The hallmark of amyloidosis is the deposition in body tissues of protein fibrils associated with organ dysfunction. The most frequent type of systemic amyloidosis is amyloid light-chain (AL) amyloidosis, a rare disease caused by a small, dangerous B cell clone that produces misfolded light chains which form amyloid deposits, thus causing rapid deterioration of organ function. In this lecture, Dr. Giampaolo Merlini will discuss the advances in understanding the multifaceted molecular mechanisms of amyloid disease and the complexity of its management. The distinct biology of the amyloidogenic clone and its vulnerability to specific drugs will be presented together with genetic changes that modulate treatment response. Dr. Merlini will outline the vital importance of early diagnosis, when target organ damage is still recoverable, following intervention. Furthermore, he will describe the central role of cardiac biomarkers in the management of AL amyloidosis – from diagnosis to risk stratification and assessment of response to therapy. The complexity and pitfalls of the diagnostic procedure will be illustrated. Patients are fragile and highly sensitive to treatment toxicity, requiring a risk-adapted approach which will be discussed in the context of several effective anti-clone drugs and regimens now available. Early cardiac death still occurs in nearly one-third of very high-risk patients and is a major, unresolved clinical problem. Novel drugs are enriching the therapeutic landscape, and immunotherapies aimed at accelerating the reabsorption of amyloid deposits are under evaluation in several clinical trials. The future lies in combination therapy, with anti-clone therapy combined with newer treatments holding promise of further improving survival in this very treatable disease.
Kenneth C. Anderson
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