Clinical Significance and Management of Elevated ALP in Multiple Myeloma

Diagnostic Approach

The American College of Radiology recommends determining if ALP elevation is isolated or accompanied by other liver enzyme abnormalities 1
The American Gastroenterological Association suggests considering fractionating ALP into liver, bone, and intestinal isoenzyme fractions to determine the source of elevation 2
Additional testing may include gamma-glutamyl transferase (GGT), 5′nucleotidase levels, and direct bilirubin to differentiate between hepatobiliary disease and other sources 2

The American College of Radiology recommends ultrasound as first-line investigation for abnormal liver tests 3
For predominantly cholestatic patterns (elevated ALP), imaging of the biliary tree may be necessary to determine if extrahepatic or intrahepatic cholestasis is present 1

High potency intravenous bisphosphonates are a critical component of supportive care in multiple myeloma and have been shown to reduce skeletal-related events, as recommended by the European Hematology Association 4
Bone-specific ALP is a sensitive predictor of bone metastases in patients with advanced tumors 5

Routine monitoring of liver tests should be performed before each cycle of treatment or at least monthly during therapy, as suggested by the American Gastroenterological Association 2
In patients with an elevated baseline ALP, an increase to ≥2× baseline should prompt evaluation for possible causes including cholestatic immune-mediated liver injury, tumor progression, biliary obstruction, systemic infection, bone disease, or drug-induced liver injury 6
The European Hematology Association recommends that intravenous bisphosphonates be continued with active disease and resumed after disease relapse in multiple myeloma patients with bone disease 4
Do not use serum ALP levels to determine eligibility for clinical trials in multiple myeloma patients, as ALP is commonly elevated in patients with malignancy, according to the American Gastroenterological Association 2 and 7

In patients with treatment-emergent serum ALP elevation without significant elevation in serum ALT, causes other than immune-mediated liver injury (such as worsening of bone metastases) are more likely 6
If ALP elevation is accompanied by significant ALT elevation, consider drug-induced liver injury and follow appropriate management protocols 2 and 6