, previously untreated (with exception of corticosteroids) secretory myeloma
• Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Patient must agree to take Lenalidomide with low dose dexamethasone as their initial therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy of >6 months
• Serum creatinine ≤ 2
• ANC≥1000
• Platelets ≥ 50,000
• Total bilirubin ≤ 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x ULN
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin)

Exclusion Criteria:

• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of patient safety or study results.
• Concurrent enrollment in another clinical study, except for non-interventional, observational studies.
• Any chemotherapy, immunotherapy, biologic, investigational, for treatment of multiple myeloma other than Lenalidomide and dexamethasone.
• Previous monoclonal antibody (mAb) or other treatment specifically directed against cluster of differentiation antigen 19 (CD19).
• History of serious allergy or reaction to any component of the MEDI-551 formulation that would prevent administration.
• Previous systemic cancer therapy for myeloma.
• Any active secondary malignancy.
• Human immunodeficiency virus (HIV) positive serology or acquired immune deficiency syndrome.
• Active hepatitis B as defined by seropositivity for hepatitis B surface antigen. Or patients with positive hepatitis B core antibody titers.
• Patients with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis.
• Documented current central nervous system involvement by multiple myeloma.
• Previous medical history or evidence of an intercurrent illness that may, in the opinion of the investigator, compromise the safety of the patient in the study.
• Diagnosis of plasma cell leukemia
• Diagnosis of POEMS syndrome
• Diagnosis of Amyloidosis
• Diagnosis of non-secretory myeloma