What is the treatment approach for amyloidosis?

Treatment Approach for Amyloidosis

The treatment of amyloidosis requires a type-specific approach, with AL amyloidosis primarily treated with plasma cell-directed therapies like daratumumab-CyBorD, while ATTR amyloidosis is treated with TTR stabilizers such as tafamidis. 1, 2

Classification and Diagnosis

• Accurate typing of amyloid is essential as treatment differs significantly between types 1
• AL amyloidosis requires serum free light chain assay, serum immunofixation electrophoresis, and urine immunofixation electrophoresis for diagnosis 1
• ATTR amyloidosis can be diagnosed non-invasively using technetium scintigraphy 3

Treatment of AL Amyloidosis

First-line options:

• For transplant-eligible patients:

  • High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 4, 1
  • Daratumumab-CyBorD (cyclophosphamide, bortezomib, dexamethasone) may supplant HDM/SCT as first-line therapy 4, 1

• For transplant-ineligible patients:

  • Daratumumab-CyBorD is the preferred first-line regimen 4, 1
  • Alternative: CyBorD alone 4

Medication considerations:

• Daratumumab: Monitor for cardiac failure (12%), arrhythmias (8%), and atrial fibrillation (6%) 4, 1
• Proteasome inhibitors (bortezomib): Risk of Grade 3 heart failure and decreased LVEF 4, 1
• Corticosteroids: Monitor for fluid overload and pulmonary edema 4, 1

Treatment of ATTR Amyloidosis

• Tafamidis (VYNDAQEL/VYNDAMAX) is FDA-approved for both wild-type and hereditary ATTR cardiomyopathy 2
  • Dosage: VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily 2
  • Reduces cardiovascular mortality and cardiovascular-related hospitalization 2
• Historical options included liver transplantation for hereditary ATTR 4, 5
• Emerging therapies include TTR silencers and TTR fibril disruptors 6

Management of Organ-Specific Complications

Cardiac Involvement

• Cardiac involvement is the main driver of disease prognosis and mortality 1
• Heart transplantation may be considered in select patients without significant extracardiac involvement 4
• Temporary mechanical circulatory support may be used as bridge to transplantation 4

Gastrointestinal Involvement

• Dietary modifications: small evening meals, longer intervals between evening meal and lying down 4
• Medications for symptom management:
  • Nausea/early satiety: ondansetron (4-8 mg every 4-8h), metoclopramide (10-20 mg every 6-8h) 4
  • Diarrhea: loperamide (2-4 mg 4 times daily), diphenoxylate/atropine (2.5-5 mg 4 times daily) 4
  • Small intestinal bacterial overgrowth: rifaximin, metronidazole 4

Palliative Care

• Palliative care should be integrated early in the disease course 4
• Referral to palliative care is recommended when physical symptoms (intractable heart failure, neuropathy, orthostasis, GI distress) or emotional/spiritual distress interfere with quality of life 4
• Key interventions include:
  • Assessment of goals, values, and preferences 4
  • Early symptom management 4
  • Psychological support 4
  • Support system for family to cope with bereavement 4

Monitoring and Follow-up

• Regular assessment of hematologic response in AL amyloidosis 1
• Monitoring for cardiac decompensation during therapy 1
• Evaluation of organ function improvement 1

Common Pitfalls and Caveats

• No absolute contraindications to plasma cell-directed therapies based on ejection fraction or cardiac status in AL cardiac amyloidosis 1
• Patients with AL amyloidosis are at higher risk for treatment-related toxicity than those with multiple myeloma 1
• VYNDAMAX and VYNDAQEL are not substitutable on a per mg basis 2
• Tafamidis may cause fetal harm based on animal studies; advise against breastfeeding 2