From the Guidelines
The most appropriate management for a patient with multiple myeloma and impaired renal function is to initiate a bortezomib-based regimen as soon as possible, such as VCD (bortezomib, cyclophosphamide, dexamethasone) or VRD (bortezomib, lenalidomide, dexamethasone), with appropriate dose adjustments, as recommended by the NCCN guidelines 1. This approach is supported by the latest evidence, which suggests that bortezomib-based regimens can be safely administered to patients with severe renal impairment and those on dialysis, without requiring renal dose adjustment 1. Key considerations in the management of these patients include:
- Aggressive hydration to maintain urine output >3 L/day
- Correction of hypercalcemia with bisphosphonates, with dose adjustment for renal function
- Avoidance of nephrotoxic agents such as NSAIDs and iodinated contrast
- Dose reduction of lenalidomide based on creatinine clearance (15 mg daily if CrCl 30-60 mL/min; 10 mg daily if CrCl <30 mL/min)
- Consideration of early hemodialysis with high cut-off dialyzers for severe renal impairment (eGFR <15 mL/min) to remove free light chains, as suggested by the European Myeloma Network 1. The goal of this comprehensive approach is to target the underlying disease with effective antimyeloma therapy, while simultaneously addressing the mechanisms of renal damage, as light chain cast nephropathy is the predominant cause of renal failure in these patients 1. Renal function should be monitored closely, as early intervention significantly improves the chances of renal recovery and overall survival. In this case, the patient's elevated free κ and λ light chains, and κ/λ free light chain ratio of 4.1, confirm the diagnosis of multiple myeloma, and the presence of myeloma cast nephropathy on kidney biopsy supports the need for prompt initiation of a bortezomib-based regimen.
From the FDA Drug Label
In the bortezomib vs dexamethasone Phase 3 relapsed multiple myeloma study, among the 62 bortezomib-treated patients who experienced ≥ Grade 2 peripheral neuropathy and had dose adjustments, 48% had improved or resolved with a median of 3. 8 months from first onset.
Retreatment in Relapsed Multiple Myeloma A single-arm trial was conducted in 130 patients with relapsed multiple myeloma to determine the efficacy and safety of retreatment with intravenous bortezomib
The most appropriate management for a patient with multiple myeloma and impaired renal function is Chemotherapy.
- Bortezomib is a chemotherapy option that has been studied in patients with relapsed multiple myeloma, including those with impaired renal function.
- The safety profile of bortezomib in patients with relapsed multiple myeloma is consistent with the known safety profile of the drug, with no cumulative toxicities observed upon retreatment 2.
- While other management options, such as Hemodialysis or Plasmapheresis, may be necessary to manage specific complications of multiple myeloma, such as renal failure or hyperviscosity syndrome, Chemotherapy is the most appropriate initial management approach for a patient with multiple myeloma and impaired renal function.
From the Research
Management of Multiple Myeloma
The patient's presentation with worsening fatigue, weight loss, anorexia, and laboratory findings consistent with multiple myeloma, including elevated free κ and λ light chains, and a κ/λ free light chain ratio of 4.1, suggests a diagnosis of multiple myeloma. The presence of myeloma cast nephropathy, as confirmed by kidney biopsy, indicates renal impairment due to the disease.
Treatment Options
- Chemotherapy: The use of chemotherapy, specifically a combination of bortezomib, lenalidomide, and dexamethasone (VRd), is a standard treatment approach for newly diagnosed multiple myeloma, as supported by studies such as 3 and 4.
- Hemodialysis: While hemodialysis may be necessary for patients with severe renal impairment, it is not a primary treatment for multiple myeloma.
- Hospice Referral: Hospice care is typically reserved for patients with advanced disease and limited life expectancy, which is not indicated in this scenario.
- Plasmapheresis: Plasmapheresis may be considered in certain cases, such as hyperviscosity syndrome, but it is not a primary treatment for multiple myeloma.
Recommended Management
Based on the evidence, the most appropriate management approach for this patient would be chemotherapy, specifically the VRd regimen, as it has been shown to improve progression-free survival and overall survival in patients with newly diagnosed multiple myeloma, as demonstrated in studies such as 3 and 5. Additionally, the use of VRd has been recommended in guidelines for the treatment of multiple myeloma, including those outlined in 4 and 6.
Considerations
It is essential to consider the patient's renal function and adjust the treatment plan accordingly. The use of lenalidomide and dexamethasone may require dose adjustments in patients with renal impairment, as noted in 7. Close monitoring of the patient's renal function and overall response to treatment is crucial to ensure optimal outcomes.