Daratumumab

Daratumumab
Monoclonal antibody
Type Whole antibody
Source Human
Target CD38
Clinical data
ATC code none
Legal status
Legal status
Identifiers
CAS Number 945721-28-8 N
ChemSpider none
UNII 4Z63YK6E0E YesY
Chemical and physical data
Formula C6466H9996N1724O2010S42
Molar mass 145,391.67 g·mol−1
 NYesY (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 16 mg/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] In May 2016 daratumumab was also conditionally approved by the European Medicines Agency for treatment of multiple myeloma.[8]

Interference with blood compatibility testing

Daratumumab can also bind to CD38 present on red blood cells and interfere with routine testing for clinically significant antibodies. Patients will show a panreactive antibody panel, including a positive auto-control, which tends to mask the presence of any clinically significant antibodies. 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 crossmatch testing with K-negative RBCs a reasonable alternative when urgent transfusion is indicated.[9]

References

  1. World Health Organization (2009). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 101" (PDF). WHO Drug Information. 23 (2).
  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.
  3. "'Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab'". Janssen Biotech. Retrieved 2013-01-31.
  4. "ASCO: Drug Shows Promise in Myeloma". MedPage Today.
  5. "'Daratumumab Continues To Show Promise For Relapsed/Refractory Myeloma Patients (ASH 2012)'". The Myeloma Beacon. Retrieved 2013-01-31.
  6. http://www.medscape.com/viewarticle/854548?nlid=91686_3663&src=wnl_edit_newsal&uac=78316PX&impID=890536&faf=1
  7. http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100115/darzalex-daratumumab
  8. "Janssen's Single-Agent DARZALEX® (daratumumab) Approved by European Commission for Treatment of Multiple Myeloma (MM) | Business Wire". www.businesswire.com. Retrieved 2016-05-23.
  9. 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. doi:10.1111/trf.13069. PMID 25764134.
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