A very important and yet unmet therapeutic goal in AL amyloidosis treatment is the removal of amyloid deposits that are already present in organs at the time of diagnosis, as it could lead to the restoration of organ function. The most common approach under investigation is the use of immunotherapeutic drugs called monoclonal antibodies. These antibodies enable the immune system to recognise the deposits, which enables the body to remove them. For example, two ongoing clinical studies are investigating the efficacy of CAEL-101 in combination with chemotherapy, a monoclonal antibody that binds to AL amyloid deposits; hence it may trigger the immune system-mediated removal of these deposits. Another similar monoclonal antibody, NEOD001 functions in the same way in aiding the body to remove amyloid deposits. However, the phase III clinical trial investigating its efficacy was terminated in 2019 due to no significant therapeutic improvement compared to the control group. That said, a subgroup analysis allowed to identify a possible effect in the advanced stage of the disease. So, a clinical trial using birtamimab (formerly known as NEOD001) is underway.

Since myeloma and AL amyloidosis have a shared pathophysiology, myeloma treatments may benefit AL amyloidosis patients as well. For example, carfilzomib, the second-generation proteasome inhibitor is being investigated as an alternative treatment option for AL amyloidosis. However, due to possible cardiac toxicity it should be considered only in selected cases of patients with non-severe cardiac damage or isolated peripheral neuropathic involvement. Another agent from the same class, ixazomib is also being tested, as this medication is known to have a safer side effect profile with regards to cardiac toxicity (see factsheet on ixazomib). A phase III trial of ixazomib-dexamethasone versus standard of care (TOURMALINE-AL1) was concluded. A chemotherapeutic agent called bendamustine, which is commonly used in non-Hodgkin lymphoma and in myeloma, has also shown efficacy in AL amyloidosis patients. Other options under investigation are: belantamab mafodotin, venetoclax and the applicability of CAR-T cell approach to selected patients with AL amyloidosis.

MPE publishes a conference report after major scientific summits like the American Society of Clinical Oncology (ASCO), the European Hematology Association (EHA) or the American Society of Hematology (ASH); these reports summarise the novel therapeutic options in the field of myeloma and AL amyloidosis. If you are interested in reading about further novel therapeutics under investigation for AL amyloidosis, please visit the “Conference reports” section of our website.