denileukin diftitox (Ontak, Lymphir)

Introduction

Tradenames: Ontak, Lymphir.

Cytotoxic recombinant protein consisting of diphtheria toxin combined with fragments of human interleukin-2 (IL-2).

Indications

• FDA approved for treatment of patients with persistent or recurrent CD25 positive cutaneous T-cell lymphoma
  • relapsed/refractory cutaneous T-cell lymphoma
• B-cell lymphoma (in clinical trials)
• Hodgkin's disease (in clinical trials)

Dosage

• 9-18 ug/kg/day
• 6 cycles of treatment (4 months)

Monitor

• testing for CD25 antigen
• complete blood count (CBC) weekly
• chemistry panel including:
  • renal function tests
  • liver function tests
  • serum albumin

Adverse effects

• 21% of patients require hospitalization due to adverse effects
• fever
• vascular leak syndrome
  • pre-existing cardiovascular disorder & low serum albumin predispose
• gastrointestinal toxicity
• acute hypersensitivity (69%)
• flu-like syndrome (91%)
• infection (48%)
• loss of visual acuity
  • usually with loss of color vision
  • persistent visual impairment

Mechanism of action

• binds to activated lymphocytes & macrophages
• may compromise immune function

More general terms

• recombinant protein; chimer
• antineoplastic immunomodulator