Initial Treatment Approach for Multiple Myeloma
The initial treatment approach for multiple myeloma should be individualized based on transplant eligibility, with transplant-eligible patients receiving a triplet regimen containing a proteasome inhibitor and immunomodulatory drug followed by autologous stem cell transplantation, while transplant-ineligible patients should receive at minimum a novel agent and steroid, with triplet therapies like bortezomib-lenalidomide-dexamethasone or daratumumab-bortezomib-melphalan-prednisone preferred when tolerated. 1
Transplant-Eligible Patients (<65 years)
Induction Therapy
- For patients eligible for transplant, induction therapy should include a novel agent-based regimen to achieve the best depth of remission 1
- Bortezomib-based or lenalidomide-based triplet regimens are recommended as standard induction therapy 1
- Common regimens include:
- High-risk patients (with t(4;14), del(17p), or other high-risk cytogenetics) should preferentially receive a bortezomib-containing regimen 1
- Typically 4-6 cycles of induction therapy are administered before proceeding to transplant 1
Consolidation with Autologous Stem Cell Transplantation
- High-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation remains the standard of care for eligible patients 1
- Peripheral blood progenitor cells are preferred over bone marrow as the source of stem cells 1
- Double autologous transplantation may be considered for patients who do not achieve a very good partial remission after the first transplantation 1
Maintenance Therapy
- Continuous therapy is superior to fixed-duration therapy 1
- Lenalidomide maintenance has been shown to improve progression-free survival and overall survival following ASCT 1
- For high-risk patients, proteasome inhibitor-based maintenance (with or without lenalidomide) may be considered 1
Transplant-Ineligible Patients (>65 years or with comorbidities)
Initial Treatment
- Treatment should include at minimum a novel agent (immunomodulatory drug or proteasome inhibitor) plus a steroid 1
- Triplet therapies are preferred when tolerated and include:
- Dosing should be individualized based on patient age, renal function, comorbidities, functional status, and frailty status 1
- For very elderly or frail patients, dose modifications may be necessary (e.g., dexamethasone 20mg weekly for patients >75 years) 1
Maintenance Therapy
- Continuous therapy is recommended over fixed-duration therapy when initiating an immunomodulatory drug or proteasome inhibitor-based regimen 1
- Lenalidomide maintenance is recommended for patients who have completed initial therapy with a triplet regimen 1
Response Assessment and Monitoring
- Response should be assessed with each treatment cycle during active therapy 1
- Once best response is attained or on maintenance therapy, assessment should be done at minimum every 3 months 1
- Assessment includes:
- Whole-body low-dose CT scan is preferred over skeletal survey for bone surveillance 1
- MRD (minimal residual disease) assessment has prognostic value but should not guide treatment goals outside clinical trials 1
Special Considerations
- Renal dysfunction: Bortezomib-based regimens are preferred in patients with renal failure at presentation 1
- High-risk cytogenetics: Bortezomib-based regimens may overcome some adverse prognostic effects, especially in patients with t(4;14) translocation 1
- Elderly patients: Consider frailty assessment to guide treatment intensity and dose modifications 1
- Bisphosphonates: Long-term administration reduces skeletal events and should be proposed for patients with advanced disease 1
Common Pitfalls and Caveats
- Delaying treatment in asymptomatic (smoldering) myeloma: Immediate treatment is not recommended for patients with indolent myeloma unless they are part of a clinical trial 1, 4
- Undertreatment of elderly patients: Age alone should not exclude patients from effective therapies; functional status and comorbidities are more important determinants 1
- Inadequate response assessment: Regular monitoring is essential to determine treatment efficacy and make timely adjustments 1
- Neglecting supportive care: Management of bone disease, anemia, renal dysfunction, and infections is crucial alongside anti-myeloma therapy 1