Treatment Options for Amyloidosis
Treatment for amyloidosis must be tailored to the specific type of amyloid protein involved, with daratumumab-based regimens recommended for AL amyloidosis and tafamidis for ATTR cardiomyopathy. 1
Accurate Diagnosis and Classification
Proper classification is essential before initiating treatment:
- AL amyloidosis: Caused by immunoglobulin light chain deposits
- ATTR amyloidosis: Caused by transthyretin protein deposits
- ATTRwt (wild-type)
- ATTRv (variant/hereditary)
Diagnostic workup should include:
- Tissue diagnosis (abdominal fat aspiration preferred initially)
- Immunohistochemistry
- Mass spectrometry (gold standard for typing)
- Cardiac biomarkers
- Genetic testing for hereditary forms 1
Treatment for AL Amyloidosis
First-Line Treatment Options
Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD)
- Recommended as first-line treatment by the American College of Cardiology
- Achieves high rates of deep hematologic responses 1
- Significantly increases the proportion of patients achieving hematologic complete response compared to CyBorD alone 2
- Improves cardiac and renal response rates at 6 and 12 months 2
CyBorD alone (cyclophosphamide, bortezomib, dexamethasone)
Alternative Regimens
Bortezomib, lenalidomide, and dexamethasone (VRD)
- Can induce deep hematologic responses (82% overall response rate)
- 32% complete response rate
- Higher toxicity profile compared to other regimens 4
High-dose melphalan with autologous stem cell transplantation (HDM/SCT)
- Option for eligible patients without significant cardiac involvement
- Treatment-related mortality of approximately 3%
- 70% achieve very good partial hematologic response or better
- Median survival >15 years in those achieving complete response 1
Treatment for ATTR Amyloidosis
FDA-Approved Treatment
- Tafamidis
- Only FDA-approved treatment for ATTR cardiomyopathy
- Recommended dosage: 80 mg VYNDAQEL or 61 mg VYNDAMAX
- Reduces cardiovascular mortality and hospitalization
- Well-tolerated with no significant side effects reported in clinical trials 1
Emerging Treatment
- Acoramidis
- Indicated for ATTR cardiac amyloidosis 1
Advanced Disease Options
Heart transplantation
- Considered for end-stage disease
- Often combined with liver transplantation for ATTRv
- 5-year survival rate of 50-80% 1
Liver transplantation
- Can cure the disease process as TTR protein is synthesized in the liver
- 5-year survival rate of 50-80% for combined heart and liver transplantation 1
Symptom Management
- Diuretics: Used judiciously as the mainstay of symptom management
- Anticoagulation: Indicated for atrial fibrillation, embolic stroke/TIA, or intracardiac thrombus
- Medications to use with caution or avoid: β-blockers, digoxin, calcium channel blockers, and ACE inhibitors/ARBs 1
Monitoring and Follow-up
Monthly monitoring should include:
- Complete blood count
- Biochemistry
- NT-proBNP
- Troponin
- Serum-free light chain quantification
Every 6 months:
- Echocardiography with strain measurements
- Holter ECG 1
Common Pitfalls and Caveats
Treatment without proper typing: Never initiate treatment without confirming the specific amyloid type, as treatments differ significantly between AL and ATTR amyloidosis.
Cardiac toxicities of treatment agents:
- Proteasome inhibitors: Heart failure (6.4%), LVEF reduction (23%)
- Immunomodulatory agents: Paradoxical increase in cardiac biomarkers
- Daratumumab: Cardiac failure (12%), arrhythmias (8%) 1
Treatment-related mortality: Particularly concerning in patients with advanced cardiac involvement 1
Medication interactions: Careful medication management is crucial due to potential adverse effects in amyloidosis patients 1
Response assessment: Monitoring for treatment response using serum free light chain assays is critical for managing AL amyloidosis 1