From the Guidelines
The treatment approach for pulmonary amyloidosis should prioritize chemotherapy regimens targeting the underlying plasma cell dyscrasia, such as combinations of bortezomib, cyclophosphamide, and dexamethasone, or melphalan with dexamethasone, as these have shown to improve survival and quality of life in patients with AL amyloidosis 1.
Treatment Overview
The treatment of pulmonary amyloidosis depends on the specific type and clinical presentation of the disease. For localized tracheobronchial amyloidosis, bronchoscopic interventions like laser ablation, mechanical debulking, or stent placement may be used to relieve airway obstruction.
- Systemic therapies are required for diffuse parenchymal disease, particularly when associated with systemic amyloidosis.
- For AL amyloidosis, chemotherapy regimens are used, including combinations of bortezomib, cyclophosphamide, and dexamethasone, or melphalan with dexamethasone.
- Autologous stem cell transplantation may be considered in eligible patients, with a treatment-related mortality of approximately 3% in experienced centers and a median survival of over 15 years in patients achieving a complete response 1.
Specific Treatment Options
- For ATTR amyloidosis, tafamidis (20 mg daily) or patisiran may be used to stabilize transthyretin proteins.
- Supportive care is essential and includes oxygen therapy for hypoxemia, diuretics for heart failure symptoms, and pulmonary rehabilitation.
- Treatment response should be monitored through pulmonary function tests, imaging, and serum free light chain levels in AL amyloidosis.
Recent Guidelines and Recommendations
- The 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis recommends considering high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) for highly selected patients, with a median survival of over 15 years in those patients achieving a complete response 1.
- The European Myeloma Network recommends ASCT as an important treatment option in the treatment of AL amyloidosis, with hematologic response rates exceeding 70% and a median survival of 7.6 years 1.
From the Research
Treatment Approach for Pulmonary Amyloidosis
The treatment approach for pulmonary amyloidosis, specifically for AL amyloidosis, involves several options, including:
- High-dose melphalan with autologous stem cell transplantation (HDM/SCT) 2, 3
- Oral melphalan and prednisone 2
- Oral melphalan, dexamethasone, and thalidomide (MTD) for patients with advanced cardiac AL amyloidosis 4
- Novel agents, including proteasome inhibitors, immunomodulators, and monoclonal antibodies, for both frontline and relapsed settings 5
- Orthotopic heart transplantation (OHT) followed by ASCT for selected patients 5
Patient Selection and Risk-Adapted Approach
Patient selection is crucial for the treatment of AL amyloidosis, and a risk-adapted approach to melphalan dosing can be used to minimize toxicity and improve outcomes 3. Factors such as patient age, extent of organ involvement, and cardiac function should be considered when selecting patients for treatment.
Emerging Therapies
Newer therapies, including pharmacologic agents such as diflunisal, tafamidis, and doxycycline, are being investigated for the treatment of cardiac amyloidosis, and may also be applicable to pulmonary amyloidosis 5, 6. Additionally, monoclonal antibodies targeting misfolded proteins and CRISPR-Cas9-based drugs are being developed and may offer new treatment options for patients with pulmonary amyloidosis 6.
Management of Symptoms
Best supportive care and management of symptoms, such as heart failure symptoms with diuretics, are also important aspects of treatment for pulmonary amyloidosis 5.