What are the CRAB (Hypercalcemia, Renal failure, Anemia, Bone lesions) criteria?

From the Guidelines

The CRAB criteria are used to diagnose multiple myeloma, a type of blood cancer affecting plasma cells, and include hypercalcemia, renal insufficiency, anemia, and bone lesions, as defined by the International Myeloma Working Group consensus criteria 1. The CRAB criteria are essential in identifying end-organ damage caused by the abnormal plasma cells, distinguishing active myeloma requiring treatment from smoldering myeloma or monoclonal gammopathy of undetermined significance (MGUS), which typically don't require immediate intervention.

• Hypercalcemia is defined as serum calcium >11 mg/dL or 0.25 mmol/L above normal.
• Renal insufficiency means creatinine clearance <40 mL/min or serum creatinine >2 mg/dL, as measured by validated equations such as the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 1.
• Anemia is defined as hemoglobin <10 g/dL or 2 g/dL below normal.
• Bone lesions refer to one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. The presence of any one of these criteria, along with ≥10% clonal plasma cells in the bone marrow or a biopsy-proven plasmacytoma, is sufficient for a multiple myeloma diagnosis. Additional myeloma-defining events include ≥60% clonal plasma cells in bone marrow, free light chain ratio ≥100, or more than one focal lesion on MRI, as outlined in the NCCN clinical practice guidelines for multiple myeloma 1. It is crucial to note that these criteria are based on the most recent and highest quality studies, including the International Myeloma Working Group consensus criteria and the NCCN clinical practice guidelines, ensuring that the diagnosis and treatment of multiple myeloma are guided by the latest evidence-based recommendations 1.

From the Research

CRAB Criteria Overview

• The CRAB criteria consist of end-organ damage with hypercalcaemia, renal dysfunction, anaemia, and bone involvement 2
• These criteria are typically associated with multiple myeloma (MM), but can also be present in other conditions, such as lymphoma 2

Components of CRAB Criteria

• Hypercalcaemia: can occur due to tumour secretion of parathyroid hormone-related protein (PTHrP), osteolytic metastases with local release of cytokines, or tumour production of 1,25-dihydroxyvitamin D (calcitriol) 2
• Renal dysfunction: can be a result of hypercalcaemia, light chain cast nephropathy, or other factors 3, 4
• Anaemia: can be caused by bone marrow infiltration by plasma cells, renal dysfunction, or other factors 3, 4
• Bone disease: can manifest as lytic bone lesions, osteoporosis, or other bone-related complications 3, 4

Diagnostic and Prognostic Value of CRAB Criteria

• The presence of CRAB criteria can help distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma 4
• The CRAB criteria can also influence the prognosis of multiple myeloma, with some studies suggesting that hypercalcaemia and bone disease are associated with a worse prognosis 4
• However, the presence of CRAB factors may not always be associated with a poor prognosis, and novel agents may improve outcomes in patients with renal failure 4

Clinical Applications of CRAB Criteria

• The CRAB criteria are used to diagnose and risk-stratify patients with multiple myeloma 3, 5, 6
• Patients with CRAB criteria may require more aggressive treatment, including autologous stem cell transplantation and novel agent-based therapies 3, 5, 6
• The presence of CRAB criteria can also guide maintenance therapy and relapse management in patients with multiple myeloma 5, 6