Biologic correlates of response and survival in patients with cutaneous T-cell lymphoma treated with denileukin diftitox

Clin Lymphoma Myeloma. 2006 Nov;7(3):199-204. doi: 10.3816/CLM.2006.n.059.

Abstract

Background: Denileukin diftitox, a fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domains of diphtheria toxin and human interleukin, resulted in a response rate of 30% in the phase III registration trial in patients with recurrent or persistent cutaneous T-cell lymphoma (CTCL). Little is known with regard to the biologic correlates of response or the impact of denileukin diftitox on disease progression and survival.

Patients and methods: In our single-center series of 37 patients with early- and advanced-stage disease with CTCL treated with denileukin diftitox at a dose of 9 microg/kg or 18 microg/kg per day, we observed an overall response rate of 51%.

Results: In 8 patients with early-stage (< IIA) CTCL, there were 5 responses (62.5%), and the median survival has not been reached, with 70% of patients still alive at 46 months. In 29 patients with advanced-stage (>/= IIB) disease, there were 14 responses (49.3%), and the median survival was 31 months. Changes in the number of CD4+ CD25+ T-cell populations were observed in 7 of 19 responders, with no overall changes in the absolute lymphocyte counts during the course of therapy. Decrease in lactate dehydrogenase was strongly correlated with clinical response (P < 0.05).

Conclusion: Denilekin diftitox was a well-tolerated treatment in early- and advanced-stage CTCL and was not associated with detrimental immunologic efects on lymphocyte populations.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / metabolism
  • Clinical Trials as Topic
  • Diphtheria Toxin / therapeutic use*
  • Female
  • Humans
  • Interleukin-2 / therapeutic use*
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Lymphoma, T-Cell, Cutaneous / drug therapy*
  • Lymphoma, T-Cell, Cutaneous / mortality*
  • Male
  • Middle Aged
  • Mycosis Fungoides / etiology
  • Mycosis Fungoides / pathology
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Fusion Proteins / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Diphtheria Toxin
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • denileukin diftitox