Treatment of immunoglobulin light chain amyloidosis

Abstract

No therapy is uniformly effective in the management of immunoglobulin light chain amyloidosis (AL amyloidosis). Despite the common generalization, therapy is highly effective. Options available to patients with AL amyloidosis include high-dose therapy, but this is applicable to only about one fourth of patients. Therapies shown to be effective are based on alkylators, dexamethasone, or combinations of an alkylator and steroids. In the past 5 years, novel agents previously shown to be effective in multiple myeloma (eg, thalidomide, lenalidomide, and bortezomib) have been shown to have efficacy in the management of AL amyloidosis. Predictors of outcome include the serum brain natriuretic peptide, the number of organs involved, and the severity of cardiac involvement detected by echocardiography. Virtually all patients are candidates for a trial of therapy, and it is possible to find a nontoxic regimen that can be administered to virtually any patient.

Recent Improvements in Survival in Primary Systemic Amyloidosis and the Importance of an Early Mortality Risk Score

“…3,27 The combination of melphalan and prednisone had been the mainstay of therapy until a decade or 2 ago, but several therapeutic options have become available in the past 10 to 15 years. 28,29 These include high-dose therapy and SCT, the combination of melphalan and dexamethasone, and more recently the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide used alone or in combination.…”

Light chain (AL) amyloidosis: update on diagnosis and management

“…The average treatment related mortality (TRM) in four single center studies is 21% but has been reported as high as 39%[26]. Patients with cardiac involvement and autonomic dysfunction are particularly susceptible to fluid shifts and hypotension as the result of high-dose G-CSF and must be monitored during all phases of treatment including mobilization/collection.…”

The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44

“…7,8 Therapy is primarily directed to eradicating the plasma cell clone. [9][10][11][12] Free LC production is frequently observed in plasma cell disorders, including monoclonal gammopathy of undetermined significance, multiple myeloma, and Waldenström macroglobulinemia, but only a fraction of free LC can lose solubility and organize into amyloid deposits. 13 Research has focused on the properties of amyloid-forming LC, and specifically on the variable (V) region, and this for the following reasons: (1) the V region is the amino terminal portion of the Ig LC deputed to antigen binding and responsible for its sequence variation because it is formed via a somatic rearrangement of one of a multitude of germline gene VL segments to one of few joint (J) segments; (2) amyloid deposits are constituted of fragments of LC, comprising the V region and parts of the constant region; and (3) characteristic of AL amyloidosis is the predominance of the isotype over (3:1 ratio), suggesting a genetic propensity in V segments.…”