The purpose of this study is to evaluate the efficacy (disease response) and safety of mapatumumab in combination with bortezomib and bortezomib alone in subjects with relapsed or refractory multiple myeloma (MM).

Inclusion Criteria:

• Diagnosed with multiple myeloma that is refractory or has relapsed after treatment
• Measurable serum and/or urine M-protein
• Failed 1 or 2 prior therapies for multiple myeloma
• 18 years of age or older

Exclusion Criteria:

• Received more than 2 prior therapies for multiple myeloma.
• Previous cancer therapies (chemotherapy, biologic therapy, radiation therapy or immunosuppressants) within the last 3 weeks
• Received monoclonal antibodies within the last 3 weeks (chimeric or murine) or 8 weeks (human or humanized)
• Received investigational (not yet approved by a regulatory authority) agent to treat multiple myeloma within the last 4 weeks
• Subjects who received a stem cell transplant using cells from themselves in the past 16 weeks
• Subjects who received a stem cell transplant using cells from another individual
• Previously treated with bortezomib or mapatumumab
• Known HIV, hepatitis-B, hepatitis-C, or hepatitis A infection
• Infection requiring antibiotics or hospitalization within the last 2 weeks
• Major surgery within the last 4 weeks
• Diagnosis with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes)
• History of other cancers within the past 5 years
• Pregnant or breast-feeding women