What is the treatment for amyloidosis?

Treatment for Amyloidosis

The treatment for amyloidosis depends on the specific type, with AL amyloidosis primarily treated with daratumumab-CyBorD (daratumumab with cyclophosphamide, bortezomib, and dexamethasone) as the preferred first-line therapy, while ATTR amyloidosis is treated with tafamidis. 1

Types of Amyloidosis and Their Treatments

AL Amyloidosis (Light-Chain Amyloidosis)

AL amyloidosis is the most common and severe form, caused by a plasma cell disorder that produces abnormal immunoglobulin light chains that deposit in tissues.

First-Line Treatment Options:

1. Daratumumab-CyBorD (preferred):

   • Combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone
   • Currently considered the emerging standard of care 1

2. Autologous Stem Cell Transplantation (ASCT):

   • Reserved for approximately 20% of patients who are eligible
   • Selection criteria: good performance status, limited cardiac involvement
   • May be used with or without bortezomib-based induction 1
   • Treatment-related mortality is approximately 3% in experienced centers 2

3. CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone):

   • Used when daratumumab is unavailable
   • Standard therapy for ASCT-ineligible patients 1

ATTR Amyloidosis (Transthyretin Amyloidosis)

ATTR amyloidosis is caused by misfolded transthyretin protein and primarily affects the heart.

Treatment:

• Tafamidis (Vyndaqel/Vyndamax): FDA-approved for ATTR cardiomyopathy to reduce cardiovascular mortality and hospitalization 3
• Important to differentiate from AL amyloidosis as management differs significantly 1

Treatment Algorithm Based on Amyloidosis Type

1. Confirm diagnosis and type:

   • Tissue biopsy with Congo red staining
   • Mass spectrometry for typing (gold standard)
   • Rule out other types of amyloidosis

2. For AL amyloidosis:

   • Assess ASCT eligibility:
     • If eligible: Consider ASCT with/without bortezomib-based induction
     • If ineligible: Proceed with Daratumumab-CyBorD (preferred) or CyBorD

3. For ATTR amyloidosis:

   • Tafamidis for cardiac involvement

Monitoring and Response Assessment

• Regular monitoring of hematologic response using free light chain assays
• Cardiac biomarkers (NT-proBNP, troponin) for cardiac involvement
• Renal function tests for kidney involvement
• Goal of therapy is to achieve very good partial response (VGPR) or better 4

Treatment of Relapsed/Refractory AL Amyloidosis

1. Daratumumab or daratumumab-based therapy is recommended for second-line treatment 1
2. For third-line treatment:
   • If relapse occurs ≥2 years after last therapy: Consider repeating original therapy
   • If not bortezomib-refractory: Bortezomib-based regimen
   • If bortezomib-refractory: Pomalidomide-dexamethasone or lenalidomide-dexamethasone 1

Important Considerations and Pitfalls

• Early diagnosis is critical: 25% of AL amyloidosis patients die within 6 months of diagnosis 5
• Cardiac toxicity: Monitor closely for cardiac complications, especially with proteasome inhibitors and immunomodulatory agents 1
• Renal toxicity: Lenalidomide can cause kidney dysfunction in 66% of patients 1
• Fluid retention: Corticosteroids can cause peripheral and pulmonary edema 1
• Multiorgan involvement: Over 69% of patients have more than one organ involved at diagnosis 1

Emerging Therapies

• Anti-CD38 antibodies (daratumumab) have shown promising results
• Targeted therapies for amyloid fibrils are under investigation 6
• Venetoclax shows promise for certain patients and needs further evaluation 6

Early recognition and prompt initiation of appropriate therapy before irreversible organ damage occurs remains the cornerstone of successful management in all types of amyloidosis.