Daratumumab Regimen May Be the More Active Therapy Needed for Amyloidosis

Efstathios Kastritis, MD, a professor of medical oncology at the National and Kapodistrian University of Athens, in Athens, Greece, discusses the amyloidosis setting, current standards of care, and the phase 3 ANDROMEDA trial (NCT03201965).

Amyloid light-chain (AL) amyloidosis is a rare disease caused by clonal plasma cells that produce light chains that form amyloid fibers, which attach to parts of the body like the heart and kidneys. To treat patients with this disease, these cytotoxic immunoglobulin light chains need to be eliminated. The treatments use for amyloidosis are based on those used in patients with multiple myeloma, but with some adjustments and modifications for toxicity issues, according to Kastritis.

The standard in this setting is combination regimens using bortezomib (Velcade). However, Kastritis believes more active therapies are needed since not all patients can achieve rapid hematologic responses and rapid reduction of free light chains in this setting. Daratumumab (Darzalex) is a monoclonal antibody which targets CD38 and is active in patients with multiple myeloma. It has also shown activity in patients with AL amyloidosis. Daratumumab also has low toxicity.

By combining daratumumab with bortezomib, cyclophosphamide, and dexamethasone, Kastritis and his fellow investigators believed it could further improve the outcomes for this patient population. The ANDROMEDA study is investigating this combination to see if it will improve the complete hematologic response rates and overall responses of patients with AL amyloidosis.