What is the diagnosis and management of a patient with amyloidosis (a group of diseases characterized by abnormal protein deposits) experiencing recurrent falls?

From the Guidelines

Patients with amyloidosis experiencing recurrent falls should be managed with a multidisciplinary approach focusing on both the underlying disease and fall prevention, including the use of midodrine for orthostatic hypotension as recommended by the European Myeloma Network 1.

Key Considerations

• Treatment should include disease-specific therapy such as chemotherapy regimens (e.g., bortezomib, cyclophosphamide, and dexamethasone) for AL amyloidosis or TTR stabilizers for ATTR amyloidosis.
• Fall prevention requires physical therapy with balance training, assistive devices like canes or walkers, and home modifications including removal of tripping hazards and installation of grab bars.
• Orthostatic hypotension should be managed with compression stockings, adequate hydration, and medications like midodrine (2.5-10mg three times daily) or fludrocortisone (0.1-0.2mg daily) if needed, as suggested by the European Myeloma Network recommendations 1.
• Regular neurological and cardiac evaluations are essential as amyloid deposits in these systems contribute to fall risk through neuropathy, dysautonomia, and cardiac dysfunction.
• Medication review is crucial to minimize drugs that increase fall risk, particularly sedatives and antihypertensives.

Disease-Specific Therapy

• For AL amyloidosis, chemotherapy regimens such as bortezomib, cyclophosphamide, and dexamethasone can be effective, with considerations for autologous stem cell transplantation (ASCT) in eligible patients 1.
• For ATTR amyloidosis, TTR stabilizers like tafamidis may be used, although the provided evidence does not directly discuss its application in the context of falls.

Fall Prevention and Management

• The use of midodrine for orthostatic hypotension is specifically recommended by the European Myeloma Network 1, highlighting its importance in managing a common cause of falls in amyloidosis patients.
• A comprehensive approach addressing both the protein deposition disease and its manifestations that lead to falls is crucial for improving patient safety and quality of life.

Recent Guidelines and Recommendations

• The European Myeloma Network recommendations 1 and comprehensive reviews of AL amyloidosis 1 provide guidance on the management of amyloidosis, including the treatment of relapsed/refractory disease and the role of novel agents.
• These guidelines and reviews support the use of a multidisciplinary approach, including disease-specific therapy, fall prevention strategies, and management of orthostatic hypotension, to improve outcomes in patients with amyloidosis experiencing recurrent falls.

From the FDA Drug Label

INDICATIONS AND USAGE VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. (1) The answer to the question about amyloidosis with recurrent falls is not directly addressed in the provided drug label for tafamidis (PO) 2. The label only mentions the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis, without any reference to recurrent falls.

• The label does not provide information on the management of recurrent falls in patients with amyloidosis.
• No conclusion can be drawn about the use of tafamidis (PO) for amyloidosis with recurrent falls based on the provided label.

From the Research

Amyloidosis and Recurrent Falls

• There is no direct evidence in the provided studies that links amyloidosis with recurrent falls.
• However, some studies suggest that amyloidosis can cause organ dysfunction, including cardiac and renal problems, which may increase the risk of falls due to related symptoms such as dizziness or weakness 3, 4, 5.
• Treatment of AL amyloidosis with oral melphalan and dexamethasone has been shown to be effective in inducing hematologic remission and clinical improvement in some patients 3, 6.
• High-dose melphalan and autologous stem-cell transplantation has also been used to treat AL amyloidosis, with significant improvements in survival and organ response in selected patients 4.
• The use of molecularly targeted drugs against the plasma cell CD38 has begun to be explored as a treatment option for AL amyloidosis 5.
• Treatment with oral melphalan, dexamethasone, and thalidomide has been shown to be feasible and effective in patients with advanced cardiac AL amyloidosis 7.

Treatment Options

• Oral melphalan and dexamethasone is considered a standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation 6.
• High-dose melphalan and autologous stem-cell transplantation is a treatment option for selected patients with AL amyloidosis 4.
• Molecularly targeted drugs against the plasma cell CD38 are being explored as a treatment option for AL amyloidosis 5.
• Combination therapy with oral melphalan, dexamethasone, and thalidomide is a treatment option for patients with advanced cardiac AL amyloidosis 7.

Prognostic Factors

• Hematologic response rates and complete response rates are important prognostic factors in patients with AL amyloidosis 6.
• Use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy are independent prognostic determinants 6.