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Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma.

  • Rook AH Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Gelfand JM Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Gelfand JC Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Wysocka M Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Troxel AB Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Benoit B Department of Dermatology, University Hospital, Zürich, Switzerland; Department of Dermatology, University Hospital, Basel, Switzerland;
  • Surber C Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Elenitsas R Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Buchanan MA Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Leahy DS Department of Dermatology, University of Tokyo, Tokyo, Japan; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
  • Watanabe R Adaptive Biotechnologies, Seattle, WA; and.
  • Kirsch IR Department of Dermatology and the Center for Clinical Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
  • Kim EJ Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Dana-Farber/Brigham and Women's Cancer Center, Boston, MA.
  • Clark RA
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  • 2015-08-01
Published in:
  • Blood. - 2015
Administration, Topical
Adult
Aged
Antineoplastic Agents
Female
Humans
Imidazoles
Lymphoma, T-Cell, Cutaneous
Male
Middle Aged
Skin
Skin Neoplasms
T-Lymphocytes
English 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/41918
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