This protocol is a national, multicenter, comparative, open-label, randomized trial comparing the progression free survival (PFS) of two pre-transplant conditioning regimens (BUMEL versus. MEL-200).

A total of 460 patients will be enrolled in the study. Scheduled evaluations and study visits will take place during the pre-treatment, treatment and follow-up periods.

The pre-treatment period includes the screening visit in which participants provide informed consent in writing in order to take part in the study. The patient is then assessed to determine his/her eligibility. The selection process will begin 21 days before the first dose of medication is administered (days -21 to 0). During the treatment period, eligible patients will be included in the study and given six cycles of induction treatment with bortezomib/ lenalidomide / dexamethasone (VRD-GEM). Each cycle will last 28 days, during which SC bortezomib will be administered on days 1, 4, 8 and 11, oral lenalidomide on days 1-21 of each cycle, and oral dexamethasone on days 1-4 and 9-12 of the cycle.

After the first three induction cycles, and in the absence of progression or unacceptable toxicity, peripheral blood hematopoietic stem cells will be mobilized and collected using G-CSF for later autologous transplantation. Patients will be randomized in a 1:1 allocation ratio to receive conditioning treatment with MEL-200 versus BUMEL. Randomization will take place at the beginning of the study, once the screening is complete and the patient's eligibility verified. Three months after transplantation, patients will receive two cycles of consolidation treatment with VRD-GEM at the same doses administered during induction treatment.

Once the treatment phase is complete, patients will begin the follow-up phase in which they will be visited every three months to evaluate disease progression and survival

Inclusion Criteria:

• The patient must, in the opinion of the investigator, be capable of complying with all requirements of the trial
• Have signed the informed consent form
• Be between 18 and 65 years of age and a candidate for autologous stem cell transplant
• Have an ECOG Performance Status > 2 (or 3 if the ECOG is due to myeloma)
• Newly diagnosed patient with symptomatic multiple myeloma based on standard criteria, who has not received any prior chemotherapy treatment for Multiple Myeloma.
• Patient must have measurable disease, defined by the following criteria:

For secretory MM, measurable disease is defined by any quantifiable value of serum M-protein (IgG ≥ 10 g/L or IgA > 5 g/L) and/or, when applicable, an excretion of light chain in urine ≥ 200 mg/24 hours.

For oglio- or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas, which is determined by clinical exam or radiographic techniques.

• Life expectancy > 3 months.
• The patient must have the following laboratory values in the 21 days prior to initiation of treatment (day 1, cycle 1):

Platelet count ≥ 100 x 109/L and absolute neutrophil count of ≥ 1.0 x 109/L Corrected serum calcium < 14 mg/dL. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN).

Total bilirubin within normal limits. Serum creatinine ≤ 2 mg/dL

- Women of childbearing potential and men (including vasectomized men whose partners are women of childbearing potential), must use two methods of contraception during the entire course of treatment, during dose interruptions and for up to three months after receiving the final dose

Exclusion Criteria:

• Non-secretory myeloma without measurable plasmacytomas.
• Patients who have undergone prior treatment for multiple myeloma, with the exception of emergency treatment using steroid pulses, bisphosphonates, or radiotherapy received before beginning induction treatment.
• Peripheral neuropathy ≥ grade 2 in the 21 days prior to inclusion.
• Known hypersensitivity to bortezomib, boric acid, mannitol or lenalidomide.
• Patients that have received any investigational agent in the 28 days prior to inclusion in the study.
• Patients who have had a myocardial infarction in the six months prior to inclusion in this study or who are a class III or IV according to the New York Heart Association (NYHA) functional classification system, heart failure, unstable angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram, or nervous system disorders.
• Patients currently enrolled in another clinical trial or receiving any type of investigational agent.
• Patients who are seropositive for HBV, HCV or HIV.