What is the initial treatment approach for multiple myeloma?

From the Guidelines

The initial treatment approach for multiple myeloma should involve a lenalidomide- or bortezomib-containing regimen, with the choice of regimen depending on patient-specific factors such as renal function and planned subsequent treatment, as recommended by the Mayo Clinic Proceedings 1.

Key Considerations

• For standard-risk patients, lenalidomide or bortezomib in combination with dexamethasone are suitable initial therapies, with advantages including manageable adverse effects and low 1-year mortality rates 1.
• Bortezomib-based regimens are preferred in patients with renal failure at presentation due to the primarily nonrenal clearance of these drugs and the rapid responses seen with 3-drug combinations 1.
• The European Myeloma Network recommends novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients, with induction therapy including a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone, or with cyclophosphamide and dexamethasone 1.

Treatment Approach

• The treatment approach should be individualized based on patient-specific factors, including renal function, planned subsequent treatment, and overall health status.
• Supportive care, including bisphosphonates, thromboprophylaxis, and antimicrobial prophylaxis, is essential to prevent skeletal complications and manage the disease's inherent genetic heterogeneity.
• Treatment response should be assessed after 2-3 cycles using serum and urine protein electrophoresis, serum free light chains, and sometimes imaging, to determine the effectiveness of the chosen regimen and guide subsequent treatment decisions.

Recent Guidelines

• The European Myeloma Network recommendations, published in 2014, provide a comprehensive framework for the evaluation and treatment of newly diagnosed patients with multiple myeloma, including recommendations for risk stratification, induction therapy, and supportive care 1.
• The Mayo Clinic Proceedings guidelines, published in 2009, provide additional guidance on the management of newly diagnosed symptomatic multiple myeloma, including recommendations for initial therapy and subsequent treatment 1.

From the FDA Drug Label

The MAIA trial compared treatment with DARZALEX 16 mg/kg in combination with lenalidomide and low-dose dexamethasone (DRd) to treatment with lenalidomide and low-dose dexamethasone (Rd) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant. Lenalidomide (25 mg once daily orally on Days 1–21 of repeated 28-day [4-week] cycles) was given with low dose oral or intravenous dexamethasone 40 mg/week (or a reduced dose of 20 mg/week for patients >75 years or body mass index [BMI] <18.5).

The initial treatment approach for multiple myeloma includes combination therapy with daratumumab, lenalidomide, and dexamethasone (DRd) for patients ineligible for autologous stem cell transplant, as demonstrated by the MAIA trial 2 and 2.

• Key components of this regimen include:
  • Daratumumab 16 mg/kg
  • Lenalidomide 25 mg once daily orally on Days 1–21 of repeated 28-day cycles
  • Low-dose dexamethasone 40 mg/week (or a reduced dose of 20 mg/week for patients >75 years or BMI <18.5) This combination has shown to improve progression-free survival (PFS) and overall survival (OS) compared to lenalidomide and dexamethasone alone.

From the Research

Initial Treatment Approach for Multiple Myeloma

The initial treatment approach for multiple myeloma typically involves a combination of therapies. Key points to consider include:

• The use of lenalidomide and dexamethasone as a reference treatment for patients with newly diagnosed myeloma 3
• The addition of bortezomib to lenalidomide and dexamethasone (VRd regimen) has shown significant efficacy in improving progression-free survival and overall survival in patients with newly diagnosed multiple myeloma 3
• Lenalidomide-based regimens are effective as induction therapy in patients with newly diagnosed multiple myeloma 4
• The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a standard of care for most patients with newly diagnosed multiple myeloma, with maintenance until progression 5

Treatment Options and Considerations

Treatment options and considerations for multiple myeloma include:

• The use of low-dose lenalidomide and dexamethasone therapy after melphalan-prednisolone induction in elderly patients with newly diagnosed multiple myeloma 6
• The potential for adding a monoclonal antibody to the RVD backbone to deepen responses and provide longer disease control 5
• The importance of optimizing induction therapy to provide longer-term disease control and improve survival outcomes 5
• The need for further research on the best treatment options for patients who relapse while receiving lenalidomide as part of their frontline treatment 7

Key Findings and Recommendations

Key findings and recommendations for the initial treatment approach for multiple myeloma include:

• The VRd regimen is a recommended initial treatment approach for patients with newly diagnosed multiple myeloma 3
• Lenalidomide and dexamethasone is a reference treatment for patients with newly diagnosed myeloma 3
• RVD is a standard of care for most patients with newly diagnosed multiple myeloma, with maintenance until progression 5
• Low-dose lenalidomide and dexamethasone therapy may be a viable option for elderly patients with newly diagnosed multiple myeloma 6