Updated Multiple Myeloma Criteria Could Lead to Earlier Diagnosis

The International Myeloma Working Group (IMWG) recently updated its criteria for diagnosing multiple myeloma, a blood cancer that forms in plasma cells. Multiple myeloma is always preceded by two asymptomatic conditions—monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)—so it is usually not diagnosed until the patient suffers organ damage. The new guidelines were published in the journal Lancet Oncology.

"The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with SMM who have an ‘ultra-high’ risk of progression to multiple myeloma," said S. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic and lead author of the guidelines, in a prepared statement. "These biomarkers are associated with the near inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients."

The new guidelines were developed by a worldwide group of more than 180 myeloma researchers, and the process entailed updating the “definition of multiple myeloma for diagnostic purposes to include validated biomarkers in addition to the current clinical symptoms used for diagnosis, which include elevated blood calcium levels, kidney failure, anemia, and bone lesions," Rajkumar explained. Updated guidelines were needed in part to “take into account the substantial changes to laboratory testing and imaging used in the diagnosis of multiple myeloma that have happened since the initial publication of the IMWG diagnostic criteria,” the researchers wrote. The new criteria recommend using CT and PET-CT scans to identify bone lesions, which will enable more accurate diagnosis of multiple myeloma and intervention before fractures or other serious problems arise. Also, they recommend better estimation of the extent of renal damage by using creatinine clearance and serum creatinine measurements.

Of particular note to laboratorians, the new criteria incorporate the use of free light chain (FLC) assays. About one third of people with MGUS, 70% of those with smoldering multiple myeloma, and more than 90% of those with multiple myeloma “have altered FLC ratios that indicate excess production of a clonal FLC by the proliferating plasma cell population,” the authors explained. “The presence of an abnormal FLC ratio, and the extent to which the FLC ratio is abnormal predict risk of progression in MGUS, smoldering multiple myeloma, amyloid light-chain amyloidosis, and solitary plasmacytoma.”

The new guidelines were widely publicized and could have far-reaching implications for people who otherwise would be diagnosed much later. "We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease."