Symptomatic Multiple Myeloma Diagnosis and Treatment

Diagnostic Criteria

The International Myeloma Society recommends that symptomatic multiple myeloma be diagnosed based on the presence of end-organ damage meeting CRAB criteria (hypercalcemia, renal insufficiency, anemia, and bone lesions) 1, 2, 3
The presence of all three symptoms (anemia, bone pain, and kidney problems) confirms CRAB criteria fulfillment, indicating symptomatic multiple myeloma 2, 3
Anemia is characterized by normochromic, normocytic anemia with hemoglobin <10 g/dL or ≥2 g/dL below normal, manifesting as weakness and fatigue 2, 3
Bone pain indicates lytic lesions, severe osteopenia, or pathologic fractures from osteoclastic bone destruction 5, 3
Renal insufficiency is defined as serum creatinine >2 mg/dL or creatinine clearance <40 mL/min, often from light chain cast nephropathy 2, 6

Smoldering multiple myeloma (SMM) requires serum monoclonal protein ≥3 g/dL and/or bone marrow plasma cells ≥10% but specifically lacks any CRAB criteria or end-organ damage 1, 2, 4
Monoclonal gammopathy of undetermined significance (MGUS) requires serum monoclonal protein <3 g/dL, bone marrow plasma cells <10%, and absence of end-organ damage 1, 2, 4

The diagnosis of symptomatic multiple myeloma requires documentation of ≥10% clonal plasma cells on bone marrow examination or biopsy-proven plasmacytoma 2
Evidence of end-organ damage attributable to the plasma cell disorder is also required 2

Serum and urine protein electrophoresis with immunofixation should be performed to identify monoclonal protein 4, 6
Serum free light chain assay with kappa/lambda ratio should be performed to assess light chain production 4, 6
Complete blood count should be performed to confirm anemia 4, 6
Serum creatinine and calcium levels should be documented to assess renal function and hypercalcemia 4, 6
Bone marrow aspiration and biopsy with CD138 staining should be performed to quantify plasma cells 4, 6

Skeletal survey or whole-body low-dose CT should be performed to document lytic bone lesions 5
MRI of spine should be performed if skeletal survey is negative or spinal cord compression is suspected 6

Elderly patients may have confounding conditions that mimic myeloma, such as mild renal insufficiency from diabetes or hypertension, anemia from iron, B12, or folate deficiency, or myelodysplastic syndrome 7, 1
Osteoporosis with compression fractures may be mistaken for myeloma-related bone lesions, but long-standing progressive osteoporosis argues against active myeloma 7
Hypercalcemia from hyperparathyroidism rather than myeloma should be ruled out by checking PTH levels 7

Treatment must be initiated immediately in patients with symptomatic multiple myeloma fulfilling CRAB criteria 2, 4
The specific treatment regimen depends on transplant eligibility, but the presence of end-organ damage mandates starting therapy without delay 2