From the Guidelines
Amyloidosis is a plasma cell dyscrasia in the case of AL amyloidosis, which is caused by abnormal plasma cells producing misfolded immunoglobulin light chains. The management of AL amyloidosis depends on the presence and severity of heart dysfunction, and initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens 1.
Key Considerations
- AL amyloidosis is closely related to multiple myeloma and other monoclonal gammopathies, and its treatment is derived from anti–plasma-cell multiple myeloma therapies 1.
- The goal of treatment of AL amyloidosis is to eradicate the pathological plasma cells and remove the affected light chain from the circulation 1.
- Other types of amyloidosis, such as AA amyloidosis, ATTR amyloidosis, and familial forms of amyloidosis, are not plasma cell dyscrasias and involve different proteins and pathophysiological mechanisms.
Treatment Approaches
- Plasma cell-directed therapies like bortezomib, lenalidomide, or autologous stem cell transplantation may be appropriate for AL amyloidosis but not for other types 1.
- The treatment of AL amyloidosis should be individualized based on the patient's specific condition and the presence of heart dysfunction or other organ involvement 1.
From the Research
Definition and Classification
- Amyloidosis is characterized as a plasma cell dyscrasia in multiple studies 2, 3, 4, 5.
- This classification is based on the production of abnormal immunoglobulin light chains that accumulate in tissues and cause organ dysfunction 4.
Pathophysiology
- The disease is caused by the misfolding of proteins that deposit in organs, leading to progressive organ damage and impairment of quality of life 5.
- Amyloid aggregates or preceding intermediaries cause direct cell damage through their proteotoxicity, and amyloid deposits distort tissue architecture, eventually leading to organ impairment 6.
Diagnosis and Management
- The diagnosis of amyloidosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease 3.
- Management should be multidisciplinary, with supportive management tailored to management of organ dysfunction being paramount to survival and minimization of treatment-associated toxicity 6.
- Treatment is tailored to the initial risk assessment of the patients, with regimens adapted from the expanding options available for multiple myeloma patients 6.