From the Guidelines
Multiple myeloma is typically characterized by the classic pentad of hypercalcemia, renal failure, anemia, bone lesions, and recurrent infections (CRAB), and key diagnostic findings include monoclonal protein spike on serum protein electrophoresis, Bence Jones protein in urine, lytic bone lesions on skeletal survey, and bone marrow showing >10% clonal plasma cells, as noted in the most recent guidelines 1. The diagnosis of multiple myeloma requires a combination of clinical, laboratory, and radiologic findings. Patients often present with bone pain, pathologic fractures, or incidental findings of elevated protein or calcium on routine labs. Some key features of multiple myeloma include:
- Monoclonal protein spike on serum protein electrophoresis
- Bence Jones protein in urine
- Lytic bone lesions on skeletal survey described as "punched-out" lesions
- Bone marrow showing >10% clonal plasma cells
- Laboratory abnormalities such as elevated total protein with decreased albumin, hypercalcemia, elevated creatinine, normocytic anemia, and elevated ESR
- Rouleaux formation on peripheral blood smear is a classic finding The diagnostic criteria for multiple myeloma require either >60% plasma cells in bone marrow, serum free light chain ratio ≥100, or >1 focal lesion on MRI plus either >10% clonal plasma cells or biopsy-proven plasmacytoma, as outlined in the guidelines 1. It's also important to distinguish multiple myeloma from other plasma cell neoplasms, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, and to recognize complications like hyperviscosity syndrome and amyloidosis, as discussed in the guidelines 1. Remember that multiple myeloma is a disease of older adults, with a median age at diagnosis around 70 years, and the NCCN guidelines provide a framework for diagnosis and management 1.
From the Research
Key Presentations of Multiple Myeloma
- Multiple myeloma accounts for approximately 10% of hematologic malignancies 2, 3, 4
- The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) 2, 3, 4
- MDE include CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100, or >1 focal lesion on magnetic resonance imaging 2, 3, 4
Findings that Distinguish Multiple Myeloma
- The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma 2, 4
- The presence of any two high-risk factors is considered double-hit myeloma, and three or more high-risk factors is triple-hit myeloma 2, 4
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 5
Treatment and Management
- Standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone 5
- Induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients 5
- Patients who are not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression 4