Lenalidomide and Dexamethasone Versus Melphalan Prednisone and Lenalidomide Versus Cyclophosphamide, Prednisone and Lenalidomide in Elderly Multiple Myeloma Patients

Inclusion Criteria: * Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements. * Patient has given voluntary written informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. * Patient is 65 years old or older at the time of signing the informed consent or younger patients not candidate to high dose therapy * Female patient is either post-menopausal or surgically sterilized or, if at child-bearing potential†, must: * understand that the study medication could have an expected teratogenic risk * Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception\* * Implant\*\* * Levonorgestrel-releasing intrauterine system (IUS)\*\* * Medroxyprogesterone acetate depot * Tubal sterilisation * Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses * Ovulation inhibitory progesterone-only pills (i.e., desogestrel) Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception. * prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection * Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. * Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence \- Male subjects must * Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception. * Agree not to donate semen during study drug therapy and for one week after end of study drug therapy. \- All subjects must * Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy. * Agree not to share study medication with another person and to return all unused study drug to the investigator. \- Patient was previously diagnosed with symptomatic MM based on standard criteria, and has measurable disease, defined as follows: * Secretory myeloma: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours; * Non-secretory myeloma: \> 30% plasma cells in the bone marrow and at least one plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan). * Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country. * Patient has a Karnofsky performance status \_ 60%. * Patient has a life-expectancy \> 6 months * Patients must have a adequate cardiac function * Patients must have adequate pulmonary function * Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1): * Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test. * Absolute neutrophil count (ANC) ≥1.0 x 109/L without the use of growth factors. * Corrected serum calcium ≤14 mg/dL (3.5 mmol/L). * Aspartate transaminase (AST): ≤2.5 x the upper limit of normal (ULN). * Alanine transaminase (ALT): ≤ 2.5 x the ULN. * Total bilirubin: ≤1.5 x the ULN. * Calculated or measured creatinine clearance: ≥30 mL/minute Exclusion Criteria: * Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; \< to the equivalent of dexamethasone 40 mg/day for 4 days). * Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study. * Pregnant or lactating females. * Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥3 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)