Inclusion Criteria:
* Adult subject aged ≥ 18 years.
* Diagnosis of smoldering myeloma as per the IMWG criteria, specifically:
* Serum monoclonal protein (IgG or IgA) of 30g/L or greater per 24 hours or urinary monoclonal protein of 500mg or greater per 24 hours and/or
* Clonal bone marrow plasma cells 10-59% with the absence of myeloma-defining events or amyloidosis
* High-risk smoldering myeloma defined as two or more out of four of the following criteria:
* M-spike greater than 2 g/dL
* An involved/uninvolved free light chain ratio greater than 20
* Bone marrow plasmacytosis greater than 20%
* Presence of any of translocation (4;14), deletion 17p, deletion 13q or 1q gain by conventional cytogenetics/fluorescence in situ hybridization (FISH) studies) and/or
* An IMWG SMM score of 9 or greater according to the IMWG risk model for smoldering multiple myeloma (SMM)
* Diagnosis of high-risk SMM made within 365 days of enrollment in the study. Note: If a patient previously had MGUS or low/intermediate SMM- the date at which high-risk SMM was diagnosed would have to be within 365 days of enrollment in the study.
Exclusion Criteria:
* Presence of any features that would meet diagnostic criteria for myeloma as per the IMWG Criteria
* Presence of extramedullary plasmacytomas
* Presence of any focal bone marrow lesions, or lytic bone lesions on imaging done prior to screening or on screening. However, presence of diffuse or patchy infiltration of the marrow (without any clear lesions) on MRI, will not be an exclusion criteria. Patients with 1 focal marrow lesion on MRI that is attributable to plasma cell dyscrasia, will be excluded from study, even if they do not meet criteria for myeloma. Patients with 1 focal marrow lesion can only be enrolled if the lesion does not appear to be related to myeloma, based on the judgement of the investigator. Use of restricted diffusion and ADC values can assist in ascertainment.
* Creatinine clearance of less than 40ml/min.
* Presence of AL Amyloidosis (the amount of workup necessary to exclude AL Amyloidosis is per the discretion of the treating investigator, however the investigator must attest that they do not believe AL Amyloidosis to be present at time of enrollment. Serum nt-PROBNP is recommended as part of evaluation in order to ascertain for cardiac amyloidosis).
Note: The Hgb cut-offs can vary between institutions (lower cut-off for Hgb University of Utah for men is a Hgb of 14.8, rendering a patient with Hgb of 12.7 as having a CRAB feature). If the Hgb is above 10g/dl but the patient meets the definition of anemia according to the IMWG criteria, by virtue of this being more than 2 g/dl below the limit of normal, the investigator can decide whether to call a patient being considered for screening as having multiple myeloma OR smoldering myeloma and allow enrollment on this study.
Given that the values used to define high-risk SMM can change, at time of enrollment, if utilizing at least 2/4 of the 2/20/20+cytogenetics criteria to enroll, participants should meet at least 2/4 of the 2/20/20. If participants had met at least 2/4 previously at some timepoint but do not meet at least 2/4 currently, they cannot be enrolled in the study.
