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A Phase I trial shows promising results for resiquimod gel in resolving lesions from cutaneous T-cell lymphoma (CTCL).

Figure. Resiquimods ... - Click to enlarge in new windowFigure. Resiquimod's systemic effect significantly reduced even lesions that did not directly receive treatment.

As reported in an article online ahead of print in Blood (, the treatment caused disease regression, eradicated malignant T cells, and enhanced T cell effector function in 12 patients with stages IA to IIA disease.


The authors, from the Perelman School of Medicine at the University of Pennsylvania, said that as far as they know this is the first topical therapy that can induce such clearance of CTCL lesions and lead to complete remission in some patients. Currently there is no cure for CTCL other than a bone marrow transplant.


"The results of the trial suggest that resiquimod is safely and effectively absorbed into the skin, and beyond diminishing treated lesions, also enhances the immune response, leading to healing of even untreated lesions," the first author and principal investigator, Alain H. Rook, MD, Professor of Dermatology and Director of the Cutaneous Lymphoma Program at Penn Medicine, said in a news release.


Using resiquimod on some CTCL lesions has a systemic effect, which can be seen in significantly diminished lesions that did not directly receive treatment, he said.


The patients, who had previously undergone an average of six treatments for early-stage CTCL, were treated with topical resiquimod gel at varying doses and intervals. Patients applied specified doses (0.03 to 0.06 percent) to select skin lesions for 16 weeks. Some patients using the 0.06 percent dose, however, showed a full clearing of all malignant cells after only eight weeks.


By the final evaluation, treated lesions were significantly improved in 75 percent of patients, and 30 percent saw full resolution in all treated lesions. Unlike other treatments, resiquimod also improved untreated lesions, resulting in more than 50 percent improvement for more than 90 percent of patients. Two participants, one of whom had CTCL for more than 15 years without any response to treatment, had full eradication of the disease, the team reported.


High-Throughput Sequencing

The researchers used high throughput sequencing to determine how many distinct malignant cells were present within a sample of healthy cells. The technique showed it could identify a single malignant cell amongst 100,000 healthy cells.


DNA from biopsies of the same treated lesion were analyzed before treatment and eight weeks later to determine the number of malignant T cells. The percentage of malignant T cells were reduced significantly in nine of 10 tested participants, three of whom had complete eradication of the malignant population, and one who had a 99.6 percent reduction.


"Overall, lesions responded far better to topical resiquimod than they have with other topical therapies, including some potent topical steroids and topical chemotherapy, and it was extremely well tolerated by patients," Rook said.


"Building upon previous research, our study suggests that resiquimod might be useful in combination with other therapies in the treatment of more advanced CTCL.


"Further research with larger participant populations is needed to determine the best approach and application for these patients."


Rook's co-leaders for the study were Rachael Clark, MD, PhD, Associate Professor of Dermatology at Harvard Medical School, and Joel M. Gelfand, MD, MSCE, Associate Professor of Dermatology and Medical Director of the Clinical Studies Unit at Penn Medicine. The other coauthors were Maria Wysocka, Andrea Troxel, Bernice Benoit, Christian Surber, Rosalie Elenitsas, Marie Buchanan, Deborah Leahy, Rei Watanabe, Ilan Kirsch, and Ellen Kim.


Funding for the study was provided by the National Institutes of Health and the Food and Drug Administration, and the product was supplied by the manufacturer, Spirig, Inc.