Synopsis
Diagnose active myeloma using clonal plasma cells plus myeloma-defining events, separate it from precursor gammopathy and deliver fitness-, biology- and transplant-directed treatment with organ-protective support.
- Screen suspected myeloma with serum protein electrophoresis plus serum free light chains, then serum immunofixation; no single negative paraprotein test excludes non-secretory or light-chain disease.
- Confirm clonal plasma cells with marrow aspirate and trephine morphology and flow, and send plasma-cell FISH on enriched cells for prognosis.
- First-line skeletal imaging is whole-body MRI or whole-body low-dose CT; do not use isotope bone scanning because purely lytic disease may be missed.
- Active myeloma requires at least 10% clonal marrow plasma cells or plasmacytoma plus a myeloma-defining event attributable to the clone.
- CRAB events are hypercalcaemia, renal impairment, anaemia and one or more osteolytic lesions; exclude common competing causes before attribution.
- SLiM biomarkers are marrow clonal plasma cells at least 60%, involved-to-uninvolved free-light-chain ratio at least 100 with involved light chain at least 100 mg/L, or more than one MRI focal lesion at least 5 mm.
- Transplant suitability depends on physiological fitness, frailty, organ function and patient choice rather than age alone; induction is followed by stem-cell collection and high-dose melphalan autograft when suitable.
- NICE supports daratumumab plus bortezomib, thalidomide and dexamethasone for transplant-suitable adults and current daratumumab-based combinations for transplant-unsuitable adults.
- Give bone protection, infection prevention, antiviral prophylaxis with proteasome or anti-CD38 therapy and thromboprophylaxis with immunomodulatory drugs according to individual risk.
- Response uses M-protein and free light chains, marrow and imaging where indicated; biochemical change without symptoms can still represent relapse and requires the same trend method.
Key red flags
Severe back pain with weakness, sensory change or sphincter dysfunction is malignant spinal cord compression until urgent whole-spine MRI proves otherwise.
Oliguria, rising creatinine, hyperkalaemia or very high involved free light chain suggests cast nephropathy and requires immediate clone-directed therapy and removal of nephrotoxins.
Confusion, dehydration, arrhythmia, constipation or corrected calcium above 3.0 mmol/L requires emergency hypercalcaemia treatment and cardiac and renal monitoring.
Fever, rigors, hypotension or hypoxia may progress rapidly because myeloma impairs antibody function and treatment suppresses cellular immunity.
Rapid creatinine rise with high involved free light chain, bland urine or disproportionate protein pattern suggests cast nephropathy.
Thirst, polyuria, constipation, confusion, dehydration and arrhythmia accompany bone resorption and worsen renal light-chain clearance.
Investigation priorities
Detect intact monoclonal immunoglobulin and light-chain-only disease.
Identify lytic lesions, focal marrow disease, fracture and plasmacytoma.
Management branches
Bone pain, anaemia, renal impairment, hypercalcaemia, infection or paraprotein raises suspicion.
- Send FBC, calcium, renal, SPEP, immunofixation, free light chains, immunoglobulins and emergency-directed tests.
- Arrange marrow with flow and FISH and whole-body MRI or low-dose CT, escalating cord, renal or calcium emergencies immediately.
- Classify MGUS, smouldering, plasmacytoma or active myeloma using attributable CRAB and exact SLiM criteria.