AL amyloidosis
The term amyloidosis is a generic term used to describe a group of rare but serious diseases caused by deposits of abnormal protein, called amyloid, in various tissues and organs of the body. Amyloid is broken down only very slowly and therefore its deposition and subsequent build-up disrupts the function of affected tissues and organs. In AL amyloidosis, the abnormal protein is the light chain that is produced by abnormal plasma cells in the bone marrow (hence the term AL).
AL amyloid can build up in the kidneys, heart, liver, spleen, nerves, or digestive system, and may affect one or more organs at the same time. The pattern of amyloid disposition is unique to each patient but the build-up of amyloid gradually damages the affected organs and tissues, causing symptoms. Usually more than one organ is affected, although AL amyloidosis does not normally affect the brain. This means a number of different physicians and teams may be involved in the initial diagnosis, such as nephrology, cardiology and gastroenterology.
AL amyloidosis is a relatively rare disease: approximately 500 patients are diagnosed in the UK each year. Between 10 – 20% of myeloma patients develop AL amyloidosis at some stage during the course of their myeloma, which often goes unrecognised but leads to a poorer prognosis, greater morbidity and decreased survival compared to those without AL amyloidosis. Only a very small percentage of myeloma patients at diagnosis also have concurrent symptomatic AL amyloidosis.
In order to diagnose and monitor AL amyloidosis, it is necessary to carry out a number of tests and investigations including the Serum Free Light Chain Assay, tissue biopsies, bone marrow biopsies, full blood count, kidney function tests and if confirmed, a Serum Amyloid Protein (SAP) scan.
First-line treatment for AL amyloidosis is now DaraCyBordD (a treatment combination of daratumumab, cyclophosphamide, bortezomib and dexamethasone). It can be very effective at halting its progress; however, there is, as yet, no cure and patients eventually relapse, with treatment following that of myeloma. Newer treatments targeting the breakdown of the amyloid deposits are also being tested.
Further reading
Palladini G et al. (2020) Management of AL amyloidosis in 2020. Blood. 136:2620-27