What is the treatment for cardiac manifestations in Amyloid Light-chain (AL) amyloidosis?

From the Guidelines

The treatment of cardiac manifestations in AL amyloidosis should focus on two parallel approaches: treating the underlying plasma cell dyscrasia with a combination of bortezomib, cyclophosphamide, and dexamethasone, and managing the cardiac symptoms with diuretics, careful titration, and avoidance of certain medications that may exacerbate hypotension or negative inotropic effects, as recommended by the 2023 ACC expert consensus decision pathway 1.

Treatment of Underlying Plasma Cell Dyscrasia

• The standard therapy includes a combination of bortezomib, cyclophosphamide, and dexamethasone (CyBorD regimen) 1.
• Autologous stem cell transplantation may be considered for eligible patients, with a treatment-related mortality of approximately 3% and a median survival of over 15 years in those achieving a complete response 1.

Management of Cardiac Symptoms

• Diuretics, such as furosemide, are the cornerstone of therapy for fluid overload, with careful titration essential to avoid hypotension 1.
• Beta-blockers and ACE inhibitors should be used cautiously or avoided due to the risk of hypotension in amyloidosis patients 1.
• Calcium channel blockers are contraindicated due to their negative inotropic effects, and digoxin should be avoided due to increased binding to amyloid fibrils, raising toxicity risk 1.
• Anticoagulation with direct oral anticoagulants or warfarin is recommended for patients with atrial fibrillation due to high thromboembolism risk 1.

Considerations for Specific Patient Populations

• Heart transplantation followed by chemotherapy or stem cell transplantation may be considered in highly selected younger patients with isolated cardiac involvement 1.
• Prompt diagnosis and early treatment are crucial as cardiac amyloidosis carries a poor prognosis if left untreated 1.

From the Research

Treatment Options for Cardiac Manifestations in AL Amyloidosis

• The treatment of cardiac manifestations in AL amyloidosis involves various regimens, including cyclophosphamide, bortezomib, and dexamethasone (CVD) 2, as well as cyclophosphamide, bortezomib, and methylprednisolone (CyBorMe) 3.
• These regimens have shown high clonal response rates and prolonged progression-free survival in patients with AL amyloidosis, including those with cardiac involvement 2, 3.
• Bortezomib-based therapy has been found to be effective in treating cardiac AL amyloidosis, with improved outcomes when combined with daratumumab 4.
• Autologous stem cell transplant (ASCT) and heart transplant are also considered as treatment options for selected patients with AL-CA 4.

Efficacy of Treatment Regimens

• The CVD regimen has been associated with an overall hematologic response rate of 81.4%, including complete response (CR) in 41.9% and very good partial response with >90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4% 2.
• The CyBorMe regimen has been found to be efficacious and well-tolerated in patients with AL amyloidosis, with a hematological response rate of 92.8% 3.
• Bortezomib, cyclophosphamide, and dexamethasone have been found to be effective in treating cardiac AL amyloidosis, with meaningful responses in late-stage disease 5.

Future Directions

• Further research is needed to determine the optimal treatment approach for AL-CA, including the use of AI-driven algorithms for early diagnosis and treatment, as well as the development of newer genetic engineering technologies 6, 4.
• Well-designed, randomized controlled trials are necessary to provide evidence about the efficacy of different treatment regimens, including ASCT and heart transplant 4.