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 of amyloidosis, with daratumumab-CyBorD being the current standard of care for AL amyloidosis and tafamidis for ATTR cardiac amyloidosis. 1

Diagnosis and Classification

Before initiating treatment, proper classification of amyloidosis is essential:

• AL amyloidosis: Requires both tissue biopsy showing amyloid deposits and evidence of plasma cell dyscrasia 2

  • Diagnostic workup: Serum free light chains, serum/urine immunofixation, bone marrow biopsy
  • Tissue biopsy: Abdominal fat aspiration (84% sensitivity for AL-CM) or affected organ biopsy

• ATTR amyloidosis: Can be diagnosed without tissue biopsy using bone scintigraphy for cardiac involvement 2

  • Requires exclusion of AL amyloidosis first
  • TTR gene sequencing to differentiate hereditary from wild-type

Treatment by Amyloidosis Type

AL Amyloidosis Treatment

1. First-line therapy:

   • Daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 1, 3
   • Produces very good partial responses or better in 78.5% of patients (vs. 49.2% with CyBorD alone) 1
   • Only FDA-approved agent specifically for AL amyloidosis 1

2. Alternative regimens:

   • CyBorD alone if daratumumab cannot be used 1
   • Bortezomib-melphalan-dexamethasone (BMD) 1

3. For eligible patients (approximately 25% of newly diagnosed cases):

   • High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 2, 1
   • Offers possibility of long-lasting remission with 70% achieving very good partial response or better 1
   • Median survival >15 years in complete responders 1
   • Treatment-related mortality ~3% in experienced centers 2

4. For patients with advanced cardiac involvement:

   • Single-agent daratumumab with minimal dexamethasone to reduce cardiotoxicity 1

ATTR Amyloidosis Treatment

1. First-line therapy:

   • Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily) 1, 4
   • Reduces cardiovascular mortality and cardiovascular-related hospitalization 4

2. Alternative therapy:

   • Acoramidis (Attruby) - a novel TTR stabilizer that reduced all-cause mortality by up to 42% 1

Special Considerations

Cardiac Involvement

• Cardiac involvement is a major determinant of risk and treatment eligibility 2

• Avoid medications that can cause toxicity in amyloidosis patients:

  • Digoxin and calcium channel blockers should be avoided 1
  • Diuretics should be used cautiously to prevent overdiuresis 1

• For atrial fibrillation:

  • Anticoagulation with warfarin (target INR 2-3) or direct oral anticoagulants 1

IgM-Associated Amyloidosis

• Rare condition with distinctive clinical characteristics 2
• Treatment should aim at rapid elimination of amyloidogenic light chains 2
• Monitor free light chains and cardiac biomarkers 2
• Bortezomib-based therapy can be used in carefully selected patients 2
• In selected patients, autologous stem cell transplantation may be considered 2

Monitoring and Response Assessment

• Hematologic response: Usually observed within 3-6 months of treatment initiation 1
• Organ response: Generally observed 6-12 months after hematologic response 1
• Monthly monitoring during initial treatment:
  • Complete blood count
  • Basic biochemistry
  • NT-proBNP and troponin
  • Serum-free light chain quantification for AL amyloidosis 1
• Every 6 months:
  • Echocardiography with strain measurements
  • Holter ECG 1

Treatment Challenges and Pitfalls

• Delayed diagnosis is common - 25% of AL amyloidosis patients die within 6 months of diagnosis 5
• Treatment is ineffective if end-organ damage is severe 5
• Cardiac involvement significantly impacts treatment options and survival 2
• Renal response after treatment is associated with improved survival 6
• Transient worsening of cardiac biomarkers may occur during initial treatment 1

Advanced Options

• Heart transplantation may be considered for selected patients with advanced/stage D heart failure 1
• Combined heart and liver transplantation may be considered for selected patients with hereditary ATTR 1

The key to successful management of amyloidosis is early diagnosis, proper typing, and prompt initiation of appropriate therapy before significant organ damage occurs.