What are typical calcium levels in patients with multiple myeloma?

Typical Calcium Levels in Multiple Myeloma

Hypercalcemia in multiple myeloma is defined as a corrected serum calcium level greater than 11.5 mg/dL (2.9 mmol/L) and is considered a defining diagnostic criterion for the disease.1

Diagnostic Criteria and Calcium Levels

• Hypercalcemia is one of the four CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) used to diagnose symptomatic multiple myeloma requiring treatment 1
• The threshold for hypercalcemia in multiple myeloma is defined as:
  • Serum calcium >11.5 mg/dL (2.9 mmol/L) according to the International Myeloma Working Group criteria 1
  • Treatment is typically initiated when calcium levels exceed 11.0 mg/dL 1

Prevalence and Clinical Significance

• Approximately 19.5-23.1% of newly diagnosed multiple myeloma patients present with hypercalcemia at diagnosis 2, 3
• Hypercalcemia remains an adverse prognostic factor even in the era of novel antimyeloma therapies 2
• Patients with hypercalcemia have:
  • Higher risk of early death (twofold increase) 2
  • Shorter progression-free survival (PFS) and overall survival (OS) 3
  • More frequent association with high-risk cytogenetics 2

Measurement Considerations

• Corrected calcium measurements should be used rather than total calcium, as multiple myeloma patients often have low albumin levels 3
• However, there are important caveats regarding calcium measurement in multiple myeloma:
  • Ionized calcium may be more accurate than corrected calcium for detecting true hypercalcemia in multiple myeloma patients 4
  • Sensitivity of corrected calcium in identifying hypercalcemia (defined by elevated ionized calcium) is only 36% in multiple myeloma patients compared to 76% in other cancer patients 4
  • Paraproteins in multiple myeloma may bind calcium, potentially causing pseudohypercalcemia in some cases 5

Disease Progression and Calcium Levels

• Development of hypercalcemia (>11.5 mg/dL) not attributable to other causes is considered a criterion for disease progression in multiple myeloma 1
• Hypercalcemia is often associated with other poor prognostic features:
  • Anemia and thrombocytopenia 2
  • Reduced renal function (lower eGFR) 2
  • Advanced ISS stage 2
  • Presence of lytic bone lesions 2

Clinical Pitfalls

• Be aware of pseudohypercalcemia, a rare phenomenon where total calcium is elevated but ionized calcium remains normal due to binding of calcium to abnormal immunoglobulins 5
• When pseudohypercalcemia is suspected (elevated calcium without typical symptoms), measuring ionized calcium is recommended to avoid unnecessary and potentially toxic treatments 5, 4
• Corrected calcium levels better reflect disease severity than uncorrected levels and should be used for prognostic assessment 3