From the Guidelines
Amyloidosis is a group of diseases caused by the accumulation of abnormal proteins in tissues and organs, and early diagnosis and treatment are crucial to prevent progressive organ damage, with the most recent and highest quality study recommending a comprehensive approach to diagnosis and management 1.
Types of Amyloidosis
- AL (light chain) amyloidosis, associated with bone marrow disorders
- AA amyloidosis, occurring with chronic inflammatory conditions
- ATTR amyloidosis, which can be hereditary or age-related ### Diagnosis and Treatment
- Diagnosis typically involves tissue biopsy to confirm the presence of amyloid proteins
- Treatment depends on the type of amyloidosis and may include chemotherapy for AL amyloidosis, anti-inflammatory medications for AA amyloidosis, or specific medications like tafamidis for ATTR amyloidosis
- The absence of cardiac symptoms, such as chest pain, fatigue, and shortness of breath, is crucial in the diagnosis of cardiac amyloidosis, and recurrent testing may be necessary to identify cardiac involvement 1 ### Organ Involvement
- Amyloid deposits can affect various organs, including the heart, kidneys, liver, nervous system, and gastrointestinal tract
- Cardiac biomarkers, such as NT-proBNP and Troponin T, are used for staging and have high diagnostic sensitivity, with all patients with heart involvement having an elevated NT-proBNP 1 ### Management and Prognosis
- Early recognition and initiation of treatment are vital to prevent irreversible organ damage
- Autologous stem cell transplantation (ASCT) remains the standard of care and first-line treatment in a small proportion of patients, while new first-line agents, such as bortezomib, have improved outcomes in ASCT-ineligible patients 2
From the Research
Amyloidosis Overview
- Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues 3
- The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis 3
Treatment of AL Amyloidosis
- Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement, or at least stabilization of organ function in most responding patients 4
- The combination of oral melphalan and dexamethasone is considered standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation 5
- The addition of bortezomib to melphalan and dexamethasone (BMDex) has been shown to improve response rates, but not necessarily overall survival, in some patient populations 6
Treatment Outcomes
- A phase II trial of melphalan, lenalidomide, and dexamethasone for the treatment of immunoglobulin light chain amyloidosis reported a complete remission rate of 18% and an overall organ response rate of 48% 4
- A matched case-control study of 174 patients with newly diagnosed AL amyloidosis found that BMDex resulted in a higher rate of complete responses (42% vs 19%) compared to melphalan and dexamethasone alone, but did not improve overall survival in the entire population 6
- A long-term study of oral melphalan and dexamethasone in 259 patients with AL amyloidosis reported a median survival of 7.4 years in the full-dose group and 20 months in the attenuated-dose group 5
Prognostic Factors
- Independent prognostic determinants for survival in AL amyloidosis include the use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy 5