Primary systemic
immunoglobulin light chain (
AL) amyloidosis is caused by a plasma cell clone of, usually low, malignant potential that expresses CD38 molecules on their surface. Treatment of
AL amyloidosis is based on the elimination of the plasma cell clone. The combination of
cyclophosphamide-
bortezomib-
dexamethasone (CyBorD) is the most widely used and is considered a standard of care; however, complete hematologic response rates and organ response rates remain unsatisfactory.
Daratumumab, an anti-CD38
monoclonal antibody, has demonstrated encouraging results, with rapid and deep responses, in patients with relapsed or refractory
AL amyloidosis as monotherapy with a favorable toxicity profile. The large phase-III, randomized, ANDROMEDA study evaluated the addition of
daratumumab to CyBorD in previously untreated patients with
AL amyloidosis and demonstrated that addition of
daratumumab can substantially improve hematologic complete response rates, survival free from major organ deterioration or hematologic progression, and organ responses. In this review, we discuss the role of
daratumumab in the treatment of
AL amyloidosis, its mechanism of action, and the results of ANDROMEDA study that led to the first approved
therapy for
AL amyloidosis.