Clinical trials evaluating potential therapies for light chain (AL) amyloidosis

ABSTRACT

Introduction: The field of systemic amyloidosis is experiencing major advances in diagnostic and prognostic methods coupled with a growing availability in treatment options.

Areas covered: Treatment of AL amyloidosis traditionally targeted the clonal plasma cells, in order to block further production of amyloidogenic light chains. Currently, a research focus is placed on targeting the already formed amyloid deposits using monoclonal antibodies against epitopes on such deposits. Encouraging results were obtained from the three investigated antibodies: NEOD001, 11-1F4 and anti-SAP, but further validation is required before these antibodies can be commercialized. In this paper, we review the current active clinical research in AL amyloidosis, which includes the monoclonal antibodies targeting amyloid deposits, daratumumab, Venetoclax, doxycycline, green tea, pomalidomide, carfilzomib and ixazomib.

Expert opinion: Monoclonal antibodies, targeting either the amyloid deposits or the plasma cell compartment will likely be integrated into routine treatment practice given their encouraging results and minimal toxicity in the fragile population of AL amyloidosis. Other therapeutic options hold promise to the field as well, but toxicity will likely challenge their routine use. Early recognition remains the best option for outcome enhancement.

KEYWORDS:

• Monoclonal antibody
• research
• clinical-trials
• amyloid

Article highlights

• AL amyloidosis has seen improvement in patient outcomes following the recent introduction of novel therapies

• New therapies targeting the amyloidogenic plasma cells further expand the armamentarium and should provide further improvement in patient outcome

• Monoclonal antibodies targeting the amyloid deposits represent a novel approach for AL amyloidosis management. These antibodies demonstrated encouraging results in early phase clinical trials, and may be incorporated into routine practice in the future, pending the results of phase 2/3 trials.

• With the emergence of effective therapies, the importance of early diagnosis cannot be overemphasized

This box summarizes key points contained in the article.

Declaration of interest

M Gertz has received honoraria not related to publication of this manuscript from Celgene, Prothena, and Amgen. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded