What is the treatment for cardiac amyloidosis (Amyloidosis, a condition characterized by the deposition of amyloid, a protein, in the heart)?

From the Guidelines

Treatment for cardiac amyloidosis, specifically light chain (AL) amyloidosis, should prioritize daratumumab-CyBorD as the standard of care for newly diagnosed patients, given its unprecedented high rate of deep hematologic responses and approval by the FDA and European Medicines Agency 1. The goal of therapy in cardiac amyloidosis is to manage symptoms and slow disease progression, with approaches varying based on the specific type of amyloidosis. For AL amyloidosis, chemotherapy regimens such as bortezomib, cyclophosphamide, and dexamethasone are used to target the abnormal plasma cells producing the amyloid proteins, with autologous stem cell transplantation considered for eligible patients.

• Key considerations in treatment include:
  • The use of daratumumab-CyBorD as the preferred induction therapy before high-dose melphalan and stem cell transplantation (HDM/SCT) for eligible patients 1
  • The incorporation of daratumumab into bortezomib-based regimens for patients who are not candidates for SCT 1
  • The importance of early diagnosis and treatment to prevent further amyloid deposition and preserve cardiac function 1
  • The need for supportive care, including diuretics, careful use of beta-blockers and ACE inhibitors, and anticoagulation for patients with atrial fibrillation 1
• Lifestyle modifications, such as dietary sodium restriction and fluid management, are also crucial in managing cardiac amyloidosis. The most recent and highest quality study, the 2023 ACC expert consensus decision pathway, provides guidance on comprehensive multidisciplinary care for patients with cardiac amyloidosis, emphasizing the importance of a tailored approach to treatment 1.

From the FDA Drug Label

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. VYNDAQEL and VYNDAMAX are prescription medicines used to treat adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.

The treatment for cardiac amyloidosis (specifically transthyretin-mediated amyloidosis) is tafamidis (VYNDAQEL or VYNDAMAX) to reduce cardiovascular mortality and cardiovascular-related hospitalization 2, 2, 2.

• Key benefits: Reduce death and hospitalization related to heart problems.
• Target population: Adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM).

From the Research

Treatment Options for Cardiac Amyloidosis

• The mainstay of treatment for immunoglobulin light chain (AL)-mediated cardiac amyloidosis (AL-CA) is proteasome inhibitor-based chemotherapy with daratumumab and, when feasible, autologous stem cell transplantation 3.
• For transthyretin cardiac amyloidosis (ATTR-CA), the stabilizer tafamidis is the only US Food and Drug Administration (FDA)-approved treatment 3.
• Promising novel therapies on the horizon target various points in the ATTR-CA amyloidogenic cascade, including transthyretin gene (TTR) silencing agents, TTR tetramer stabilization, and inhibition of oligomer aggregation 3.
• Advanced interventions, such as heart, heart-kidney, and heart-liver transplantation, may be considered for end-stage cardiac amyloidosis 3, 4, 5.

Systemic Review of Treatment Strategies

• A systematic review of treatment strategies for AL-CA found that bortezomib-based therapy followed by high-dose melphalan and autologous stem cell transplant is a commonly used first-line treatment, with improved outcomes with the addition of daratumumab 6.
• The review also found that heart transplant can extend survival for selected patients who are not eligible for autologous stem cell transplant, but may affect tolerance of further chemotherapy 6.

Current Treatment and Future Directions

• Current treatment options for cardiac amyloidosis include specific treatment of amyloidosis and supportive treatment for cardiac-related symptoms, with the mainstay of supportive treatment being diuretic therapy 4.
• New therapies based on chemical and immunologic reaction with amyloid or its precursor are under intensive development, including CRISPR-Cas9-based drugs and monoclonal antibodies targeting misfolded ATTR or AL 7.
• Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations, followed by high-dose melphalan and autologous stem cell transplant in eligible patients, and heart transplant for selected severe cases 6, 5.