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KEY CONCEPTS
Systemic light chain (AL) amyloidosis is a rare protein deposition disease typically found accompanied by an indolent plasma cell dyscrasia, although it can also be found concomitantly with multiple myeloma.
In the systemic presentation (some cases are localized), commonly affected organs may include the heart, kidneys, liver, gastrointestinal tract, and peripheral nervous system.
Diagnosis requires histologic evidence of amyloid deposition in tissues either by aspiration of abdominal subcutaneous fat or biopsy of the organs involved, with the demonstration of clonal plasma cell disorder and abnormal free light chain in serum or urine.
Historical cohorts of patients with severe cardiac involvement have a poor prognosis of 4 to 6 months, though recent studies show this can be greatly improved with successful treatment.
Plasma cell–directed therapy with or without high-dose melphalan and autologous stem cell rescue is the treatment of choice for patients with confirmed systemic AL.
Multidisciplinary care is beneficial because these patients have distinct clinical presentations, symptoms, and risks compared with patients with other plasma cell dyscrasias.
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Systemic light chain (AL) amyloidosis is a rare plasma cell proliferative disorder. It results from organ deposition of amyloid fibrils that consist of the NH2-terminal amino acid residues of the variable portion of the light chain immunoglobulin molecule. The estimated age-adjusted incidence is nine to 14 cases per million person-years, and around 4000 new cases are estimated annually in the United States. About 75% of cases are derived from lambda light chain. AL amyloidosis typically results primarily from a small plasma cell clone in the bone marrow or may rarely be associated with another B-cell malignancy. Coexisting AL amyloid deposits are identified in 10% to 15% of patients with multiple myeloma (MM).
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The commonly affected organs include the heart, kidneys, liver, gastrointestinal tract, and peripheral nervous system. This leads to clinical symptomatology of nephrotic syndrome, cardiomyopathy, hepatomegaly, neuropathy, macroglossia, anemia, carpal tunnel syndrome, and periorbital purpura. Prognosis is driven primarily by the extent and severity of cardiac involvement with patients having severe cardiac involvement being at high risk for early death, although this risk is somewhat abrogated with successful plasma cell–directed treatment. However, beyond overall survival (OS), patients with AL often have chronic symptoms relating to the morbidity of amyloid organ involvement and decreased quality of life. The exact pathophysiology of organ or tissue damage in AL amyloidosis is not completely understood, but the reduction of serum free light chain concentration after chemotherapy treatment results in improved cardiac function and suggests that both circulating amyloidogenic free light chains in addition to those deposited play an important role in organ dysfunction. New therapies targeting the underlying plasma cell clone are improving hematologic response rates and potentially patient survival with the disease, and therapies that directly target the already deposited light chain amyloid continue in development at this time.
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EPIDEMIOLOGY AND RISK FACTORS
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Light chain amyloidosis is typically ...