Multiple myeloma

Myeloma is a clonal plasma-cell malignancy causing organ injury through marrow infiltration, bone destruction and monoclonal immunoglobulin or light chains. Suspect it with persistent bone or back pain, fracture, anaemia, renal impairment, hypercalcaemia, recurrent infection, high total protein, neuropathy or rouleaux. Some patients lack a visible serum M-spike, especially light-chain or non-secretory disease. Examine hydration, neurological function, skeletal tenderness, infection and amyloid features and seek emergencies before completing elective classification.

Order serum protein electrophoresis and serum free light chains together, with immunofixation if an abnormality is found. Add urine immunofixation or protein assessment when light-chain renal disease, AL amyloid or diagnosis requires it. Check FBC, film, calcium, phosphate, renal and liver function, albumin, LDH, beta-2 microglobulin and quantitative immunoglobulins. A broad gamma gap is not equivalent to monoclonality. Interpret free-light-chain ratio with renal function because polyclonal light chains rise in kidney disease, but marked clonal imbalance remains important.

Bone marrow aspirate and trephine confirm percentage and phenotype and supply enriched plasma-cell FISH, including high-risk lesions such as del(17p), t(4;14) and 1q gain or amplification under the accredited panel. Whole-body MRI is first-line imaging under NICE, with low-dose whole-body CT when unsuitable or declined. PET-CT is useful for extramedullary, non-secretory and response questions. A skeletal survey is a fallback, and isotope bone scan is inappropriate because myeloma suppresses osteoblast response.

Diagnose active disease when clonal marrow plasma cells are at least 10% or a plasmacytoma is present and at least one myeloma-defining event exists. CRAB thresholds include corrected calcium more than 0.25 mmol/L above upper normal or above 2.75 mmol/L, creatinine clearance below 40 mL/min or creatinine above 177 micromol/L, haemoglobin below 100 g/L or more than 20 g/L below normal, or at least one CT or radiographic lytic lesion. Injury must be attributable to the clone.

Biomarker-defined active disease prevents waiting for irreversible injury. SLiM criteria are at least 60% clonal marrow plasma cells, involved/uninvolved free-light-chain ratio at least 100 with involved light chain at least 100 mg/L, or more than one focal MRI lesion at least 5 mm. A patient below these thresholds without CRAB has smouldering myeloma or MGUS depending on clone size and is monitored. Solitary plasmacytoma requires whole-body and marrow assessment to exclude systemic disease.

Transplant-suitable adults receive a commissioned multi-drug induction, stem-cell collection, high-dose melphalan and autologous rescue, with consolidation and maintenance according to regimen and risk. NICE TA763 supports daratumumab plus bortezomib, thalidomide and dexamethasone around transplant. Melphalan 200 mg/m² IV is a common conditioning dose, reduced for renal, frailty or toxicity context. Transplant is not curative but deepens response; collect cells before prolonged marrow-toxic exposure.

Transplant-unsuitable care is frailty adapted. Current NICE options include daratumumab with lenalidomide and dexamethasone and, from 2026, daratumumab with bortezomib, lenalidomide and dexamethasone. Dose intensity must reflect cognition, falls, renal function, neuropathy, diabetes, cardiac reserve and support. Lenalidomide needs Cockcroft–Gault renal adjustment and thromboprophylaxis; bortezomib is preferably subcutaneous and weekly in frailty or neuropathy and is effective in renal failure. Dexamethasone should be reduced early when toxicity outweighs benefit.

Supportive treatment materially improves survival. Give zoledronic acid to eligible patients, including those without visible lesions under the myeloma protocol, after dental and renal assessment; use denosumab when indicated with calcium and vitamin D and a discontinuation plan. Provide aciclovir with proteasome inhibitors or anti-CD38 treatment, vaccination and prompt infection assessment. Choose aspirin or anticoagulant thromboprophylaxis during immunomodulatory treatment from VTE and bleeding risk. Avoid NSAIDs and contrast when renal injury is active, maintain hydration and treat pain and fractures through the multidisciplinary spine and orthopaedic service.

Monitor the marker that was measurable at diagnosis: SPEP, immunoglobulin, free light chain or urine where needed, plus FBC, renal and calcium at least every 3 months after recovery under NICE. Repeat marrow for response or unexplained cytopenia when it changes care, and image new pain, neurological symptoms, non-secretory disease or suspected extramedullary relapse. At each relapse review prior drug exposure and refractoriness, cytogenetic risk, duration of response, organ reserve, infection and patient goals before selecting the next antibody, proteasome, immunomodulatory or cellular platform.