What is the recommended treatment for a patient with a final diagnosis of multiple myeloma based on lambda-restricted plasma cells in the bone marrow aspirate?

From the Guidelines

The recommended treatment for multiple myeloma with lambda-restricted plasma cells typically involves combination therapy, with a triplet regimen including a proteasome inhibitor, an immunomodulatory drug, and a corticosteroid, as outlined in the most recent guidelines 1.

Key Considerations

• Initial treatment usually consists of a triplet regimen including a proteasome inhibitor (bortezomib, carfilzomib), an immunomodulatory drug (lenalidomide, thalidomide), and a corticosteroid (dexamethasone) 1.
• For example, VRd (bortezomib 1.3 mg/m² subcutaneously days 1,8,15; lenalidomide 25 mg orally days 1-14; dexamethasone 40 mg orally days 1,8,15,22) given in 21-day cycles for approximately 4-6 cycles is a common regimen.
• For transplant-eligible patients under age 70-75 with good performance status, high-dose chemotherapy followed by autologous stem cell transplantation should be considered after initial therapy 1.
• Following transplant or primary therapy, maintenance therapy with lenalidomide (10-15 mg daily) is typically continued until disease progression.
• Treatment selection should be individualized based on patient factors including age, comorbidities, cytogenetic risk profile, and renal function.
• The lambda light chain restriction is a diagnostic feature but doesn't specifically alter the treatment approach compared to kappa-restricted myeloma.
• Regular monitoring of serum and urine protein electrophoresis, free light chains, complete blood counts, calcium, and renal function is essential to assess treatment response.

Important Factors to Consider

• Patient age and performance status
• Cytogenetic risk profile
• Renal function
• Presence of comorbidities
• Patient preferences and goals of care

Ongoing Care and Monitoring

• Regular assessment of response to treatment
• Monitoring for potential side effects and toxicities
• Adjustment of treatment plan as needed based on patient response and tolerability.

From the FDA Drug Label

The MAIA study demonstrated an improvement in Progression Free Survival (PFS) in the DRd arm as compared to the Rd arm; the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (hazard ratio [HR]=0.56; 95% CI: 0.43,0.73; p<0.0001), representing a 44% reduction in the risk of disease progression or death in patients treated with DRd. After a median follow-up of 56 months, MAIA demonstrated an improvement in overall survival (OS) in the DRd arm as compared to the Rd arm (HR=0.68; 95% CI: 0.53,0.86; p=0.0013), representing a 32% reduction in the risk of death in patients treated in the DRd arm.

The recommended treatment for a patient with a final diagnosis of multiple myeloma based on lambda-restricted plasma cells in the bone marrow aspirate is daratumumab in combination with lenalidomide and dexamethasone. This treatment regimen has been shown to improve progression-free survival and overall survival in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant, as demonstrated in the MAIA study 2.

• Key points:
  • Daratumumab in combination with lenalidomide and dexamethasone improves PFS and OS in patients with newly diagnosed multiple myeloma.
  • The median PFS was not reached in the DRd arm and was 31.9 months in the Rd arm.
  • The median OS was not reached for either arm, with a 32% reduction in the risk of death in patients treated in the DRd arm.
• Treatment regimen: Daratumumab 16 mg/kg in combination with lenalidomide and low-dose dexamethasone.

From the Research

Treatment Options for Multiple Myeloma

The presence of lambda-restricted plasma cells in the bone marrow aspirate is indicative of multiple myeloma. The recommended treatment for this condition depends on various factors, including the patient's age, overall health, and specific characteristics of the disease.

Transplant-Eligible Patients

• For transplant-eligible patients, the combination of daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) has shown promising results, with a higher stringent complete response rate compared to lenalidomide, bortezomib, and dexamethasone (RVd) alone 3.
• Another study found that lenalidomide, bortezomib, and dexamethasone (RVD) therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone 4.

Transplant-Ineligible Patients

• For transplant-ineligible patients, the combination of bortezomib-melphalan-prednisone (VMP) or lenalidomide-dexamethasone (Rd) followed by lenalidomide maintenance has been shown to be effective 5.
• The choice between VMP and Rd may depend on the patient's age and cytogenetic risk, with VMP being more effective in high-risk patients and Rd being more effective in older patients (>75 years) with standard-risk cytogenetics 5.

Refractory/Relapsed Multiple Myeloma

• For patients with refractory/relapsed multiple myeloma, the combination of elotuzumab with pomalidomide and dexamethasone has shown promising results, with improved progression-free and overall survival 6.
• This regimen may become a standard of care in the second line of therapy for patients who have received upfront treatment with a proteasome inhibitor and lenalidomide 6.