From the Guidelines
The initial approach to treating a patient with amyloidosis involves first identifying the specific type of amyloidosis through comprehensive diagnostic testing, as treatment strategies differ significantly based on the amyloid protein involved. For AL amyloidosis, the most recent and highest quality study 1 suggests that treatment should be guided by ASCT-eligibility, with bortezomib-based regimens being a central role in upfront treatment, especially in the setting of high disease burden or foreseeable delay in ASCT.
Key Considerations
- The goal of therapy in AL amyloidosis is to achieve at least a hematological very good partial response (VGPR) with dFLC > 50 mg/L 1.
- Autologous stem cell transplantation (ASCT) may be considered for eligible patients, with bortezomib-based induction regimens being used in some cases 1.
- Supportive care is essential for all types of amyloidosis and includes managing organ-specific complications, such as diuretics for heart failure, dialysis for renal failure, and nutritional support.
- Treatment efficacy is monitored through regular assessment of organ function, biomarkers like serum free light chains for AL amyloidosis, and clinical response, with adjustments made as needed based on patient tolerance and disease progression.
Treatment Strategies
- For AL amyloidosis, bortezomib-based regimens, such as cyclophosphamide, bortezomib, and dexamethasone (CyBorD), are commonly used 1.
- For ATTR amyloidosis, tafamidis (20 mg daily) is often the first-line treatment for cardiac manifestations, while patisiran or inotersen may be used for hereditary ATTR with polyneuropathy.
- AA amyloidosis requires aggressive treatment of the underlying inflammatory condition.
Patient Assessment
- Patients should undergo comprehensive diagnostic testing, including history and physical examination, CBC, BUN, serum creatinine, and electrolytes, as well as immunofixation electrophoresis of both serum and urine to detect a monoclonal component 1.
- Genetic testing must be performed to identify the specific mutation in hereditary forms of amyloidosis, especially in African-Americans and patients with peripheral neuropathy 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 a patient presenting with amyloidosis is to use tafamidis to reduce cardiovascular mortality and cardiovascular-related hospitalization, as indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults 2.
- 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.
- Key considerations include monitoring for signs of BCRP substrate-related toxicities and modifying the dosage of the substrate if appropriate 2.
From the Research
Initial Approach to Treating Amyloidosis
The initial approach to treating a patient presenting with amyloidosis involves an accurate diagnosis and subtype classification, which are essential for disease prognostication and treatment 3.
Diagnosis and Treatment
- An accurate diagnosis of amyloidosis and its subtype classification are essential for disease prognostication and treatment 3.
- Current therapy for primary amyloidosis is suboptimal, but treatment with melphalan and prednisone may provide marginal survival benefit 3.
- A more aggressive approach such as autologous hematopoietic stem cell transplantation may offer potential for long-term benefit 3.
- New treatment modalities that were shown to have antitumor activity in multiple myeloma, such as high-dose dexamethasone and thalidomide, may also be of therapeutic value in primary amyloidosis 3.
- The combination of bortezomib and dexamethasone (BD) is feasible in patients with AL amyloidosis and can achieve a rapid hematologic response 4.
- BD regimen induced high rates of rapid hematologic and organ responses in AL amyloidosis patients 5.
Treatment Options
- Autologous hematopoietic stem cell transplantation may be considered for selected patients with AL amyloidosis 3, 6.
- Cyclophosphamide-bortezomib-dexamethasone, the anti-CD38 antibody daratumumab, and autologous stem cell transplant may be effective in treating AL amyloidosis 6.
- Bortezomib with dexamethasone as first-line treatment for AL amyloidosis with renal involvement may achieve high rates of hematologic and organ responses 5.