New Diagnostic Criteria for Multiple Myeloma

Abstract

Multiple myeloma (MM) has been traditionally defined by the presence of end-organ damage, specifically, hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that are felt to be a consequence of the underlying clonal plasma cell proliferation. The International Myeloma Working Group (IMWG) has updated the diagnostic criteria for MM in 2014, adding 3 specific biomarkers that can be used to make the diagnosis in patients who do not have CRAB features. These 3 biomarkers are: presence of ≥60% clonal plasma cells in the marrow, serum free light chain (FLC) ratio ≥100 (provided involved FLC level ≥100), and more than 1 focal lesion (≥5mm in size) on magnetic resonance imaging (MRI) or whole body or spine/pelvis (Table1). Each of these biomarkers has been validated in 2 or more independent studies to have a very high risk (∼80%) of progression to symptomatic disease within 2 years. In addition, the update allows modern imaging methods including computed tomography (CT) and positron emission tomography-CT to diagnose MM bone disease. The new diagnostic criteria provide 3 important clarifications on requirements for bone and renal disease in the diagnosis of MM. First, the presence of osteoporosis, vertebral compression fractures, or bone densitometric changes in the absence of lytic lesions is not considered sufficient evidence of myeloma bone disease. Second, only suspected or proven light chain cast nephropathy is considered as meeting the renal component of the CRAB criteria. Renal disorders associated with M proteins such as light chain deposition disease, membranoproliferative glomerulonephritis, and AL amyloidosis, are considered unique diseases and not MM. Third, an estimated GFR less than 40 ml/ minute is preferred to the serum creatinine concentration for purposes of fulfilling the CRAB criteria. One of the main implications of the new diagnostic criteria is that at least one advanced imaging exam (PET-CT, low-dose whole body CT, or MRI of the whole body or spine) is needed for diagnosis in patients with suspected SMM or solitary plasmacytoma. Another implication is that patients with high risk SMM and solitary plasmacytoma who develop symptoms worrisome for progression during the course of follow up can be initiated on therapy before the onset of serious end-organ damage. Table 1International Myeloma Working Group Diagnostic Criteria for Smoldering Multiple Myeloma and Multiple Myeloma Disorder Disease Definition Smoldering multiple myeloma Both criteria must be met: • Serum monoclonal protein (IgG or IgA) ≥3gm/dL, or urinary monoclonal protein ≥500 mg per 24h and/or clonal bone marrow plasma cells 10-60% • Absence of myeloma defining events or amyloidosis Multiple Myeloma Both criteria must be met: • Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma • Any one or more of the following myeloma defining events (MDE): ○ CRAB features felt attributable to the underlying plasma cell proliferative disorder, specifically: ▪ Hypercalcemia ▪ Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >177 μmol/L (>2 mg/dL) ▪ Anemia ▪ Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT ○ Clonal bone marrow plasma cell percentage ≥60% ○ Involved: uninvolved serum free light chain (FLC) ratio ≥100 (involved free light chain level must be ≥100 mg/L) ○ >1 focal lesions on MRI (at least 5mm in size) Reproduced from Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-e548. Open table in a new tab Reproduced from Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-e548.