Multiple Myeloma: How Do We Actually Diagnose It?
In the last posts, we covered MGUS and smoldering myeloma — two conditions where abnormal plasma cells are present but there is no end-organ damage; i.e body hasn't yet been significantly harmed. Today, we cross that threshold into active multiple myeloma: the point where the disease requires treatment.
Multiple myeloma is a cancer of plasma cells, the immune cells that produce antibodies. An abnormal clone proliferates in the bone marrow, producing non-functional M protein and eventually crowding out normal blood cell production — causing damage throughout the body.
The Diagnostic Criteria
Active multiple myeloma requires two things:
Clonal bone marrow plasma cells ≥ 10% (or a biopsy-proven plasmacytoma)
At least one myeloma-defining event (MDE) — evidence that the disease is actively causing harm, or is at very high risk of doing so
That second part is where the nuance lies.
Myeloma-Defining Events: CRAB + SLiM
For decades, myeloma was defined by the CRAB criteria — the classic signs of end-organ damage:
C — Hypercalcemia: serum calcium > 11 mg/dL or > 1 mg/dL above the upper limit of normal
R — Renal insufficiency: creatinine > 2 mg/dL or creatinine clearance < 40 mL/min
A — Anemia: hemoglobin < 10 g/dL, or > 2 g/dL below normal
B — Bone lesions: one or more osteolytic lesions on imaging
Any one of these, in a patient with ≥ 10% clonal plasma cells, establishes the diagnosis.
In 2014, the IMWG expanded the criteria to include the SLiM biomarkers — three findings that indicate such high short-term risk that waiting for CRAB features is no longer justified:
S — Sixty percent or more clonal plasma cells in the bone marrow
Li — Light chain ratio ≥ 100: the involved free light chain is more than 100 times the uninvolved chain
M — MRI with ≥ 2 focal lesions of at least 5 mm on whole-body imaging
Meeting any one of these — even without CRAB — is now enough to diagnose active myeloma. This reclassified many high-risk smoldering myeloma patients and opened the door to earlier treatment.
The Basic Workup
When myeloma is suspected, evaluation includes serum protein electrophoresis (SPEP), immunofixation, free light chains, CBC, and metabolic panel. A bone marrow biopsy is essential to confirm diagnosis and send for cytogenetics/FISH, which guide prognosis and treatment decisions. For imaging, whole-body low-dose CT or PET-CT is now preferred over plain X-rays.
The Takeaway
Active multiple myeloma is diagnosed when clonal bone marrow plasma cells reach ≥ 10% plus at least one myeloma-defining event — either CRAB end-organ damage or a SLiM biomarker. The 2014 update was a pivotal shift, allowing earlier intervention for the patients at highest risk. Getting the diagnosis right, at the right time, is everything.
For background, check out the previous posts on SPEP, free light chains, MGUS, and smoldering myeloma.
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