What are the treatment approaches for different types of amyloidosis?

Treatment Approaches for Different Types of Amyloidosis

For optimal patient outcomes, treatment of amyloidosis must be tailored to the specific amyloid type, with AL amyloidosis primarily treated with plasma cell-directed therapies, ATTR amyloidosis managed with specific stabilizers or silencers, and AA amyloidosis addressed by treating the underlying inflammatory condition. 1

Light Chain (AL) Amyloidosis Treatment

First-line Treatment Options

• Daratumumab-CyBorD (cyclophosphamide, bortezomib, and dexamethasone) is the preferred first-line therapy for most patients with AL amyloidosis based on recent FDA approval 2, 1
• High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) should be considered for eligible patients, offering possibility of long-lasting remission 2, 1
• Patient eligibility for transplant is determined by risk assessment, with cardiac involvement being a major determinant of risk 2

Treatment Selection Algorithm

• Assess transplant eligibility based on cardiac function, performance status, and extent of organ involvement 1
• For transplant-eligible patients: Consider HDM/SCT or Daratumumab-CyBorD 2, 1
• For transplant-ineligible patients: Daratumumab-CyBorD is the preferred option 1
• Alternative regimen: CyBorD without daratumumab for patients who cannot tolerate daratumumab 2

Medication Considerations and Toxicities

• Daratumumab (anti-CD38 antibody): Monitor for cardiac failure (12%), arrhythmias (8%), and atrial fibrillation (6%) 2, 1
• Proteasome inhibitors (bortezomib, carfilzomib, ixazomib): Watch for heart failure, decreased LVEF, and pulmonary hypertension 2
• Immunomodulatory agents (lenalidomide, pomalidomide): Be aware of paradoxical increases in cardiac biomarkers and kidney dysfunction 2
• Corticosteroids: Monitor for fluid retention, peripheral edema, and pulmonary edema 2

Transthyretin (ATTR) Amyloidosis Treatment

Treatment Options

• Tafamidis is recommended for TTR cardiac amyloidosis to stabilize transthyretin protein 1
• RNA-interference agents (patisiran, inotersen) are effective options for hereditary ATTR with polyneuropathy 3
• Liver transplantation may be considered for familial amyloidotic polyneuropathy 4

Management Approach

• Differentiate between wild-type (age-related) and variant (hereditary) ATTR as management strategies differ 1
• Provide supportive care for organ-specific complications, including careful fluid balance for heart failure 1
• Consider heart transplantation in select patients without significant extracardiac involvement 1

AA (Secondary) Amyloidosis Treatment

Primary Approach

• Treatment focuses on controlling the underlying chronic inflammatory condition 1, 5
• Monitor serum amyloid A (SAA) protein and CRP as markers of inflammation and disease activity 1
• High-flux hemodialysis may prevent dialysis-related amyloidosis 4

Diagnostic Considerations

Critical Diagnostic Steps

• Accurate diagnosis requires tissue biopsy with Congo Red staining showing characteristic apple-green birefringence under polarized light 1, 5
• Typing of amyloid protein is essential using mass spectrometry (gold standard), immunohistochemistry, or immunofluorescence 1
• Comprehensive monoclonal protein screening requires serum free light chain assay, serum immunofixation electrophoresis, and urine immunofixation electrophoresis 1

Common Pitfalls to Avoid

• Misdiagnosis between AL and ATTR amyloidosis can lead to inappropriate treatment 1, 3
• Delayed diagnosis significantly impacts survival, with 25% of AL amyloidosis patients dying within 6 months of diagnosis 6
• Patients with AL amyloidosis have higher risk for treatment-related toxicity than those with multiple myeloma 1
• Standard protein electrophoresis alone has insufficient sensitivity for diagnosing AL amyloidosis 1

Monitoring and Follow-up

• Regular assessment of hematologic response is vital to identify non-responders early and shift to rescue treatments 1, 7
• Monitor organ function regularly to assess treatment efficacy and detect complications 1
• Treatment goals include achieving early and profound hematologic response and organ response in the long term 7
• Close collaboration between hematologists, cardiologists, and nephrologists is crucial for effective management 1