Multiple Myeloma Diagnosis and Treatment
The diagnosis of multiple myeloma requires ≥10% clonal plasma cells in bone marrow or a biopsy-proven plasmacytoma, plus evidence of organ damage attributable to the plasma cell disorder (CRAB criteria), or other myeloma-defining events as established by the International Myeloma Society. 1
Diagnostic Criteria and Workup
Required Diagnostic Tests
Blood Tests:
- Complete blood count with differential
- Blood chemistry: serum calcium, creatinine, albumin, beta-2 microglobulin, LDH 1
- Monoclonal component evaluation:
- Serum protein electrophoresis (SPEP)
- Serum immunofixation (IFE)
- Quantification of immunoglobulins (IgG, IgA, IgM)
- Serum free light chains with kappa/lambda ratio 1
Urine Tests:
- 24-hour urine collection for total protein
- Urine protein electrophoresis (UPEP)
- Urine immunofixation (UIFE) 1
Bone Marrow Assessment:
- Unilateral bone marrow aspirate and/or biopsy (diagnosis confirmed with >10% clonal plasma cells)
- CD138 staining for plasma cell percentage
- Flow cytometry (even if conventional morphology shows <10% plasma cells) 1
- Cytogenetic testing:
Imaging Studies:
Disease Classification
- Multiple Myeloma: ≥10% clonal plasma cells in bone marrow or plasmacytoma plus CRAB criteria or other myeloma-defining events 1, 2
- Smoldering Multiple Myeloma: Serum M-protein ≥3 g/dL and/or ≥10% clonal plasma cells, no CRAB criteria 1
- Monoclonal Gammopathy of Undetermined Significance (MGUS): <3 g/dL serum M-protein, <10% clonal plasma cells, no end-organ damage 1
- Solitary Plasmacytoma: Single lesion of monoclonal plasma cells, normal bone marrow, no other lesions on skeletal survey 1
Risk Stratification
- International Staging System (ISS) combines beta-2 microglobulin, albumin, LDH, and cytogenetic abnormalities 1
- High-risk features include del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation 2
- Double-hit myeloma: Presence of any two high-risk factors
- Triple-hit myeloma: Three or more high-risk factors 2
Treatment Approaches
Transplant-Eligible Patients
- Induction therapy: Anti-CD38 monoclonal antibody plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT) 2
- High-risk patients: Consider daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) 3
- Selected standard-risk patients can collect stem cells and delay transplant until first relapse 2
Transplant-Ineligible Patients
- Standard approach: VRd for approximately 8-12 cycles followed by maintenance 2
- Alternative approach: Daratumumab, lenalidomide, dexamethasone (DRd) until progression 4, 2
- DRd has shown significant improvement in progression-free survival (61.9 months vs. 34.4 months) and overall survival (32% reduction in risk of death) compared to Rd alone 4
Maintenance Therapy
- Standard-risk patients: Lenalidomide maintenance 1, 2
- High-risk patients: Bortezomib plus lenalidomide maintenance 1, 3, 2
Relapsed Disease
- Triplet regimens are usually needed at relapse
- Treatment choice varies with each successive relapse 2
- Newer options include CAR-T cell therapy and bispecific antibodies 2
Supportive Care
- Bisphosphonates to reduce skeletal-related events 1
- Radiation therapy for painful bone lesions or impending fractures 1
- Thromboprophylaxis and prophylaxis against infection 5
Monitoring and Follow-up
- Regular monitoring of serum and urine M-protein levels 1
- Assessment of minimal residual disease (MRD) in patients achieving complete response 1
- Periodic imaging to evaluate bone disease response 1
- Regular evaluation for treatment-related toxicities 1
Special Considerations
- Smoldering multiple myeloma requires close observation without immediate treatment, with monitoring every 3-4 months 1
- Solitary plasmacytoma should be treated with radiation therapy to the involved site, with close follow-up 1
- Early detection of disease progression through regular monitoring of free light chains can lead to more timely intervention 1