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 initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression * Subject has measurable disease as defined by \> 0.5 g/dL serum monoclonal protein, \>10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI * Subject has a Karnofsky performance status ≥60% (\>50% if due to bony involvement of myeloma (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 childbearing potential 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 have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with FCBP even if they have had a successful vasectomy. See Appendix III: Risks of Fetal Exposure, Pregnancy Testing 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 in blood 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 the cervix or breast, or localized prostate cancer with Gleason score \< 7 with stable prostate 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 ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system 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 problem that 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, or thalidomide * Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment * Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent * Subject has previously been treated for MM * Patients with symptomatic primary amiloidosis or symptomatic secondary amiloidosis (in patients with diagnosis of múltiple myeloma