AL amyloidosis — Rapid | Doctor’s Passport

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.
Never infer AL solely from a monoclonal band: older patients may have both MGUS and transthyretin cardiac amyloid, which requires completely different therapy.
NICE-supported first-line treatment for newly diagnosed systemic AL is daratumumab plus bortezomib, cyclophosphamide and dexamethasone, individualised for cardiac stage, frailty and organ function.
Daratumumab 1,800 mg subcutaneously is given weekly for eight weeks, every two weeks through week 24, then every four weeks, stopping by 24 cycles under NICE TA959.
Supportive care is active treatment: cautious diuresis, salt review, blood-pressure protection, arrhythmia management, renal and nutritional care can determine whether clone therapy is tolerated.
ACE inhibitors, ARBs, beta blockers and vasodilators are often poorly tolerated in cardiac AL; use only for a clear indication with specialist titration rather than by routine heart-failure habit.
Assess haematological response with involved free light chain or dFLC and assess cardiac and renal response separately; organ improvement lags behind clone suppression.
Urgent specialist assessment is required for syncope, hypotension, arrhythmia, rapidly worsening oedema, acute kidney injury or major bleeding.

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.

Nephrotic proteinuria, falling eGFR or albumin with a monoclonal protein can represent renal AL despite a small marrow clone and normal calcium.

Macroglossia, periorbital purpura, bilateral carpal tunnel syndrome, autonomic neuropathy or unexplained bruising are high-value multisystem clues.

A monoclonal protein in suspected cardiac amyloid does not prove AL; obtain definitive fibril typing because transthyretin amyloid can coexist with MGUS.

Syncope, ventricular arrhythmia, severe postural hypotension or rapidly worsening congestion indicates high early mortality risk and needs same-day specialist review.

Investigation priorities

First-line: complete monoclonal screenFirst stepFirst line

Find a small plasma-cell clone with maximum non-invasive sensitivity.

Reference standard: proteomic fibril typingReference standard

Identify the deposited precursor protein and prevent inappropriate chemotherapy.

Management branches

Suspected systemic ALScreen clone and organs in parallel

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.
Refer early to the amyloidosis service for fibril typing, organ staging and a coordinated treatment decision.

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.Obtain group, screen and extended phenotype or genotype before daratumumab; screen hepatitis B, give required premedication and infection prophylaxis, and monitor reactions and cytopenia. Reduce partner intensity for advanced cardiac disease, frailty, neuropathy, hepatic or renal dysfunction. Apply cyclophosphamide reproductive counselling.

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.Assess baseline peripheral and autonomic neuropathy, blood pressure, platelet count and hepatic function. Hold and reduce for neuropathic pain or significant toxicity. Give antiviral prophylaxis against zoster. No routine starting reduction is required solely for renal failure, but coordinate administration around dialysis.

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