Denileukin Diftitox as Novel Targeted Therapy in Non-Hodgkin's Lymphoma

Abstract

Non-Hodgkin's lymphoma (NHL) is a complex group of hematologic malignancies. The majority are B-cell lineage, with 10%-20% arising from T-cell lineage. Detailed knowledge of the subtypes and staging of NHL is essential to plan treatment and provide effective management of treatment-related side effects. Although numerous regimens have demonstrated efficacy in the treatment of NHL, some subtypes of lymphomas generally are not curable. The recent development of targeted therapies such as denileukin diftitox (Ontak, Ligand Pharmaceuticals, Inc., San Diego, CA) has resulted in potentially significant advances in the treatment of NHL. Oncology nurses must gain a better understanding of the unique mechanism of action of this agent and its side effects to successfully manage patients being treated with this novel therapy.

Thyrotoxicosis after Denileukin Diftitox Therapy in Patients with Mycosis Fungoides

“…Denileukin diftitox (DAB 389 IL-2, ONTAK, Ligand Pharmaceuticals Inc., San Diego, CA) is a novel fusion toxin consisting of the enzymatic and translocating domain of diphtheria toxin (amino acids 1-389) and the ligand-binding domain of recombinant human IL-2 (1). The potential for denileukin diftitox to bind selectively to high-affinity (CD25/CD122/ CD132) IL-2 receptors, generally expressed only on activated T and B lymphocytes and macrophages (2,3), provided the rationale for its use in cutaneous T cell lymphomas (CTCLs) (4 -6) and non-Hodgkin's lymphomas (7,8). Denileukin diftitox has also been used in psoriasis (9), graft-vs.-host disease (10,11), chronic lymphocytic leukemia (12), and for targeting T-regulatory cells in solid tumors (7,8,13).…”

Adverse Effects of Denileukin Diftitox and Their Management in Patients With Cutaneous T-Cell Lymphoma

“…Fever typically develops 48-72 hours after DD administration. A complete blood count with differential, blood and urine cultures, and a chest X-ray in patients with a temperature exceeding 101ºF would be the next steps in determining a differential diagnosis, because infection is not an uncommon complication in patients with CTCL (Walker & Dang, 2004).…”

“…If transaminase levels are found to be elevated by liver function testing conducted prior to a course of DD, treatment should be held and the decision of when to resume DD is left to the discretion of the healthcare provider. A conservative approach is to delay DD administration until transaminase levels return to grade 1 (i.e., 2.5 times or less the upper limit of normal) or lower (Dang et al, 2004;Walker & Dang, 2004).…”