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Last Updated: 06/21/23

Success Story

Ontak (NSC 697979)

High-dose therapy, combined with a hematopoietic stem cell transplant, is usually the best treatment option for hematological cancers. However, stem cell transplants may lead to the development of graft-versus-host disease (GVHD), in which donor lymphocytes attack the patient’s healthy cells. Researchers from Boston recently found evidence that Ontak may prove an effective treatment for GVHD. This trial included 30 patients who had developed acute GVHD following an allogeneic stem cell transplant that had stopped responding to treatment with steroids. Following treatment with Ontak, half of the patients achieved a complete resolution of GVHD, and 21% achieved a partial resolution. Treatment with Ontak was generally well tolerated.3, 4


Ontak (NSC 697979), also known as denileukin diftitox or interleukin-2 (IL-2) fusion protein, is created by replacing the receptor-binding domain of diphtheria toxin with IL-2, whose receptor is overexpressed in leukemia cells. Thus, IL-2 carries the protein inhibitory function of diphtheria toxin to the targeted leukemia cells.

Ontak is one of four NCDDG-developed agents approved by the FDA since the inception of the NCDDG program.1 It was created by an NCDDG headed by Dr. John Murphy, of University Hospital in Boston, in collaboration with Seragen, Inc.1 Later, Ligand Pharmaceuticals, Inc., acquired the marketing rights for Ontak, which was approved by the FDA through its accelerated approval regulations in 1998.1

Although Ontak was approved for the treatment of cutaneous T-cell lymphoma, clinical trials are under way to assess its effectiveness in the treatment of relapsed or refractory non-Hodgkin lymphoma, advanced melanoma, and advanced kidney cancer.2 Studies of long-term safety and efficacy also are under way, as required for drugs approved through the accelerated approval process. In addition, Ontak is under development for chronic lymphocytic leukemia.

1 Developmental Therapeutics Program. Grants and Contracts Operations Branch (GCOB) Website.


3 Cancer Consultants. Ontak may be an effective treatment option for refractory graft-versus-host-disease.

4 Ho VT, Zahrieh D, Hochberg E, Micale E, Levin J, Reynolds C, Steckel S, Cutler C, Fisher DC, Lee SJ, Alyea EP, Ritz J, Soiffer RJ, Antin JH. Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 2004;104:1224–1226.


DTP NCDDG poster (pdf)