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 consideration of patient factors such as age, comorbidities, cytogenetic risk, and renal function. When considering the treatment of multiple myeloma, it is essential to prioritize regimens that have demonstrated improved response rates and manageable adverse effects.

Key Considerations

• For standard-risk patients, lenalidomide or bortezomib in combination with dexamethasone are suitable options, with the choice depending on factors such as convenience of administration and plans for future treatment, as noted in 1.
• Bortezomib-based regimens are recommended for patients with renal failure at presentation due to their non-renal clearance, as highlighted in 1.
• The European Myeloma Network recommends novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients, with a triple combination of bortezomib, and either adriamycin or thalidomide and dexamethasone, or with cyclophosphamide and dexamethasone, as stated in 1.
• Maintenance therapy with thalidomide or lenalidomide can increase progression-free survival and possibly overall survival, as noted in 1.

Treatment Selection

• Treatment selection should be based on patient factors, including age, comorbidities, cytogenetic risk, and renal function.
• Supportive care, including bisphosphonates, prophylactic antivirals, and thromboprophylaxis, is essential to prevent complications and improve quality of life.
• The most recent and highest quality study, 1, provides guidance on the evaluation and treatment of newly diagnosed patients with multiple myeloma, emphasizing the importance of risk stratification and novel-agent-based induction therapy.

Key Regimens

• VRd (bortezomib, lenalidomide, dexamethasone) or KRd (carfilzomib, lenalidomide, dexamethasone) for transplant-eligible patients.
• VRd-lite (lower doses), Rd (lenalidomide, dexamethasone), or VMP (bortezomib, melphalan, prednisone) for transplant-ineligible patients.
• Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide as standards of care for transplant-ineligible patients, as recommended in 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 plus dexamethasone as a reference treatment for patients with newly diagnosed myeloma 3
• The combination of bortezomib with lenalidomide and dexamethasone (VRd) has shown significant efficacy in the setting of newly diagnosed myeloma 3, 4
• The addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival 3
• Carfilzomib, lenalidomide, and dexamethasone (KRd) is also a viable option for maintenance therapy after autologous stem-cell transplantation 5
• Isatuximab plus VRd has been shown to be more effective than VRd alone as initial therapy in patients with newly diagnosed multiple myeloma who are ineligible to undergo transplantation 6

Treatment Regimens

Some common treatment regimens for multiple myeloma include:

• VRd (bortezomib, lenalidomide, and dexamethasone) 3, 4, 6
• KRd (carfilzomib, lenalidomide, and dexamethasone) 5
• Isatuximab-VRd (isatuximab, bortezomib, lenalidomide, and dexamethasone) 6
• Daratumumab-based regimens (e.g. dara-Vd, dara-Kd, dara-Pd) 7

Efficacy and Safety

The efficacy and safety of these treatment regimens have been evaluated in various studies, including:

• The SWOG S0777 trial, which demonstrated the efficacy of VRd in patients with newly diagnosed myeloma 3
• The ATLAS trial, which compared the efficacy of KRd and lenalidomide alone as maintenance therapy after autologous stem-cell transplantation 5
• A real-world analysis of daratumumab-based regimens in relapsed/refractory multiple myeloma 7
• The IMROZ trial, which demonstrated the efficacy of isatuximab-VRd as initial therapy in patients with newly diagnosed multiple myeloma who are ineligible to undergo transplantation 6