The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China

Abstract

Background: Amyloidosis includes a group of diseases characterized by the extracellular deposition of various fibrillary proteins that can autoaggregate in a highly abnormal fibrillary conformation. The amyloid precursor protein of systemic light-chain (AL) amyloidosis is comprised of monoclonal light chains that are due to plasma cell dyscrasia. The clinical presentation of patients with AL amyloidosis varies from patient to patient. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains. Recent advances in therapy have helped many patients with AL amyloidosis achieve hematologic and organ responses.

Summary: AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The clinical presentation of AL amyloidosis is variable, and the median overall survival was found to be 36.3 months. The disease prognosis and risk stratification are linked to serialized measurement of cardiac biomarkers and free light chains. The treatment of AL amyloidosis is mainly based on chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). The use of novel agents (thalidomide, lenalidomide, and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored.

Key messages: AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The lack of prospective clinical trials using the current therapies is a challenge for evidence-based decision making concerning the treatment of AL amyloidosis.

Facts from east and west: (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by ASCT is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent studies in China and the US indicate that bortezomib induction prior to ASCT increases the response rate. Thalidomide and lenalidomide have shown benefit, but toxicity and lack of clinical evidence exclude these agents from first-line therapy. The green tea extract epigallocatechin-3-gallate is under investigation as an inhibitor of AL amyloid formation and a compound that might dissolve amyloid.

Keywords: Autologous stem cell transplantation; Chemotherapy; China; Clinical presentation; Systemic light-chain amyloidosis.

Figures

Fig. 1

Renal pathologic features for AL amyloidosis. a Periodic acid-Schiff (PAS) stain shows that amyloid appears as amorphous, hyaline, and PAS weakly positive material. b On a trichrome stain, this glomerulus with amyloidosis shows that the amyloid material is pale blue. c Congo red shows accumulation of amyloid in the glomerular mesangium, interstitium, and artery, staining red under light microscopic examination. d Classic apple-green birefringence is elicited on polarized light examination of a Congo red stain. e An electron microscopic (EM) study reveals the typical ultrastructural appearance of amyloid fibrils, characterized by randomly disposed, nonbranching, 8- to 12-nm-diameter fibrils. f, g Extensive accumulation of λ light chains can be clearly identified in the glomerulus and arteriole using immunofluorescence (f ×200; g ×400).

Fig. 2

The incidence of symptoms at presentation between China and Western countries. CHF = Congestive heart failure; OH = orthostatic hypotension.

Fig. 3

Overall survival of all patients and survival of different subgroups according to the clinical characteristics. a Overall survival of all patients. b Survival difference between patients with and without renal insufficiency. c Survival difference between patients with and without heart involvement. d Survival difference between patients with and without liver involvement.