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Antitumor activity of DAB389IL-2 fusion toxin in mycosis fungoides
M N Saleh1, C F LeMaistre, T M Kuzel
1The University of Alabama at Birmingham, USA.
Background:
DAB389IL-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 DAB389IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma.
Methods:
DAB389IL-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 microg/kg per day were well tolerated. Clinical responses were observed at all dose levels.
Conclusion:
DAB389IL-2 is well tolerated at doses of less than 31 microg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
Insights
DAB389IL-2, a novel fusion toxin, shows antitumor activity and is well tolerated in patients with cutaneous T-cell lymphoma. This therapy induced clinical responses in mycosis fungoides, even in previously treated patients.
Area of Science:
- Oncology
- Immunotherapy
- Drug Development
Background:
- DAB389IL-2 is a novel fusion toxin designed to target tumors expressing the interleukin-2 (IL-2) receptor.
- It utilizes the cytotoxic A-chain of diphtheria toxin for targeted tumor cell destruction.
Purpose of the Study:
- To evaluate the safety, maximum tolerated dose (MTD), and clinical efficacy of DAB389IL-2.
- The study focused on patients with lymphoproliferative malignancies, specifically cutaneous T-cell lymphoma (CTCL).
Main Methods:
- A phase I clinical trial was conducted with dose escalation.
- DAB389IL-2 was administered intravenously for 5 consecutive days every 3 weeks.
- Patients were monitored for toxicity, pharmacokinetics, immune response, and efficacy.
Main Results:
- Thirty-five CTCL patients, including 30 with mycosis fungoides, were treated; 34 had failed prior conventional therapies.
- Objective responses were observed in 13 patients (37%), with 5 (14%) achieving complete response, particularly those with extensive erythroderma and tumor-stage mycosis fungoides.
- Adverse events included reversible fever, chills, hypotension, nausea, vomiting, and elevated hepatic transaminases. Doses below 31 microg/kg/day were well tolerated.
Conclusions:
- DAB389IL-2 demonstrates good tolerability at doses under 31 microg/kg/day.
- The fusion toxin induced clinical responses in patients with mycosis fungoides, confirming its antitumor activity.