Perspectives in treatment of AL amyloidosis

Abstract

Light chain (AL) amyloidosis is the most frequently diagnosed form of systemic amyloid in the western world. The historically poor prognosis of AL amyloidosis appears to be improving with currently reported median survival of c. 40 months compared to 13 months in the early 1990s when low-dose oral melphalan was the mainstay of treatment. Autologous stem cell transplantation (ASCT) achieves the highest rates of complete clonal response but is confounded by substantial treatment-related mortality in AL amyloidosis unless it is restricted to highly selected patients. Newer chemotherapy regimens appear to have a balance of better safety and respectable efficacy with overall outcomes nearly similar to ASCT, but which may be used more widely. There are few data comparing durability, depth of clonal response, rate of organ response and overall survival following ASCT or chemotherapy, but a recent small, randomized trial did not suggest superiority of ASCT to oral melphalan and dexamethasone. There is a compelling need for further and larger randomized trials in this context. At the same time, various new specific anti-amyloid drugs have shown (in early phase studies or animal models) some very promising results. This review attempts to highlight the challenges, controversies and progress in AL amyloidosis.

Diagnosis, Pathogenesis, Treatment, and Prognosis of Hereditary Fibrinogen Aα-Chain Amyloidosis

“…The natural history of the renal decline in AFib was relatively slow compared with that in untreated systemic AL amyloidosis in which median time from diagnosis to ESRD is 7.5 to 14 mo, 23 but was substantially faster than in hereditary apoAI amyloidosis in which it is typically approximately 8 yr. 24 Despite the absence of therapy to diminish production of the amyloidogenic fibrinogen variant in most patients reported here, median patient survival from clinical presentation was more than 15 yr, contrasting markedly that of less than 2 yr and approximately 5 yr among untreated 25 and treated 26,27 patients with systemic AL amyloidosis respectively. Estimated median survival from commencement of dialysis with censoring at transplantation was 9.3 yr, substantially longer than the approximately 5-yr median survival among all nondiabetic U.K. patients aged 55 to 64 yr who commenced dialysis between 1997 and 2001 (Figure 5B).…”

Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis

“…The most frequently affected organs are the kidneys, heart, liver and peripheral nerves. AL amyloidosis is a devastating disease with a median survival of 12-40 months (Kumar et al, 2011;Wechalekar et al, 2008). The incidence of AL is 9 per million per year in the US, comparable to the incidence of Hodgkin's Lymphoma.…”

Corações “Fora do Prazo”: Dois Casos de Amiloidose AL

“…[1][2][3] Continua a ser uma doença de difícil diagnóstico, principalmente nas fases iniciais, e só um elevado índice de suspeição permitirá diagnosticar precocemente estes doentes; facto descrito como determinante no aumento da sobrevida.…”