What is the treatment approach for patients diagnosed with amyloidosis?

Treatment Approach for Amyloidosis

The treatment of amyloidosis must be tailored to the specific type, with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as the standard first-line therapy for AL amyloidosis, and tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily) as the first-line therapy for ATTR cardiac amyloidosis. 1

Accurate Diagnosis and Classification

Before initiating treatment, proper classification of amyloidosis is essential:

• AL amyloidosis: Requires tissue biopsy showing amyloid deposits and evidence of plasma cell dyscrasia
• ATTR amyloidosis: Requires bone scintigraphy and TTR gene sequencing to differentiate hereditary from wild-type 1

Treatment Algorithm by Amyloidosis Type

1. AL Amyloidosis Treatment

• First-line therapy: Daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD)

  • Based on the ANDROMEDA trial showing superior hematologic responses compared to CyBorD alone 1, 2
  • Goal is to achieve very good partial response (VGPR) after 4-6 cycles 3

• Special considerations:

  • For advanced cardiac involvement (NT-proBNP >8,500 pg/mL): Consider single-agent daratumumab with minimal dexamethasone 1
  • For pre-existing neuropathy: Avoid bortezomib or use attenuated dosing 1

• Autologous stem cell transplantation (ASCT):

  • Option for eligible patients (approximately 25% of newly diagnosed cases)
  • Target collection: at least 5 × 10^6 CD34+ cells/kg
  • G-CSF (10-16 μg/kg/day) without cyclophosphamide recommended for stem cell collection 1

2. ATTR Amyloidosis Treatment

• First-line therapy for cardiac ATTR amyloidosis:

  • Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily) - FDA-approved to reduce cardiovascular mortality and hospitalization 1, 4
  • Acoramidis (Attruby) - Novel TTR stabilizer that reduced all-cause mortality by up to 42% 1

• For ATTR polyneuropathy:

  • Patisiran - FDA-approved for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis 5

• Transplantation options:

  • Liver transplantation: Can cure the disease process in hereditary ATTR
  • Combined heart and liver transplantation: For selected patients with hereditary ATTR
  • Heart transplantation: For selected patients with advanced/stage D heart failure without significant extracardiac manifestations 1

Monitoring and Response Assessment

• Hematologic response: Assess within 3-6 months

  • Complete response: Absence of amyloidogenic light chains by SIFE and UIFE, normalized FLC ratio

• Organ response: Assess 6-12 months after hematologic response

  • Cardiac response: Decrease in NT-proBNP by >30% and <300 ng/L (if baseline >650 ng/L)

• Regular monitoring:

  • Monthly: CBC, basic biochemistry, NT-proBNP, troponin, serum-free light chain quantification
  • Every 6 months: Echocardiography with strain measurements and Holter ECG 1

Important Considerations and Pitfalls

• Early diagnosis is critical: 25% of patients with AL amyloidosis die within 6 months of diagnosis, and 25% of patients with ATTR amyloidosis die within 24 months 6

• Medication precautions:

  • Avoid digoxin and calcium channel blockers in patients with cardiac involvement
  • Use diuretics cautiously to prevent overdiuresis and volume contraction 1

• Anticoagulation: Warfarin (target INR 2-3) or direct oral anticoagulants recommended for atrial fibrillation in patients with cardiac involvement 1

• Palliative care: Should be integrated early for symptom management and quality of life improvement, especially for patients with advanced disease 7

• Multidisciplinary approach: Collaboration between hematologists, cardiologists, nephrologists, neurologists, and palliative care specialists is essential for optimal management 7, 1

By following this treatment algorithm based on amyloidosis type and organ involvement, clinicians can optimize outcomes and improve quality of life for patients with this complex disorder.