Results from the ANDROMEDA trial showed that Darzalex Faspro (daratumumab and hyaluronidase human-fihj) was an effective treatment for patients with light-chain (AL) amyloidosis.

DocWire News spoke with study co-author Raymond Comenzo, MD, Director of Transfusion Medicine and Professor at the Tufts University School of Medicine about these findings, which were featured at the American Society of Hematology (ASH) 2020 virtual annual conference (abstract #552).

DocWire News: Today, we’re talking about data that will be presented at the upcoming ASH 2020 annual conference regarding the phase III ANDROMEDA study, illustrating the promise of Darzalex Faspro as a potential treatment for patients with light-chain amyloidosis. Dr. Comenzo, can you just walk us through some of the highlights of this study?

Raymond Comenzo, MD: I think it’s very important to start with the fact that there are no approved drugs to treat patients with light-chain amyloidosis. This is a disease in which plasma cells in the bone marrow that are clonal, make a protein that deposits in the body’s organs, notably in the heart and kidneys, and without elimination of these plasma cells in the bone marrow, patients to die in a matter of months to a few years.

The use of immunotherapy in the form of anti-CD38 monoclonal antibody therapy, which that tumor map provides, is an extremely important advance in the treatment of these patients. In the clinical trial ANDROMEDA, a standard approach with chemotherapy using bortezomib, cyclophosphamide, and dexamethazone was compared with that standard approach, plus daratumumab. A critical aspect of daratumumab in this trial was that it was a 15 milliliter infusion under the skin, lasting maybe four or five minutes for the infusion itself, but it did not require intravenous fluids. Patients with light-chain amyloid and heart involvement, they get into trouble if too much intravenous fluid is administered to them.

The trial is completed. The results will be presented at ASH following up on the initial presentations at the European Hematology Association meeting in June, and the results showed that the combination of daratumumab with chemotherapy was far better than chemotherapy alone in achieving very prompt elimination of the plasma cells in the bone marrow in over 50% of patients, allowing their organs to improve, and hopefully allowing them to live longer.

DocWire News: What are some hopeful clinical implications of these results?

Dr. Comenzo: We’re at a time in amyloid therapies when the existence of effective treatments will accelerate the diagnosis of the disease itself. It provides an incentive for physicians to make the diagnosis because they can then offer therapy. This applies to all the different types of amyloid that can cause heart involvement. There are three major types, two of them related to a molecule called transthyretin, and one related to light chains, the AL type which we’re speaking about today. This will change the timing of the diagnosis and the timing of the beginning of therapy with an extremely effective combination. Should it be approved by the FDA, which we all anticipate, this will enable patients to get better faster, and will enable more patients to survive with AL amyloidosis.

DocWire News: What’s next for you and your research team on this project or going forward?

Dr. Comenzo: Well, there are potential combinations of monoclonal antibodies, as well as monoclonal antibodies that are linked to both other monoclonals that will bring immune cells closer to the culprit plasma cells, and also linked to drugs. So I anticipate that there will be many significant phase II studies using combinations of monoclonal antibodies, and also that some of the newer medicines that have been developed for multiple myeloma may indeed be relevant to patients with light chain amyloid. So having an effective initial therapy means that patients will survive longer, and if and when they relapse, hopefully we’ll have more effective therapies available to them at that time.