Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia (MILESTONE)

Inclusion Criteria:

• Age >18 years with no upper age limit with a diagnosis of newly diagnosed multiplemyeloma with indication for initiation of therapy with Eastern Cooperative OncologyGroup (ECOG) performance status 0-2

• No prior therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m2 ) and/or cyclophosphamide up to 1000 mg/m2 administered for management ofacute manifestations of multiple myeloma (hypercalcemia, renal impairment, pain) forno longer than 4 weeks prior to enrollment (pre induction). If subject received anyprior therapy, pretreatment parameters necessary for disease characterization andresponse assessment must be available.

• Measurable disease meeting at least one of the following criteria (at screening orprior to pre induction): 1) Serum monoclonal (M) protein ≥1.0 g/dl 2) ≥ 200 mg of Mprotein/24h in the urine 3) Serum free light chain ≥10 mg/dL and abnormal kappa tolambda ratio.

• Life expectancy ≥ 12 months.

• Adequate organ function - Hepatic function, with serum Alanine Aminotransferase ≤ 2.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L)within 21 days prior to initiation of therapy. Creatinine clearance (CrCl) ≥ 40mL/minute within 21 days prior to start of therapy.

• Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing andto practice contraception during treatment and for 30 days after the last dose ofbortezomib. Male subjects must agree to practice contraception and refrain fromdonating sperm during treatment and for 90 days after the last dose of bortezomib.

• All subjects must agree to comply with and be enrolled in Revlimid Risk Evaluationand Mitigation Strategy (REMS) program.

• Meet institutional criteria for autologous hematopoietic cell transplantationaccording to investigator's assessment.

• At least 30% ethnic/racial minorities will be included. If necessary, accrual willbe held of non-ethnic minority patients while continuing for ethnic minorities inorder to ensure at least 30% representation.

Exclusion Criteria:

• Diagnosis of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonalprotein, Skin changes), Waldenstrom's macroglobulinemia.

• Major surgery, radiotherapy or infection requiring therapy within 14 days ofstarting treatment.

• Pregnant or lactating females.

• Patients with uncontrolled human immunodeficiency virus, hepatitis B, hepatitis C.Patients may be eligible with Viral load is undetectable.

• Unstable angina or myocardial infarction within 4 months prior to registration, NewYork heart association Class II, III or IV heart failure, uncontrolled angina,history of severe coronary artery disease, severe uncontrolled ventriculararrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemiaor Grade 3 conduction system abnormalities unless subject has a pacemaker.

• Cerebrovascular disease manifested as prior stroke at any time or transient ischemicattack in the 12 months prior to initiation of therapy.

• Non hematologic malignancy within the past 3 years with the exception of a)adequately treated basal cell carcinoma, squamous cell skin cancer, or localizedthyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer ofGleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancerconsidered cured by surgical resection or unlikely to impact survival during theduration of the study, such as localized transitional cell carcinoma of the bladderor benign tumors of the adrenal or pancreas.

• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 21 days prior toregistration.

• Any other clinically significant medical disease or condition that, in theInvestigator's opinion, may interfere with protocol adherence or a subject's abilityto give informed consent.