GEM-CLARIDEX: Ld vs BiRd

Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent
• Subject is >=65 years at the time of signing the consent form
• Subject has histologically confirmed MM that has never before been treated
• Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiationof study treatment except for corticosteroids with a maximum allowed dosage equivalentto three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patientsmay have received prior adjuvant antiresorptive therapy (i.e., pamidronate orzoledronic acid) as routine care, or radiation therapy as palliation for pain and/orspinal cord compression
• Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10mg/dL involved serum free light chain (either kappa or lambda) provided that the serumfree light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/ormeasurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by eitherCT scanning or MRI
• Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement ofmyeloma (see Appendix IV)
• Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin)
• If subject is a female of childbearing potential (FCBP), ( A female of childbearingpotential is a sexually mature woman who:

1. has not undergone a hysterectomy or bilateral oophorectomy; or
2. has not been naturally postmenopausal for at least 24 consecutive months (i.e.,has had menses at any time in the preceding 24 consecutive months). She must havea negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mLwithin 10 - 14 days prior to and again within 24 hours of prescribinglenalidomide (prescriptions must be filled within 7 days) and must either committo continued abstinence from heterosexual intercourse or begin TWO acceptablemethods of birth control, one highly effective method and one additionaleffective method AT THE SAME TIME, at least 28 days before she starts takinglenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agreeto use a latex condom during sexual contact with FCBP even if they have had asuccessful vasectomy. See Appendix III: Risks of Fetal Exposure, PregnancyTesting Guidelines and Acceptable Birth Control Methods

• Subject has a life expectancy ≥ 3 months
• Subjects must meet the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)
• Hemoglobin ≥ 7 g/dL
• Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration)
• Serum SGOT/AST <3.0 x upper limits of normal (ULN)ç
• Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
• Serum total bilirubin <2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

• Subject has immeasurable MM (no measurable monoclonal protein, free light chains inblood or urine, or measureable plasmacytoma on radiologic scanning)
• Subject has a prior history of other malignancies unless disease-free for ≥ 5 years,except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of thecervix or breast, or localized prostate cancer with Gleason score < 7 with stableprostate specific antigen (PSA) levels
• Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI),Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventriculararrhythmias, electrocardiographic evidence of acute ischemia or active conductionsystem abnormalities
• Female subject who is pregnant or lactating
• Subject has known HIV infection
• Subject has known active hepatitis B or hepatitis C infection
• Subject has active viral or bacterial infections or any coexisting medical problemthat would significantly increase the risks of this treatment program
• Subject is unable to reliably take oral medications
• Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, orthalidomide
• Subject has a history of thromboembolic event within the past 4 weeks prior toenrollment
• Subject has any clinically significant medical or psychiatric disease or conditionthat, in the investigator's opinion, may interfere with protocol adherence or asubject's ability to give informed consent
• Subject has previously been treated for MM
• Patients with symptomatic primary amiloidosis or symptomatic secondary amiloidosis (inpatients with diagnosis of múltiple myeloma