What is the next best step prior to initiating chemotherapy in a patient with multiple myeloma?

Tumor Lysis Syndrome Prophylaxis Before Chemotherapy in Multiple Myeloma

Prior to initiating chemotherapy in a patient with multiple myeloma, aggressive hydration with normal saline and rasburicase should be administered to prevent tumor lysis syndrome, particularly in patients with high tumor burden, renal insufficiency, or elevated LDH.

Rationale for Tumor Lysis Syndrome Prevention

Multiple myeloma patients frequently present with renal insufficiency (approximately 30% at diagnosis) and high tumor burden, placing them at significant risk for tumor lysis syndrome when chemotherapy is initiated 1. The combination of:

• Aggressive IV hydration with normal saline to maintain high urine output and prevent uric acid crystallization in renal tubules
• Rasburicase (recombinant urate oxidase) to rapidly reduce uric acid levels in high-risk patients

This represents the most appropriate pre-chemotherapy intervention for patients with multiple myeloma who have features suggesting high tumor burden or compromised renal function 2.

Why Not Alkalinization Alone

Urine alkalinization with monitoring is insufficient as a sole strategy because:

• Multiple myeloma patients often present with existing renal dysfunction (serum creatinine >2 mg/dL in many cases), making them particularly vulnerable to acute kidney injury from tumor lysis 1
• Alkalinization can paradoxically increase calcium phosphate precipitation in the setting of hyperphosphatemia that occurs with tumor lysis
• The rapid cytoreduction achieved with modern bortezomib-based triplet regimens creates substantial tumor lysis risk that requires more aggressive prophylaxis than alkalinization alone 1, 2

High-Risk Features Requiring Aggressive Prophylaxis

Patients requiring normal saline plus rasburicase include those with 2, 3:

• Renal insufficiency (creatinine >2 mg/dL or creatinine clearance <60 mL/min)
• High tumor burden (elevated LDH, β2-microglobulin >5.5 mg/L, or extensive bone marrow involvement)
• Hypercalcemia (calcium >11 mg/dL)
• Hyperuricemia at baseline

Immediate Pre-Chemotherapy Protocol

Before initiating bortezomib-based induction therapy 1, 2:

1. Establish IV access and begin normal saline at 150-200 mL/hour to achieve urine output >100 mL/hour
2. Administer rasburicase 0.2 mg/kg IV as a single dose (or 3-6 mg fixed dose) in high-risk patients
3. Monitor electrolytes (potassium, phosphate, calcium, uric acid) every 6-12 hours for the first 24-48 hours after chemotherapy initiation
4. Ensure adequate renal function monitoring with input/output measurements

Renal Protection Considerations

The European Myeloma Network emphasizes that immediate initiation of effective chemotherapy with bortezomib-based regimens is essential for patients with renal insufficiency, but this must be preceded by appropriate tumor lysis prophylaxis 1. Bortezomib itself does not require dose reduction in renal insufficiency, but preventing further renal injury from tumor lysis is critical 1.

Common Pitfall to Avoid

Do not delay chemotherapy for extended periods while attempting conservative measures alone. Once appropriate prophylaxis (normal saline + rasburicase) is initiated, chemotherapy should begin promptly, as delays in starting effective antimyeloma therapy can worsen outcomes, particularly in patients with renal involvement 1.