What is the treatment for amyloidosis?

Treatment for Amyloidosis

For amyloidosis treatment, daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) is the preferred first-line therapy for AL amyloidosis based on the most recent evidence, while tafamidis is indicated for ATTR amyloidosis. 1

Types of Amyloidosis and Their Specific Treatments

AL Amyloidosis (Light Chain)

AL amyloidosis results from the deposition of misfolded immunoglobulin light chains produced by abnormal plasma cells. Treatment focuses on targeting these abnormal plasma cells:

1. First-line therapy:

   • Daratumumab-CyBorD (daratumumab with cyclophosphamide, bortezomib, and dexamethasone) 1
     • Produces unprecedented high rates of deep hematologic responses
     • FDA-approved specifically for AL amyloidosis
     • Preferred regimen for newly diagnosed patients

2. For transplant-eligible patients:

   • High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 1
     • Eligibility criteria typically include:
       • Preserved organ function
       • LVEF >40%
       • Absence of advanced cardiac involvement
     • Only about 25% of newly diagnosed patients are eligible
     • May be preceded by Dara-CyBorD induction

3. For transplant-ineligible patients:

   • Dara-CyBorD (preferred) 1
   • CyBorD (cyclophosphamide, bortezomib, dexamethasone) 1, 2
   • Melphalan with dexamethasone for those who cannot tolerate other regimens 2

4. For patients with very advanced cardiac involvement:

   • Single-agent daratumumab with minimal dexamethasone 1

ATTR Amyloidosis (Transthyretin)

1. Wild-type or hereditary ATTR cardiomyopathy:

   • Tafamidis - FDA-approved to reduce cardiovascular mortality and hospitalization 3
   • Stabilizes TTR molecule to prevent misfolding and amyloid formation

2. For hereditary ATTR with advanced disease:

   • Consider combined heart and liver transplantation (5-year survival 50-80%) 1
   • Liver transplantation cures the underlying disease process as TTR is synthesized in the liver

Monitoring Treatment Response

Hematologic Response in AL Amyloidosis

• Complete response (CR): Absence of amyloidogenic light chains by SIFE and UIFE
• Very good partial response (VGPR): dFLC <40 mg/L
• Partial response (PR): dFLC decrease ≥50% 1

Organ Response Criteria

• Cardiac: Decrease in NT-proBNP by >30% and <300 ng/L
• Renal: At least 30% decrease in proteinuria or drop below 0.5 g/24h
• Hepatic: 50% decrease in abnormal alkaline phosphatase or decrease in liver size by ≥2 cm 1

Multidisciplinary Approach

1. Collaboration with cardiology is essential for:

   • Monitoring for cardiac decompensation during therapy
   • Managing heart failure symptoms
   • Assessing candidacy for heart transplantation 1

2. Collaboration with nephrology for patients with renal involvement

3. Involvement of geriatrics and palliative care to review goals of care 1

Important Caveats and Pitfalls

• Cardiac medications: Standard heart failure medications (calcium channel blockers, beta-blockers, ACE inhibitors) may be ineffective or harmful in amyloid heart disease; diuretics are the mainstay 4

• Digoxin: Should be avoided in amyloidosis patients as it binds to amyloid fibrils, increasing toxicity risk 1

• Anticoagulation: Consider in patients with atrial fibrillation, history of embolic events, or intracardiac thrombus 1

• Monitoring toxicity: Chemotherapy agents can cause cardiac toxicity; close monitoring is required 1

• Diagnostic pitfalls: Don't rely solely on SPEP/UPEP to exclude monoclonal proteins in suspected AL amyloidosis; use serum free light chains, SIFE, and UIFE for accurate diagnosis 1, 4

• Avoid NSAIDs and IV contrast in patients with renal impairment 1

By targeting the underlying pathological process and providing appropriate supportive care, treatment can improve organ function and survival in many patients with amyloidosis.