UARK 2006-66, Total Therapy 3B: An Extension of UARK 2003-33 Total Therapy

Inclusion Criteria: * Patients must have newly diagnosed active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. * Protein criteria must be present (quantifiable serum M-component of IgG, IgA, IgD, or IgE; urinary kappa or lambda light chain; or serum free light chain (SFLC) levels in order to evaluate response. Non-secretory patients are eligible provided the patient has \> 20% plasmacytosis OR multiple (\>3) focal plasmacytomas or focal lesions on MRI OR diffuse hyperintense signal on STIR images in the absence of hematopoietic growth factors. * Patients must have received no more than one cycle or one month of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator. * Patients must be \<75 years of age at the time of initial registration. * Ejection fraction by ECHO or MUGA ≥ 40% performed within 60 days prior to registration. * Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 50% of predicted, within 60 days of registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted if the principal investigator documents that the patient is a candidate for high dose therapy. * Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible. * All patients must be informed of the investigational nature of this study and must have signed an IRB-approved informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: * Platelet count \< 30 x 109/L, unless myeloma-related. * 5.1.2.2 Grade \> 2 peripheral neuropathy. * Hypersensitivity to bortezomib, boron, or mannitol. * Uncontrolled diabetes. * Recent (\< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias. * Evidence of chronic obstructive or chronic restrictive pulmonary disease. * Patients must not have light chain deposition disease or creatinine \> 3 mg/dl * Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years. * Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. * Pregnant or nursing women. Women of child-bearing potential must have a negative pregnancy test documented within one week of registration. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.