Daratumumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | CD38 |
| Legal status | |
| Legal status |
|
| Identifiers | |
| CAS Number |
945721-28-8  |
| ATC code | none |
| ChemSpider | none |
| UNII |
4Z63YK6E0E  |
| Chemical data | |
| Formula | C6466H9996N1724O2010S42 |
| Molar mass | 145,391.67 g·mol−1 |
| (what is this?) (verify) | |
Daratumumab (Darzalex) is an anti-cancer drug. It binds to CD38,[1] which multiple myeloma cells overexpress.[2] Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.[3]
Clinical trials
Encouraging preliminary results were reported in June 2012 from a Phase 1/2 clinical trial in relapsed multiple myeloma patients.[4] Updated trial results presented in December 2012 indicate daratumumab is continuing to show promising single-agent anti-myeloma activity.[5] A 2015 study compared monotherapy 8 and 16mg/kg at monthly to weekly intervals.[2]
In November 2015, the U.S. Food and Drug Administration approved daratumumab for treatment of multiple myeloma.[6][7]
Interference with blood compatibility testing
Daratumumab can also bind to CD38 present on red blood cells and interfere with antibody testing. Patients will show a panreactive antibody panel, including a positive auto-control. Treatment of the antibody panel cells with dithiothreitol (DTT) and repeating testing will effectively negate the binding of daratumumab to CD38 on the RBC surface; however, DTT also inactivates/destroys many antigens on the RBC surface by disrupting disulfide bonds. Fortunately, the only antigen system affected that is associated with common, clinically significant antibodies is Kell, making K-negative RBCs a reasonable alternative when urgent transfusion is indicated.[8]
References
- ↑ World Health Organization (2009). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 101" (PDF). WHO Drug Information 23 (2).
- 1 2 Lokhorst, HM; Plesner, T; Laubach, JP; et al. (2015-09-24). "Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma". The New England Journal of Medicine 373 (13): 1207–1219. doi:10.1056/NEJMoa1506348. ISSN 1533-4406. PMID 26308596.
- ↑ "'Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab'". Janssen Biotech. Retrieved 2013-01-31.
- ↑ "ASCO: Drug Shows Promise in Myeloma". MedPage Today.
- ↑ "'Daratumumab Continues To Show Promise For Relapsed/Refractory Myeloma Patients (ASH 2012)'". The Myeloma Beacon. Retrieved 2013-01-31.
- ↑ http://www.medscape.com/viewarticle/854548?nlid=91686_3663&src=wnl_edit_newsal&uac=78316PX&impID=890536&faf=1
- ↑ http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100115/darzalex-daratumumab
- ↑ Chapuy, CI; Nicholson, RT; Aguad, MD; et al. (June 2015). "Resolving the daratumumab interference with blood compatibility testing.". Transfusion 55 (6 Pt 2): 1545–54. PMID 25764134.