What would be the treatment approach for a patient with multiple myeloma and impaired renal function?

Treatment Approach for Multiple Myeloma with Renal Impairment

Bortezomib-based regimens should be initiated immediately as first-line therapy for patients with multiple myeloma and renal impairment to rapidly reduce nephrotoxic light chains and improve renal function. 1

Initial Assessment and Diagnosis

• Evaluate renal function with:

  • Serum creatinine
  • Estimated glomerular filtration rate (eGFR)
  • Electrolytes
  • 24-hour urine collection for electrophoresis
  • Serum free light chain measurement 1

• Determine if renal impairment is due to:

  • Light chain cast nephropathy (most common)
  • Hypercalcemia
  • Volume depletion
  • Hyperuricemia
  • Nephrotoxic medications
  • Other causes (amyloidosis, monoclonal immunoglobulin deposition) 1

• Consider renal biopsy if:

  • Cause of renal insufficiency is unclear
  • Suspicion of alternative pathology (e.g., monoclonal immunoglobulin deposition disease) 1

Treatment Algorithm

1. Immediate Anti-Myeloma Therapy

First-Line Therapy:

• Bortezomib-based regimens are the cornerstone of treatment for MM with renal impairment:

  • Bortezomib + dexamethasone (VD) as base therapy 1
  • Add a third agent that doesn't require dose adjustment:
    • Cyclophosphamide (VCD)
    • Thalidomide (VTD)
    • Daratumumab (Dara-VD or Dara-VCD) 1

• Advantages of bortezomib-based regimens:

  • No dose adjustment needed for severe renal impairment or dialysis 1
  • Rapid reduction of nephrotoxic light chains 1
  • May overcome negative prognostic impact of renal impairment 1
  • Higher rates of renal recovery (up to 40-50%) 1, 2

For Transplant-Eligible Patients:

• Limit induction to 3-4 cycles before stem cell harvest 1
• Consider autologous stem cell transplantation with reduced-dose melphalan conditioning 1

For Transplant-Ineligible Patients:

• Continue bortezomib-based therapy (e.g., VMP: bortezomib, melphalan, prednisone) 1

2. IMiD-Based Regimens (Second-Line Options)

• Lenalidomide:

  • Requires dose adjustment based on renal function 1
  • Starting dose:
    • eGFR 30-60 mL/min: 10 mg daily
    • eGFR <30 mL/min: 15 mg every other day
    • Dialysis: 5 mg once daily after dialysis 1
  • Higher risk of thrombocytopenia and discontinuation in renal impairment 1, 3

• Pomalidomide:

  • Can be used at full dose (4 mg/day) regardless of renal function, including dialysis 1
  • Consider for relapsed/refractory disease 4

3. Supportive Care Measures

• Hydration: Intravenous fluids to maintain urine output of 100-150 mL/h 1
• Avoid nephrotoxic medications 1
• Correct metabolic abnormalities:
  • Hypercalcemia: IV fluids, bisphosphonates (with dose adjustment), denosumab, calcitonin 1
  • Hyperuricemia: Allopurinol or rasburicase 1
• Consider mechanical removal of light chains in severe cases:
  • Plasmapheresis or high cut-off dialysis (controversial, clinical trial setting) 1

Monitoring and Response Assessment

• Monitor serum creatinine, eGFR, and free light chains regularly
• Assess for renal recovery (improvement in eGFR)
• Evaluate myeloma response using standard criteria

Special Considerations

• Bisphosphonates in renal impairment:

  • Pamidronate: Reduce infusion rate to 20 mg/h
  • Zoledronic acid: Avoid if CrCl <30 mL/min; reduced dosing for CrCl 30-60 mL/min 1

• Relapsed/Refractory Setting:

  • Consider triplet therapy with two novel agents (proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies) 1
  • Carfilzomib may be an option for selected patients 5, 4

Common Pitfalls to Avoid

1. Delayed treatment initiation: Immediate therapy is crucial for renal recovery
2. Inadequate hydration: Maintain euvolemia to reduce cast formation
3. Inappropriate medication dosing: Adjust doses based on renal function except for bortezomib
4. Overlooking other causes of renal impairment: Address hypercalcemia, dehydration, and nephrotoxic medications
5. Underutilizing bortezomib: Should be first-line therapy in renal impairment
6. Excessive focus on mechanical removal: Anti-myeloma therapy is the primary intervention

By following this treatment approach, renal function can be preserved or improved in a significant proportion of patients with multiple myeloma and renal impairment, leading to better overall survival and quality of life.