New data of the ANDROMEDA clinical trial has been presented today in the late breaking session at the 25th European Hematology Association (EHA) Annual Congress which is happening virtual from 11 to 21 June. This study evaluates subcutaneous (SC) daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-CyBorD) compared to CyBorD alone in newly diagnosed patients with AL amyloidosis.
Light chain (AL) amyloidosis is a rare and potentially fatal multi-system disorder that occurs when bone marrow produces abnormal pieces of antibodies called light chains, which clump together to form a substance called amyloid. These clumps of amyloid are deposited in tissues and vital organs and interfere with normal organ function. People who have been diagnosed with this disease are in urgent need of new therapies, as there are currently no approved treatment options.
AL amyloidosis is related to myeloma in two ways. Firstly, it is the abnormal cells in the bone marrow called plasma cells (as in myeloma), which are part of the immune system that makes antibodies to fight infections. The plasma cells make certain type of proteins called immunoglobulins act as antibodies, and they are composed of four protein chains, two lights (called kappa and lambda) and two heavies. In AL amyloidosis patients, plasma cells produce an abnormal immunoglobulin light chain, amyloid, which is deposited in tissues and organs, causing them damage and affecting their functions. Amyloidosis is also related to myeloma in the sense that amyloidosis treatment uses the same procedures and drugs as myeloma treatment.
The ANDROMEDA study
Currently, chemotherapy-based combinations are commonly used in AL amyloidosis, but more effective treatments are needed. Daratumumab is the first and only subcutaneous CD38-directed antibody approved globally to treat myeloma. The Phase 3 ANDROMEDA study evaluated subcutaneous (SC) daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-CyBorD) compared to CyBorD alone in newly diagnosed patients with AL amyloidosis.
Results showed that the primary endpoint, hematologic complete response rate, was 53% for D-CyBorD compared to 18% for CyBorD. The six-month organ response rate was nearly doubled for patients treated with D-CyBorD versus CyBorD, for both cardiac (42% vs. 22%) and renal (54% vs. 27%) responses.
The D-CyBorD combination had an acceptable safety profile consistent with what has been previously observed for daratumumab SC or CyBorD alone. The ANDROMEDA study suggests that daratumumab SC may be a promising treatment for newly diagnosed patients with AL amyloidosis who are in urgent need of new treatment options.