Credit: Chad McNeeley
The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.
The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.
This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.
Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.
“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 [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.
“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.”
Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.
“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,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”
The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.
Definition of MM
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:
- Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
- Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
- Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
- Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
- Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.
- One or more of the following biomarkers:
- Clonal bone marrow plasma cell percentage ≥60%.
- Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
- >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.
*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone
marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.
Definition of smoldering MM
Both of the following criteria must be met:
- Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
- Absence of myeloma defining events or amyloidosis.
