Inclusion Criteria:

- Histologically or cytologically confirmed MM

- Have received only one prior systemic chemotherapy platinum-based regimen for
advanced MM

- Measurable disease, defined at least 1 unidimensionally measurable lesion > 20 mm by
conventional techniques or > 10 mm by spiral CT scan (modified RECIST criteria)

- Disease not amenable to curative surgery

- No known brain metastasis

- Age 18 and over

- Performance status 0-2

- Life expectancy > 12 weeks

- Adequate hematologic, hepatic and renal function

- Platelet count > 75000/mm3

- Absolute granulocyte count > 1000/mm3

- Hemoglobin > 9 g/dL

- Bilirubin total < 1.5 x ULN (Upper limited normal), except patients with documented
Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dl

- AST and ALT < 2.5 x ULN ( < 5 x ULN if documented liver metastasis are present)

- Creatinine level < 2mg/dl or calculated creatinine clearance > 60 mL/min as
determined by the Cockcroft Gault equation.

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Patient must be willing and able to provide written informed consent, and the trial
have to be approved by the institutional review board at each institution

Exclusion Criteria:

- Symptomatic chronic inflammatory or autoimmune disease

- Active hepatitis B or C

- Prior treatment with tremelimumab or other anti-CTLA-4 antibody or anti-PD1,
anti-PDL-1 agents

- Clinically relevant cardiovascular disease

- History of psychiatric disabilities, potentially interfering with the capability of
giving adequate informed consent

- Uncontrolled active infections

- Other concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents

- History of other malignancies except for adequately treated basal cell carcinoma or
squamous cell skin cancer or carcinoma of cervix, unless the patient has been
disease-free for at least 5 years