Antitumor activity of DAB389 IL-2 fusion toxin in mycosis fungoides

Authors

Mansoor Saleh, Aga Khan UniversityFollow
C. F. LeMaistre, University of Alabama at Birmingham, USA
Timothy Kuzel, University of Alabama at Birmingham, USA
Francine Foss, University of Alabama at Birmingham, USA
Leonidas Platanias, University of Alabama at Birmingham, USA
Gary Schwartz, University of Alabama at Birmingham, USA
Mark Ratain, University of Alabama at Birmingham, USA
Alain Rook, University of Alabama at Birmingham, USA
Cesar Freytes, University of Alabama at Birmingham, USA

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: DAB389 IL-2 is a novel fusion toxin that retargets the cytotoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor–expressing tumors. Objective: The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of DAB389 IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma.

Methods: DAB389 IL-2 was administered intravenously daily for 5 days every 3 weeks. Dose escalation occurred between patient groups. Patients were monitored for laboratory and clinical toxicity, kinetics, immune response, and clinical efficacy.

Results: Thirty-five patients with cutaneous T-cell lymphoma (including 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete response in five patients (14%). Complete response was achieved in patients with extensive erythroderma and tumor stage mycosis fungoides. Adverse events consisted of reversible fever/chills, hypotension, nausea/vomiting, and elevation of hepatic transaminase. Doses of less than 31 μg/kg per day were well tolerated. Clinical responses were observed at all dose levels.

Conclusion: DAB389 IL-2 is well tolerated at doses of less than 31 μg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule. (J Am Acad Dermatol 1998;39:63-73.)

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of the American Academy of Dermatology

DOI

https://doi.org/10.1016/S0190-9622(98)70403-7

Recommended Citation

Saleh, M., LeMaistre, C. F., Kuzel, T., Foss, F., Platanias, L., Schwartz, G., Ratain, M., Rook, A., Freytes, C. (1998). Antitumor activity of DAB389 IL-2 fusion toxin in mycosis fungoides. Journal of the American Academy of Dermatology, 39(1), 67-73.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/114