Synopsis
Recognise multisystem light-chain amyloid early, prove and type the deposits, stage cardiac risk and deliver rapid clone-directed therapy with organ-specific supportive care.
- AL amyloidosis is a plasma-cell disorder in which misfolded monoclonal light chains deposit as amyloid and damage organs; a small clone can cause lethal disease.
- Think AL in otherwise unexplained HFpEF or ventricular thickening, nephrotic proteinuria, peripheral or autonomic neuropathy, macroglossia, periorbital purpura, hepatomegaly or multisystem disease.
- Diagnosis requires Congo-red-positive tissue and definitive amyloid typing; laser microdissection with mass spectrometry is the reference standard when available.
Key red flags
Heart failure with preserved or mildly reduced ejection fraction, increased ventricular wall thickness, low-voltage ECG, hypotension or unexplained troponin elevation requires urgent amyloid evaluation.
Investigation priorities
Find a small plasma-cell clone with maximum non-invasive sensitivity.
Identify the deposited precursor protein and prevent inappropriate chemotherapy.
Management branches
Cardiac, renal, neurological, soft-tissue or multisystem clues suggest amyloid.
- Send serum electrophoresis, serum and urine immunofixation, free light chains and comprehensive cardiac, renal and liver baseline tests.
- Arrange fat and marrow sampling or affected-organ biopsy without allowing a small or absent M-spike to delay investigation.
Key medicines
Daratumumab plus VCdNICE-supported initial therapy uses 28-day cycles. Give daratumumab 1,800 mg subcutaneously weekly in cycles 1–2, every two weeks in cycles 3–6, then every four weeks; stop by 24 cycles. Give exact centre-protocol bortezomib, cyclophosphamide and dexamethasone for six cycles.
BortezomibA commonly used AL schedule is 1.3 mg/m² subcutaneously on days 1, 8, 15 and 22 of each 28-day cycle for six cycles within VCd; use the authorised amyloid centre protocol for timing and dose modifications.