From the Guidelines
Multiple myeloma is characterized by several key findings, including bone pain, anemia, elevated serum calcium, renal insufficiency, and increased total protein with a monoclonal spike on serum protein electrophoresis, as outlined in the International Myeloma Working Group (IMWG) diagnostic criteria 1. The diagnosis of multiple myeloma is based on the presence of clonal plasma cells in the bone marrow (≥10%) and one or more myeloma defining events (MDE), such as end-organ damage, high-risk cytogenetics, or a high serum involved to uninvolved free light chain (FLC) ratio 1. Some of the common findings in multiple myeloma include:
- Bone pain, particularly in the back or ribs, due to osteolytic lesions
- Anemia, elevated serum calcium, renal insufficiency, and increased total protein with a monoclonal spike on serum protein electrophoresis
- Urine tests showing Bence Jones proteinuria (free light chains)
- Radiographic findings, such as punched-out lytic bone lesions, osteoporosis, or pathologic fractures
- Bone marrow biopsy showing increased plasma cells (>10%, often >30%)
- Additional findings, such as hyperviscosity syndrome, recurrent infections due to immunodeficiency, and neurological symptoms from spinal cord compression or hypercalcemia The CRAB criteria (hypercalcemia, renal failure, anemia, bone lesions) are used for diagnosis, along with evidence of clonal plasma cells 1. Early recognition of these findings is crucial, as prompt treatment with combination chemotherapy regimens can significantly improve outcomes and quality of life for patients with multiple myeloma 1.
From the FDA Drug Label
14 CLINICAL STUDIES 14.1 Multiple Myeloma
A prospective, international, randomized (1:1), open-label clinical study (NCT00111319) of 682 patients was conducted to determine whether bortezomib administered intravenously (1. 3 mg/m2) in combination with melphalan (9 mg/m2) and prednisone (60 mg/m2) resulted in improvement in time to progression (TTP) when compared to melphalan (9 mg/m2) and prednisone (60 mg/m2) in patients with previously untreated multiple myeloma Efficacy results for the trial are presented in Table 10. At a prespecified interim analysis (with median follow-up of 16. 3 months), the combination of bortezomib, melphalan and prednisone therapy resulted in significantly superior results for time to progression, progression free survival, overall survival and response rate.
The findings of multiple myeloma in the study include:
- Time to Progression: The median time to progression was 20.7 months for the bortezomib, melphalan, and prednisone group, compared to 15 months for the melphalan and prednisone group.
- Progression-Free Survival: The median progression-free survival was 18.3 months for the bortezomib, melphalan, and prednisone group, compared to 14 months for the melphalan and prednisone group.
- Response Rate: The response rate (CR + PR) was 69% for the bortezomib, melphalan, and prednisone group, compared to 34% for the melphalan and prednisone group.
- Overall Survival: The median overall survival was 56.4 months for the bortezomib, melphalan, and prednisone group, compared to 43.1 months for the melphalan and prednisone group 2.
From the Research
Findings of Multiple Myeloma
The findings of multiple myeloma are as follows:
- Multiple myeloma is a hematologic malignancy characterized by the presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia 3.
- Approximately 73% of patients with multiple myeloma have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation 3.
- The Revised International Staging System combines data from serum biomarkers to assess estimated progression-free survival and overall survival 3.
- Standard first-line therapy consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, and is associated with median progression-free survival of 41 months 3.
- The addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival in patients with newly diagnosed myeloma 4.
- The combination of bortezomib, lenalidomide, and dexamethasone with panobinostat is safe and effective in patients with newly diagnosed multiple myeloma who are transplant eligible 5.
- Carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy is associated with high rates of minimal residual disease negativity in patients with newly diagnosed multiple myeloma 6.
Treatment Options
Some treatment options for multiple myeloma include:
- Bortezomib with lenalidomide and dexamethasone (VRd) 4
- Lenalidomide and dexamethasone alone (Rd) 4
- Bortezomib, lenalidomide, and dexamethasone with panobinostat 5
- Carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy 6
- Autologous stem cell transplant 3, 7
- Consolidation therapy and maintenance therapy 7
Patient Outcomes
Patient outcomes for multiple myeloma include:
- Median progression-free survival of 41 months with standard first-line therapy 3
- Median overall survival of 75 months with VRd therapy 4
- High rates of minimal residual disease negativity with carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy 6
- Improved progression-free and overall survival with the addition of bortezomib to lenalidomide and dexamethasone 4