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The science and practice of human immunology

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The science and practice of human immunology

Ofatumumab

Summary

Ofatumumab (Arzerra) is a human IgG1k monoclonal antibody directed to the B-cell surface antigen CD20.  Ofatumumab binds to both the small and large extracellular loops of the CD20 molecule, which is an epitope specificity different from that of rituximab and most other CD20 directed antibodies. It appears to promote more effective complement deposition and ADCC.  Ofatumumab received accelerated approval from the FDA in 2006 for treating chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab.  Its use in other conditions treated by rituximab is not yet established.

The major safety concerns are infusion reactions, cytopenias, hepatitis B, and progressive multifocal leukoencephalopathy (PML).

Brand name

Arzerra

Other names

HuMax-CD20

Molecular target

CD20

Molecular structure

Human IgG1k monoclonal antibody, recombinant

Licensed indication

Chronic lymphocytic leukemia resistant to fludarabine and alemtuzumab

Manufacturer/Distributor

Glaxo Smith Kline

Initial FDA Approval

2009

References

Package Insert: http://us.gsk.com/products/assets/us_arzerra.pdf

1.    Beum PV, Lindorfer MA, Beurskens F, Stukenberg PT, Lokhorst HM, Pawluczkowycz AW, et al. Complement activation on B lymphocytes opsonized with rituximab or ofatumumab produces substantial changes in membrane structure preceding cell lysis. J Immunol. 2008 Jul 1;181(1):822-832.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18566448
2.    Gravanis I, Ersboll J, Skovlund E, Abadie E, Marty M, Pignatti F. The European Medicines Agency review of ofatumumab (Arzerra(R)) for the treatment of chronic lymphocytic leukemia in patients refractory to fludarabine and alemtuzumab: summary of the scientific assessment of the European medicines agency committee for medicinal products for human use. Oncologist. 2010;15(12):1335-1343.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21156732
3.    Keating MJ, Dritselis A, Yasothan U, Kirkpatrick P. Ofatumumab. Nat Rev Drug Discov. 2010 Feb;9(2):101-102.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20118960
4.    Lemery SJ, Zhang J, Rothmann MD, Yang J, Earp J, Zhao H, et al. U.S. Food and Drug Administration approval: ofatumumab for the treatment of patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. Clin Cancer Res. 2010 Sep 1;16(17):4331-4338.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20601446
5.    Wierda WG, Padmanabhan S, Chan GW, Gupta IV, Lisby S, Osterborg A. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood. 2011 Nov 10;118(19):5126-5129.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21856867
6.    Veliz M, Pinilla-Ibarz J. Role of ofatumumab in treatment of chronic lymphocytic leukemia. J Blood Med. 2011;2:71-77.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22287865
7.    Bauer K, Rancea M, Roloff V, Elter T, Hallek M, Engert A, et al. Rituximab, ofatumumab and other monoclonal anti-CD20 antibodies for chronic lymphocytic leukaemia. The Cochrane database of systematic reviews. 2012;11
http://dx.doi.org/10.1002/14651858.CD008079.pub2
 

Last updated: October 30, 2013