This protocol is an international, multicenter, comparative, open and randomized study designed to compare the safety and efficacy (in terms of response rate) from three induction chemotherapy schemes -Thalidomide/Cyclophosphamide/Dexamethasone versus Thalidomide/Dexamethasone versus Thalidomide/Melphalan/Prednisone. Finally, this study is also designed to compare the safety and efficacy (in terms of duration of response) of two maintenance chemotherapy regimens - Thalidomide/Prednisone versus Thalidomide. Each treatment arm will include 100 patients and assessments and scheduled visits will be conducted in three periods: Pre-treatment, treatment and monitoring. Security will be evaluated by monitoring all adverse events, physical examination, vital signs and biochemical studies. Response to treatment will be evaluated according to the EBMT21 criteria and will be assessed on day 1 of each cycle of induction, at the end of nine cycles of induction therapy and monthly during the first year of maintenance therapy and every 3 months thereafter.

Inclusion Criteria:

• > 65 years old and non candidate for autologous stem cell transplant

• Patient must be newly diagnosed with Multiple Myeloma according to establish criteria symptoms. Steroid pulses administration are allowed for any required emergency prior to starting induction therapy or bisphosphonates administration

• Patient must have measurable disease, defined as follows: for secretory multiple myeloma, measurable disease is defined by the presence of measurable monoclonal component in serum or in urine excretion if light chain is greater than or equal to 200 mg/24 hours(Annex 5)

• Measured ECOG < 2 state level.

• The patient must have a life expectancy greater than 3 months.

• Adequate laboratory values prior to induction treatment initiation, defined as follow:

  1. Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g / dl and absolute neutrophil count ≥ 1000/mm3. Lower values are permitted if they are due to BM infiltration.
  2. Corrected serum calcium ≤ 14mg/dl.
  3. Aspartate transaminase (AST): ≤ 2.5 x normal upper limit.
  4. Alanine transaminase (ALT):): ≤ 2.5 x normal upper limit.
  5. Total bilirubin: ≤ 1.5 x normal upper limit.
  6. Serum creatinine ≤ 2 mg / dl.

• Men (including vasectomy done) must use barrier contraception (latex condoms) when having sex with women of potential childbearing, and for at least four weeks after thalidomide last dose.

Exclusion Criteria:

• Non-secretory MM.
• Previous treatment for multiple myeloma with the exception of steroid pulses for any emergency that requires treatment before beginning the induction, administration of bisphosphonates or radiation therapy.
• Basal peripheral neuropathy higher than grade 2 within 14 days of inclusion.
• Known thalidomide hypersensitivity.
• Use of any investigational agent within 30 days prior to their inclusion.
• Known human immunodeficiency virus(HIV) infection, detectable surface antigen of hepatitis B or active infection by the hepatitis C viruses
• Myocardial infarction within 6 months prior to inclusion or heart functional class III or IV according to New York Heart Association (NYHA) heart failure, angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram or conduction system abnormalities.
• Participation in another clinical trial or receiving any investigational agent.