title: Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma.
abstract: 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 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor 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 toward increased natural killer 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. Fifty percent 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. This trial was registered at www.clinicaltrials.gov as #NCT813320.
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gelfand
authors.forename: Joel C
authors.initials: JC
authors.lastname: Gelfand
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Maria
authors.initials: M
authors.lastname: Wysocka
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Troxel
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Bernice
authors.initials: B
authors.lastname: Benoit
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland; Department of Dermatology, University Hospital, Basel, Switzerland;
authors.forename: Christian
authors.initials: C
authors.lastname: Surber
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Rosalie
authors.initials: R
authors.lastname: Elenitsas
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Marie A
authors.initials: MA
authors.lastname: Buchanan
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Leahy
authors.affiliation: Department of Dermatology, University of Tokyo, Tokyo, Japan; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Adaptive Biotechnologies, Seattle, WA; and.
authors.forename: Ilan R
authors.initials: IR
authors.lastname: Kirsch
authors.affiliation: Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Dana-Farber/Brigham and Women's Cancer Center, Boston, MA.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; C402365:resiquimod