A Look at the Current State of Drug Treatments for Amyloidosis
Amyloids are formed from handful of types of misfolded proteins that interact to form insoluble deposits in tissues. The presence of amyloid grows with aging, and eventually causes the serious, fatal disruption of tissue function found in the family of amyloidosis conditions. The best approach to dealing with amyloid is to simply remove it, such as by using immune therapies of the sort currently in early stage trials for Alzheimer's disease. These are treatments that aim to use the immune system to break down harmful amyloid aggregates, and success should lead to a general technology platform that can be turned against any form of amyloid.
There is a way to go towards this goal, however, and in the meanwhile the present state of drug-based therapies for various forms of fatal amyloidosis is better than nothing but leaves a lot to be desired. As is still the case for many forms of cancer, the mainstream focus is on improving survival on a scale of adding additional months or a few years to remaining life, and reuse of existing drugs is always the first thing to be tried rather than the development of entirely new technologies:
The outcomes and responses to treatment remain poorly studied among patients with systemic AL amyloidosis who require further treatment following prior novel agent-based therapy. We report here treatment with lenalidomide-dexamethasone in 84 AL amyloidosis patients with relapsed/refractory clonal disease following prior treatment with thalidomide (76%) and/or bortezomib (68%).On an intention-to-treat (ITT) basis, the overall haematological response rate was 61%, including 20% complete responses. The median overall survival (OS) has not been reached; 2-year OS and progression-free survival (PFS) was 84% and 73%, respectively. Achieving a free light chain (FLC) response was an independent good prognostic factor for OS in multivariate analysis. There was no impact of prior thalidomide or bortezomib therapy on response rate, OS or PFS. 16% achieved an organ response at 6 months, with a marked improvement in organ responses in patients on long term therapy (median duration 11 months) and 55% achieving renal responses by 18 months.
Lenalidomide/dexamethasone therapy achieves good haematological responses in patients with AL amyloidosis with relapsed/refractory clonal disease. The rate of renal responses among patients who received prolonged treatment was unexpectedly high, raising the possibility that immunomodulatory effects of lenalidomide therapy might enhance the otherwise slow natural regression of amyloid deposits.