From the Guidelines
The initial approach to treating amyloidosis should focus on managing the underlying condition causing the protein buildup and addressing organ damage, with the most recent evidence suggesting that chemotherapy regimens such as bortezomib, cyclophosphamide, and dexamethasone (CyBorD), or daratumumab-based combinations are effective for AL amyloidosis 1.
Key Considerations
- The goal of treatment is to eradicate the pathological plasma cells and remove the affected light chain from the circulation, thereby limiting further organ damage and allowing for regression of tissue amyloid deposits 1.
- Early intervention is crucial as amyloidosis treatment aims to prevent further organ damage rather than reverse existing damage, which explains why prompt diagnosis and treatment initiation significantly impact prognosis and quality of life.
- For AL amyloidosis, first-line treatment usually involves chemotherapy regimens such as bortezomib (Velcade), cyclophosphamide, and dexamethasone (CyBorD), or daratumumab-based combinations to target the abnormal plasma cells producing the amyloid proteins 1.
- Supportive care is essential and includes diuretics for heart failure, blood pressure management, and nutritional support.
- In eligible patients with AL amyloidosis, autologous stem cell transplantation may be considered, although it is associated with significant toxicity and is typically reserved for a small proportion of patients 1.
Treatment Options
- Chemotherapy regimens such as bortezomib, cyclophosphamide, and dexamethasone (CyBorD) or daratumumab-based combinations for AL amyloidosis 1.
- Medications like tafamidis (Vyndaqel, 80mg daily) or patisiran (Onpattro, 0.3 mg/kg IV every 3 weeks) may be used to stabilize transthyretin proteins or reduce their production for ATTR amyloidosis.
- Autologous stem cell transplantation for eligible patients with AL amyloidosis 1.
Important Notes
- The treatment of AL amyloidosis is derived from anti–plasma-cell multiple myeloma therapies 1.
- Management of AL amyloidosis is complex and requires a multidisciplinary approach, including hematologists, cardiologists, and other specialists 1.
From the FDA Drug Label
VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. The initial approach to treating amyloidosis is with tafamidis, specifically for the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults.
- The recommended dosage is either VYNDAQEL 80 mg (four 20-mg tafamidis meglumine capsules) orally once daily or VYNDAMAX 61 mg (one 61-mg tafamidis capsule) orally once daily 2.
- Key considerations for treatment include reducing cardiovascular mortality and cardiovascular-related hospitalization. The treatment goal is to improve outcomes for patients with ATTR-CM. 2 2
From the Research
Initial Approach to Treating Amyloidosis
The initial approach to treating amyloidosis involves various chemotherapy regimens, depending on the type and severity of the disease.
- Bortezomib, lenalidomide, and dexamethasone (VRD) is a commonly used regimen for light-chain (AL) amyloidosis, as seen in a study published in 2019 3.
- Cyclophosphamide, bortezomib, and dexamethasone (CVD) is another effective regimen for AL amyloidosis, with high clonal response rates and prolonged progression-free survival 4.
- Bortezomib-based chemotherapies have also been shown to be effective in autologous stem cell transplantation-ineligible patients with AL amyloidosis, with a hematologic overall response rate of 65.1% 5.
- Bortezomib with dexamethasone (BD) as first-line treatment for AL amyloidosis with renal involvement has also been reported to induce high rates of rapid hematologic and organ responses 6.
Treatment Outcomes
The treatment outcomes for amyloidosis vary depending on the regimen used and the severity of the disease.
- A study published in 2019 reported a 12-month survival rate of 73% for patients treated with VRD 3.
- Another study published in 2012 reported an estimated 2-year progression-free survival rate of 66.5% for patients treated with CVD upfront 4.
- A study published in 2021 reported no significant difference in progression-free survival or overall survival according to regimen in autologous stem cell transplantation-ineligible patients with AL amyloidosis 5.
- A study published in 2016 reported a median duration of progression-free survival of 45 months and estimated overall survival rates at 12 and 24 months of 83% and 76%, respectively, for patients treated with BD 6.
Diagnostic Challenges
The diagnostic challenges of cardiac amyloidosis are significant, and delays in diagnosis can have detrimental consequences on patient outcomes 7.