Find an Immunologist
Login
Donate
Menu
News
Latest News
CIS Statement on Supreme Court Decision
Journal of Clinical Immunology (JoCI) Update
Baltimore Wine Festival
Endorsement of IPOPI Advocacy Statement on PIDs and Disability Support
Statement on SCIG and IVIG
COVID-19 Resources
Resources
Find an Immunologist
Job Board
Webinars
Listserv
WEBbook of Biologic Therapies
Speakers Bureau
Video Library
DLI Lab Directory
Funding/Grants
Advocacy
Related Organizations
Meetings
2023 Annual Meeting
2023 Diagnostic School
2023 CIS/Grifols AIM Program
2023 Summer School
CIS Meeting Attendee Code of Conduct
Policy on Posting Outside Meeting Advertisments
Related Meetings
Membership
Members Only
Membership Categories
Member Benefits
Become a Member
Renew My Membership
Early Career Immunologists
Membership Code of Conduct
About
Get Involved
Leadership
Bylaws
Committees and Task Forces
Strategic Plan
Foundation
IAPIDS
Awards
ACCME Accreditation
Contact Us
Find an Immunologist
Login
Donate
WEBbook of Biologic Therapies
>
Detail
Email
Print
Denileukin diftitox
Return to Listing
Compound Name:
Denileukin diftitox
Molecular Target:
IL-2 Receptor
Molecular Structure:
recombinant fusion protein expressing amino acid residues of diphtheria toxin fragment A & B, followed by the sequence for IL-2
Licensed Indication:
recurrent CD25 positive, cutaneous T-cell lymphoma
Manufacturer and/or Distributor:
Eisai
Initial FDA Approval:
1999
Summary:
Denileukin diftitox (Ontak) is a recombinant DNA-derived cytotoxic protein composed of the active domains of diphtheria toxin (fragments A and B) fused to human interleukin-2. After binding to the IL-2 receptor on the cell surface, denileukin diftitox is internalized by receptor-mediated endocytosis. The fusion protein is subsequently cleaved, which releases the diphtheria toxin enzymatic and translocation domains from the IL-2 fragment. The toxin then inhibits protein synthesis and causes cell death. Deniluekin difitox is administered intravenously in 5 day cycles every 3 weeks.

 In 1999, the FDA approved the use of this drug for treatment of persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.

 The most common adverse reactions (≥20%) are pyrexia, nausea, fatigue, rigors, vomiting, diarrhea, headache, peripheral edema, cough, dyspnea and pruritus. Three serious potential adverse reactions are of particular concern: 1) infusion reactions during the 24 hours after infusion; 2) capillary leak syndrome, which was defined as the occurrence of at least 2 of 3 key symptoms (hypotension, edema, serum albumin <3.0 g/dL) at any time during Ontak therapy; 3) loss of visual acuity, usually with loss of color vision, with or without retinal pigment mottling.
References
Package Insert
Prince HM, Duvic M, Martin A, Sterry W, Assaf C, Sun Y, et al. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2010 Apr 10;28(11):1870-1877.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20212249
Park M, Liu GT, Piltz-Seymour J, Wisda CL, Rook AH, Junkins-Hopkins JM, et al. Vision loss following denileukin diftitox treatment: a case report of possible posterior ischemic optic neuropathy. Leuk Lymphoma. 2007 Apr;48(4):808-811.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17454642
Manoukian G, Hagemeister F. Denileukin diftitox: a novel immunotoxin. Expert Opin Biol Ther. 2009 Nov;9(11):1445-1451.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19817678
Turturro F. Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther. 2007 Jan;7(1):11-17.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17187516
Olsen E, Duvic M, Frankel A, Kim Y, Martin A, Vonderheid E, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2001 Jan 15;19(2):376-388.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11208829
Foss FM, Zinzani PL, Vose JM, Gascoyne RD, Rosen ST, Tobinai K. Peripheral T-cell lymphoma. Blood. 2011 Jun 23;117(25):6756-6767.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21493798
Coiffier B, Federico M, Caballero D, Dearden C, Morschhauser F et al. Therapeutic options in relapsed or refractory peripheral T-cell lymphoma. Cancer Treat Rev. 2014 Oct;40(9):1080-8.
http://www.ncbi.nlm.nih.gov/pubmed/25199959
Gooptu M, Rhoades R, Pro B. Current management of peripheral T-cell lymphomas. Cancer Treat Res. 2015;165:289-303.
http://www.ncbi.nlm.nih.gov/pubmed/25655615
Nomenclature
top