What is the initial approach to treating amyloidosis (a condition characterized by the deposition of abnormal proteins in various tissues)?

Initial Approach to Treating Amyloidosis

The initial approach to treating amyloidosis must begin with accurate diagnosis and typing of the amyloid protein, as treatment strategies differ fundamentally between AL (light chain) and ATTR (transthyretin) amyloidosis—AL requires chemotherapy targeting the plasma cell clone, while ATTR-CM requires transthyretin stabilization. 1

Step 1: Establish Diagnosis and Type the Amyloid

For AL Amyloidosis

• Tissue biopsy with Congo red staining is mandatory to demonstrate amyloid deposits, which appear apple-green under polarized light 1, 2
• Abdominal fat pad aspiration is the preferred initial biopsy site with 84% sensitivity for AL-CM, being less invasive than organ biopsy 1
• If fat pad aspiration is negative but suspicion remains high, proceed to biopsy of the affected organ 1
• Mass spectrometry (LC-MS/MS) is the gold standard for typing with 88% sensitivity and 96% specificity—immunohistochemistry alone is insufficient 1, 2

Confirm Plasma Cell Dyscrasia

• Obtain serum free light chains (sFLC), serum immunofixation electrophoresis (SIFE), and urine immunofixation electrophoresis (UIFE) simultaneously 1
• Do not rely on SPEP/UPEP alone—these have lower sensitivity and will miss AL amyloidosis 1
• Perform bone marrow biopsy to demonstrate clonal proliferation of lambda or kappa-producing plasma cells 1, 3

Step 2: Assess Organ Involvement and Stage Disease

Cardiac Assessment (Most Critical for Prognosis)

• Cardiac involvement is the main driver of mortality in AL amyloidosis 3
• Staging is based on cardiac biomarkers (NT-proBNP, troponin) and guides treatment selection 4
• Restrictive cardiomyopathy is a key clinical clue for cardiac amyloidosis 1

Renal Assessment

• Two-thirds of AL patients present with renal involvement characterized by heavy proteinuria and nephrotic syndrome 5, 6
• Modified BMI (mBMI = serum albumin × BMI) <600 kg/m²·g/L indicates poor nutritional status and prognosis 1

Step 3: Initiate Type-Specific Treatment

For AL Amyloidosis

Daratumumab-CyBorD (daratumumab, cyclophosphamide, bortezomib, dexamethasone) is the current standard of care for both transplant-eligible and ineligible patients 3, 4

• The goal is to eradicate the pathological plasma cell clone producing amyloidogenic light chains 3, 4
• Deep hematologic response correlates with improved organ function and survival 3
• Autologous stem cell transplantation should be considered in eligible patients with low-risk status who do not achieve satisfactory response to daratumumab-based therapy 5, 4
• Monitor response with serial serum free light chain measurements 6

For ATTR-CM (Transthyretin Cardiac Amyloidosis)

Tafamidis is FDA-approved to reduce cardiovascular mortality and cardiovascular-related hospitalization 7

• Dosing: Either VYNDAQEL 80 mg (four 20-mg capsules) or VYNDAMAX 61 mg (one capsule) orally once daily 7
• These formulations are not substitutable on a per mg basis 7
• Capsules must be swallowed whole, not crushed or cut 7

Step 4: Provide Organ-Specific Supportive Care

Cardiac Management

• Avoid standard heart failure medications (calcium channel blockers, β-blockers, ACE inhibitors)—these are inefficient or dangerous in amyloid heart disease 6
• Use diuretics as the primary management for volume overload 6
• Consider amiodarone and pacemaker implantation for rhythm or conduction abnormalities 6

Gastrointestinal Symptoms

• Endoscopy with random biopsies (especially duodenum) using Congo red staining can confirm GI involvement 1
• Management is primarily supportive, as symptoms may result from autonomic neuropathy, cardiac congestion, or medication side effects 1

Critical Pitfalls to Avoid

• Do not assume facial droop is stroke—consider soft tissue infiltration, especially with macroglossia or periorbital purpura (pathognomonic for AL) 1, 3
• Do not skip amyloid typing—over 10% of patients with monoclonal gammopathy can have ATTR deposits, making typing essential 1
• Do not delay referral to specialized centers—adequate technology and expertise are required for proper workup and treatment 4
• Do not use standard heart failure medications in cardiac amyloidosis—they can be dangerous 6