Multiple myeloma is a cancer of the plasma cells of the bone marrow. While advances in therapy have significantly improved patient outcomes over the past decade, relapse is common which emphasises the importance of novel therapies.
Daratumumab is a monoclonal antibody active against the CD38 antigen. CD38 is a glycoprotein that is highly expressed on multiple myeloma cells, yet found at relatively low levels on normal lymphoid and myeloid cells. Binding of daratumumab is thought to result in tumour cell lysis via complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cell-mediated cytotoxicity.
A phase 3 trial evaluated the efficacy of daratumumab in 569 patients with multiple myeloma. The control group received lenalidomide and dexamethasone, while the test group also received daratumumab. The overall response rate was 92.9% in the daratumumab group compared to 76.4% in the control group. The primary endpoint of progression-free survival was also significantly improved at 83.2% compared to 60.1% in the control group at 12-months.
Discontinuation due to adverse effects was slightly lower in the daratumumab group compared to the control group (6.7% vs 7.8%). Fatigue, nausea, neutropenia, thrombocytopenia, and upper respiratory tract infections are frequently reported adverse reactions. Infusion-related reactions are very common, occurring in 46% of initial infusions. However, the incidence of these reactions reduces to just 2-3% for subsequent infusions. Infusion-related reactions can be severe and include bronchospasm, dyspnoea, hypertension, and pulmonary oedema. It is recommended that patients are pre-medicated with a corticosteroid, antipyretic, and antihistamine before each infusion. Corticosteroids are also recommended to be administered after each infusion to prevent delayed reactions. Patients with chronic obstructive pulmonary disease may require additional medications to manage respiratory complications.
- Darzalex (daratumumab) Australian approved product information. Macquarie Park: Janssen-Cilag. Approved July 2017.
- Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016; 375(14): 1319-31.