The most significant change in the IMWG updated diagnostic criteria is that some patients who previously would have been diagnosed with smoldering myeloma (ie, asymptomatic myeloma) now are considered to have active myeloma, rendering them eligible for earlier treatment. Having 60% or greater clonal plasma cells on bone marrow biopsy now places patients in the active category, as does a ratio of involved to uninvolved serum free light chains that is greater than or equal to 100. Additionally, the updated guidelines include more sensitive imaging for bone changes. Historically, a plain radiographic series of X-rays was performed to detect lytic lesions. Newer imaging techniques have greater sensitivity than radiographic bone survey for the detection of multiple myeloma bone lesions, and the IMWG updated criteria clarify that clear evidence of 1 or more sites of osteolytic bone destruction (≥5 mm in size) seen on computed tomography (CT; including low-dose whole-body CT) or positron emission tomography (PET)–CT does fulfill the criteria for bone disease in multiple myeloma, and should be regarded as meeting the CRAB criteria (ie, (hyperCalcemia, Renal failure, Anemia, Bone lesions) irrespective of whether the lesions can be visualized on skeletal radiography. The IMWG recommends that PET-CT, low-dose whole-body CT, or magnetic resonance imaging of the whole body or spine be performed in all patients with suspected smoldering multiple myeloma, with the exact imaging modality determined by availability and resources. We generally use PET-CT.

The IMWG updated criteria provide physicians with an opportunity to intervene earlier in the disease process, before patients develop end-organ damage or truly symptomatic multiple myeloma. The practical effect is also to extend the workup of patients who are sent to a hematologist with anemia or a degree of proteinuria, for instance. Thus, we are now able to identify patients who would not have been likely to remain in the smoldering category for very long. Patients who do fall in the smoldering category in the current IMWG system can be further subdivided into 3 groups (ie, low risk, intermediate risk, high risk) for progression to active myeloma. At present, that determination is based on the size of the protein spike, whether the light chain ratio is abnormal or not, and the percentage of plasma cells in the bone marrow. Low-risk patients have about a 20% risk of progression from smoldering to active myeloma within 5 years, whereas high-risk patients have a 75% or greater risk of progression to active myeloma within 5 years. The only opportunity to be treated for smoldering multiple myeloma is in clinical trials, and only patients with high-risk smoldering myeloma may be included in some investigational protocols.