Treatment of Immunoglobulin Light Chain (Primary or AL) Amyloidosis

Not all forms of amyloidosis are systemic. Some patients may present with a localized form and should not be treated with chemotherapy. Some patients with systemic amyloidosis may have secondary, familial, or dialysis-related types. These types are not responsive to chemotherapy. Immunoglobulin light chain (primary or AL) amyloidosis is a plasma cell dyscrasia. Suppression of light chain production translates to organ response, improved organ function, and improved quality of life. This review of the various available options for the treatment of systemic amyloidosis is designed to help the clinician determine which patients are candidates for stem cell transplantation and which should be treated with conventional chemotherapy. The role of the recently introduced novel agents in management of amyloidosis is also reviewed.

Amyloidosis results from the misfolding of a protein from the native alpha helical state into a beta-pleated sheet. This equilibrium between a soluble precursor and an insoluble end product (the fibril) can be impacted by destabilizing the amyloid fibril protein, and research is under way to cause fibril dissolution, by interfering with binding of the amyloid P component or via antibodies against the fibril itself,[1] that leads to shrinkage of amyloid tumors.[2] These strategies are in early investigative stages, and the only available therapies in the clinic result in reduction of the precursor light chain protein supply, which leads to synthesis of the amyloid fibril. In virtually every instance, the available effective therapy is cytotoxic chemotherapy directed against the plasma cell, the source of amyloid light chain production.

FIGURE 1

Algorithm for diagnosis of suspected amyloidosis

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