The importance of early diagnosis in amyloidosis


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.


Unmet needs and challenges in AL amyloidosis



While therapeutic options for patients with amyloidosis are increasing and overall survival and outcome are improving, there are still many unmet needs and challenges in this field.3 Clinical trials for amyloidosis have been limited, and many experts agree that awareness and overall education need to be improved. Furthermore, amyloidosis has not seen the same rapid progression in therapeutic modalities that other hematological indications have witnessed.

“I think a greater awareness of the disease is one of the biggest unmet needs. I think that also improving therapies, having more therapies available for patients with AL is going to be very important.”

Novel promising agents and clinical trials in amyloidosis


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.




With the emergence of novel therapeutic agents and an increase in clinical trials, the future treatment landscape of amyloidosis looks promising. Additionally, therapeutic agents used to treat multiple myeloma (MM) are also being translated to the AL landscape, providing patients with this rare disease with more hope in the future.6


  1. Ryšavá R. AL amyloidosis: advances in diagnostics and treatment. Nephrology Dialysis Transplantation. 2019 September; 34, 1460–1466.
  2. Ihne S, Morbach C, Sommer C, et al. Amyloidosis – the Diagnosis and Treatment of an Underdiagnosed Disease. Deutsches Ärzteblatt International. 2020 March 6; 117, 159-166.
  3. The Inaugural Amyloidosis Forum Panelists, Lousada, I. The Amyloidosis Forum: a public private partnership to advance drug development in AL amyloidosis. Orphanet Journal of Rare Diseases. 2020 September 29; 15,
  4. Palladini G, Milani P, Malavasi F, et al. Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis. Cells. 2021 March 4; 10, 545.
  5. Rodriguez M, Lenihan D, Merlini G. Future Developments in Light Chain Amyloidosis Management. The American Journal of Medicine. 2022 April 1; 135, S53-S57.
  6. Lu R, Richards TA. AL Amyloidosis: Unfolding a Complex Disease. Journal of the Advanced Practitioner in Oncology. 2019 November-December; 10, 813-825.
Written by Anya Dragojlovic-Kerkache
Edited by Thomas Southgate

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