Amyloidosis is a collection of diseases characterized by the deposition of insoluble amyloid fibrils in various organs, resulting in multi-organ damage.¹ Light chain (AL) amyloidosis is one of the most common forms of the disease, with diagnosis and treatment remaining a challenge due to the vague and nonspecific clinical manifestations of the illness.² Early diagnosis and increased awareness of amyloidosis are crucial to improving patient survival and outcomes.

In this video, Angela Dispenzieri, MD, Mayo Clinic, Rochester, MN, highlights the importance of early diagnosis and detection in AL amyloidosis and the need to consider patients who present with monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma as possible AL patients.

The Phase III ANDROMEDA trial (NCT03201965) transformed the amyloidosis treatment landscape. This trial investigated subcutaneous daratumumab plus bortezomib, cyclophosphamide and dexamethasone (Dara-VCd) versus VCd alone. Results from this trial indicated that dara-VCd was well tolerated, and patients demonstrated a high organ response rate as well as improved cardiac and renal function.⁴ These findings ultimately led to the FDA approval of daratumumab for AL amyloidosis.

The promise of monoclonal antibodies (mAbs) for the treatment of amyloidosis as observed in the ANDROMEDA trial has led to a variety of other mAbs being considered and further investigated, including isatuximab, belantamab mafodotin, and elotuzumab.⁵ More recently, novel agents including CAEL-101 and NEOD001, which directly target the misfolded amyloid deposits, are also being investigated.

Several other clinical trials are currently ongoing in the field of amyloidosis, including the AFFIRM-AL trial (NCT04973137) investigating the safety and efficacy of birtamimab, the EMN27 trial (NCT04617925) investigating the use of belantamab mafodotin, and the TOURMALINE-AL1 trial (NCT01659658) investigating the use of ixazomib.