CRAB Criteria for Multiple Myeloma Diagnosis
The CRAB criteria define end-organ damage in multiple myeloma as: Calcium elevation (>11.5 mg/dL), Renal failure (creatinine >2 mg/dL or clearance <40 mL/min), Anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal), and Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures). 1
Diagnostic Requirements
Multiple myeloma diagnosis requires ≥10% clonal bone marrow plasma cells (or biopsy-proven plasmacytoma) PLUS at least one of the following: 1, 2
CRAB Criteria Specifics:
- C - Calcium elevation: Serum calcium >11.5 mg/dL 1
- R - Renal failure: Serum creatinine >2 mg/dL OR creatinine clearance <40 mL/min 1
- A - Anemia: Hemoglobin <10 g/dL OR ≥2 g/dL below the lower limit of normal 1
- B - Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures on skeletal survey 1
Alternative Myeloma-Defining Events (Beyond CRAB):
- Bone marrow clonal plasmacytosis ≥60% 1
- Involved/uninvolved serum free light chain ratio ≥100 (with involved FLC ≥100 mg/L) 1
1 focal lesion on MRI (each ≥5 mm) 1
Initial Treatment Approach
Treatment must be initiated immediately in all patients meeting CRAB criteria, as delaying therapy increases morbidity and mortality. 2
For Transplant-Eligible Patients:
- Bortezomib, lenalidomide, dexamethasone (VRd) for 3-4 cycles followed by autologous stem cell transplantation 3
- For high-risk disease (del(17p), t(4;14), t(14;16), t(14;20), gain 1q, p53 mutation): Consider daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) 3
For Transplant-Ineligible Patients (≥65 years or medically unfit):
- VRd for 8-12 cycles followed by maintenance therapy 3
- Alternative: Daratumumab, lenalidomide, dexamethasone (DRd) until progression 3
- Older regimens: Bortezomib, melphalan, prednisone (VMP) for 8-12 cycles OR melphalan, prednisone, thalidomide (MPT) 2
Special Management Considerations:
- Renal impairment: Use bortezomib-based regimens (no dose adjustment needed), avoid NSAIDs, maintain aggressive hydration 2
- Hypercalcemia: Aggressive hydration with normal saline PLUS bisphosphonates (zoledronic acid or pamidronate) 2
- Bone disease: Bisphosphonates (zoledronic acid or pamidronate) to reduce skeletal-related events 2
Critical Diagnostic Pitfalls
- CRAB criteria are not pathognomonic for multiple myeloma - lymphoma and other malignancies can present with identical features 4
- Must confirm with bone marrow showing ≥10% clonal plasma cells (use CD138 staining for accuracy) AND presence of monoclonal protein on serum/urine electrophoresis with immunofixation 1, 2
- Distinguish from MGUS: <3 g/dL monoclonal protein, <10% bone marrow plasma cells, NO CRAB criteria 1
- Distinguish from smoldering myeloma: ≥3 g/dL monoclonal protein OR ≥10% bone marrow plasma cells, but NO CRAB criteria or myeloma-defining events 1
Prognostic Implications
Among CRAB features in the novel agent era, bone disease and hypercalcemia confer the worst prognosis, while anemia and renal failure show improved outcomes with modern therapies (particularly bortezomib-based regimens for renal impairment). 5 Bone disease remains the most common CRAB feature and may have the strongest prognostic value. 5