Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis

Abstract

Subcutaneous daratumumab (DARZALEX^®) co-formulated with recombinant human hyaluronidase (DARZALEX FASPRO^®) is approved in several countries, including the USA and those of the EU, for use in combination with bortezomib, cyclophosphamide and dexamethasone for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis. Daratumumab is a CD38-targeting, human IgG1κ monoclonal antibody. In the pivotal phase III ANDROMEDA trial in adults with newly diagnosed systemic AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide and dexamethasone significantly increased the proportion of patients achieving a haematological complete response relative to bortezomib, cyclophosphamide and dexamethasone alone (primary endpoint). Daratumumab combination therapy produced rapid and deep haematological responses which were associated with improved major organ deterioration progression-free survival (PFS). The addition of daratumumab also led to higher cardiac and renal response rates at 6 and 12 months. Daratumumab had an acceptable tolerability profile when used as combination therapy. Therefore, daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone represents an important emerging first-line treatment option for patients with systemic AL amyloidosis.

Plain Language Summary

Systemic AL amyloidosis is a rare protein misfolding disease that causes serious damage to different organs, especially the heart and kidneys. Daratumumab (DARZALEX^®) is a human monoclonal antibody that targets CD38, a protein expressed on clonal plasma cells. A subcutaneous formulation of daratumumab, co-formulated with recombinant human hyaluronidase (DARZALEX FASPRO^®), is approved for use in adult patients with newly diagnosed AL amyloidosis. When used in combination with bortezomib, cyclophosphamide and dexamethasone, daratumumab was associated with higher rates of haematological complete response and prolongation of major organ deterioration PFS compared with bortezomib, cyclophosphamide and dexamethasone alone. The addition of daratumumab was also associated with near doubling of cardiac and renal response rates at 6 and 12 months. Subcutaneous daratumumab had an acceptable tolerability profile when used as combination therapy, with no new safety concerns. The combination of daratumumab with bortezomib, cyclophosphamide and dexamethasone is an important emerging treatment option for patients with newly diagnosed systemic AL amyloidosis.