Multiple Myeloma Prognosis and Treatment
The prognosis for multiple myeloma varies significantly based on staging and risk factors, with median survival now approaching 5-7 years with modern therapies, though some patients may survive 10 years or longer even with conventional chemotherapy. 1, 2
Prognostic Factors
- The International Staging System (ISS) is a powerful three-stage classification based on serum β2-microglobulin and albumin levels, with ISS stage III associated with poorest outcomes 3
- Cytogenetic abnormalities detected by FISH are major prognostic factors, with t(4;14), deletion(17p), and t(14;16) associated with poorer outcomes 3
- The Revised International Staging System combines β2-microglobulin, albumin, and LDH with cytogenetic features to provide more accurate survival estimates - patients with stage I disease have a median 5-year survival of 82% 4
- Additional biological parameters with prognostic importance include C-reactive protein, LDH, and chromosome 1 abnormalities 3, 5
Diagnostic Criteria
- Diagnosis requires ≥10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma plus myeloma-defining events 3
- Myeloma-defining events include:
- Essential diagnostic tests include serum and urine protein electrophoresis with immunofixation, serum free light chain assay, bone marrow examination, and imaging studies 3, 7
Treatment Approach Based on Patient Characteristics
Smoldering (Asymptomatic) Myeloma
- Observation without immediate treatment is recommended 3, 6
- Regular monitoring every 3-6 months with laboratory tests 8
Symptomatic Myeloma in Elderly Patients (>65 years)
- Standard treatment has evolved from melphalan-prednisone to combination therapies 3
- Current regimens include melphalan-prednisone with thalidomide or other novel agents like bortezomib or lenalidomide 3
- Long-term bisphosphonate administration reduces skeletal events 3, 6
Symptomatic Myeloma in Younger Patients (<65 years)
- High-dose therapy with autologous stem cell transplantation (ASCT) is the standard treatment for eligible patients 3, 4
- Induction therapy typically includes a proteasome inhibitor (bortezomib), an immunomodulatory agent (lenalidomide), and dexamethasone 4
- Melphalan 200 mg/m² is the preferred preparative regimen before autologous transplantation 3
- Double ASCT may benefit some patients, though only one study shows overall survival benefit 3
Novel Therapies and Recent Advances
- Daratumumab (anti-CD38 monoclonal antibody) in combination with lenalidomide and dexamethasone has shown significant improvement in progression-free survival and overall survival in newly diagnosed patients ineligible for transplant 9
- Bispecific antibodies and CAR-T cell therapies are emerging as promising immunotherapy approaches 10
- The introduction of immunomodulatory drugs, monoclonal antibodies, and proteasome inhibitors has significantly improved remission duration and overall survival 10
Follow-Up and Monitoring
- Regular laboratory monitoring (every 3-6 months) including complete blood count, serum chemistry, quantitative immunoglobulins, serum protein electrophoresis, and free light chain assay 8
- Annual bone survey or as clinically indicated 8
- More frequent monitoring for progressive or relapsed disease 8
Common Pitfalls to Avoid
- Failure to obtain cytogenetic analysis, which provides crucial prognostic information 3, 6
- Missing early signs of disease progression by inadequate monitoring 8
- Not utilizing appropriate imaging to detect extramedullary disease 8
- Overlooking the potential for long-term survival even with conventional therapy in patients with favorable prognostic factors 2