Treatment Approach for Multiple Myeloma
For patients with multiple myeloma, triplet therapy regimens should be used as the standard treatment, with specific regimens determined by transplant eligibility, risk stratification, and disease stage. 1
Initial Assessment and Risk Stratification
- All patients should undergo comprehensive staging including bone marrow examination with FISH for cytogenetic abnormalities, serum and urine protein electrophoresis, and whole-body low-dose CT scan (preferred over conventional skeletal survey) 1, 2
- Risk stratification is essential - high-risk features include del(17p), t(4;14), t(14;16), t(14;20) translocations, and early relapse post-transplant/initial therapy 3, 2
- Patient-specific factors including age, comorbidities, functional status, and frailty assessment should be evaluated to determine transplant eligibility 1, 4
Treatment for Transplant-Eligible Patients
- Induction therapy should consist of a triplet regimen including bortezomib, lenalidomide, and dexamethasone (VRd) 4, 5
- The most recent evidence shows that adding daratumumab to VRd (D-VRd) significantly improves progression-free survival (84.3% vs 67.7% at 48 months) and depth of response in transplant-eligible patients 6
- Following induction, patients should proceed to high-dose melphalan (200 mg/m²) with autologous stem cell transplantation (ASCT) 4, 7
- Consolidation therapy with the same regimen used for induction is recommended 7, 8
- Maintenance therapy with lenalidomide should be continued until disease progression 1
- For high-risk patients, consider bortezomib-based maintenance therapy 4, 2
Treatment for Transplant-Ineligible Patients
- Initial treatment should include at minimum a novel agent (immunomodulatory drug or proteasome inhibitor) and a steroid 1
- Preferred triplet regimens include:
- Initial dosing should be individualized based on patient age, renal function, comorbidities, functional status, and frailty status 1
- Continuous therapy is preferred over fixed-duration therapy when using immunomodulatory drug or proteasome inhibitor-based regimens 1
Treatment of Relapsed Disease
- Treatment of relapsed disease should be individualized based on prior treatment response, time to relapse, cytogenetic risk, and patient factors 1, 3
- All clinically relapsed patients with symptoms due to myeloma should be treated immediately 1, 3
- Triplet therapy should be administered on first relapse, though patient tolerance for increased toxicity should be considered 1
- Preferred regimens for first relapse include:
- Prior therapies should be considered when selecting treatment at relapse - use PI-based regimens for IMiD-refractory patients and IMiD-based regimens for PI-refractory patients 1, 3
- ASCT should be offered to transplant-eligible patients who did not receive it as part of initial therapy 1, 10
Special Considerations and Pitfalls
- Herpes zoster prophylaxis is recommended for patients treated with proteasome inhibitors 1
- Subcutaneous bortezomib is preferred for patients with pre-existing or high-risk peripheral neuropathy 1
- Full-dose aspirin or therapeutic anticoagulation is recommended for patients on immunomodulatory-based therapy 1
- Consider harvesting peripheral blood stem cells prior to prolonged exposure to lenalidomide 1
- There appears to be an increased risk for secondary cancers with lenalidomide maintenance following transplant - discuss risks and benefits with patients 1
- Exposure to myelotoxic agents should be limited to avoid compromising stem cell reserve in transplant-eligible patients 1
Response Assessment
- Depth of response should be assessed with each treatment cycle using serum and urine protein electrophoresis 1, 2
- Once best response is attained or on maintenance therapy, assessment may be less frequent but at minimum every 3 months 1, 2
- Complete response requires <5% plasma cells in bone marrow and negative immunofixation 2, 10