Systemic light-chain amyloidosis: advances in diagnosis, prognosis, and therapy

Systemic light-chain amyloidosis (AL) is caused by misfolded immunoglobulin light-chain proteins that aggregate and deposit as unique fibrils, ultimately leading to organ failure and death. Recent developments that have significantly aided the management of patients with AL include diagnostic techniques for definitive typing of amyloid deposits by use of laser microdissection with mass spectrometry and customized protein bioinformatics, and validated staging and response-scoring systems that improve clinical trial design. The widespread use of cardiac biomarker staging and serum-free light-chain levels to evaluate response to therapy has also improved care. Standard therapies such as oral melphalan and dexamethasone or autologous stem cell transplant continue to be important options, while thalidomide and its analogs, lenalidomide and pomalidomide, and the proteasome-inhibitor bortezomib have activity in AL and have expanded our armamentarium. Continued improvement in outcomes, however, will require the commitment and cooperation of pharmaceutical companies, regulatory agencies, academic investigators, and cooperative groups/consortia. This effort will involve the conduct of well-designed clinical trials of new agents and combinations within a modern framework that categorizes the study populations of patients with AL, defines the end points appropriate to those populations and to the different phases of clinical trials, employs the newly available staging and response criteria, and standardizes adverse event reporting.