Topical resiquimod is a safe, effective therapy for early stage CTCL that can clear both treated and untreated skin lesions.
Responding patients had T cell recruitment into skin, enhanced T cell effector functions and eradication of the malignant T cell clone.
Early stage cutaneous T cell lymphoma (CTCL) is a skin limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase I trial of 0.03% and 0.06% topical resiquimod gel, a TLR7/TLR8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. 92% of patients had over a 50% improvement in body surface area involvement by mSWAT analysis and two patients experienced complete clearing of disease. Four of five patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. TCR sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T cell clones in treated skin, increased skin T cell effector functions, and a trend towards increased NK cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. 50% of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients.
- Submitted February 23, 2015.
- Accepted July 20, 2015.
- Copyright © 2015 American Society of Hematology