Investigational Topical Gel Is Safe and Effective in Patients With Cutaneous T-Cell Lymphoma, Phase I Trial Shows
Results of a phase I trial show that an investigational topical drug, resiquimod gel, causes regression of both treated and untreated tumor lesions and may completely remove cancerous cells from both sites in patients with early-stage cutaneous T-cell lymphoma. Currently, there is no cure for cutaneous T-cell lymphoma, aside from a bone marrow transplant. However, the new study from researchers at the Perelman School of Medicine at the University of Pennsylvania shows that the topical gel can eliminate malignant T cells, leading to diminished lesions. Results, which build upon previous research, are encouraging to patients who have not responded to other modalities, including certain types of topical chemotherapy, phototherapy, and even systemic treatment with interferon alpha and oral bexarotene. The study was published by Rook et al in Blood.
Trial Details
In the trial, co-led by Rachael Clark, MD, PhD, Associate Professor of Dermatology at Harvard Medical School; Alain Rook, MD, Professor of Dermatology and Director of the Cutaneous Lymphoma Program at Penn Medicine; and Joel M. Gelfand, MD, MSCE, Associate Professor of Dermatology and Medical Director of the Clinical Studies Unit at Penn Medicine; 12 patients who had previously undergone an average of six treatments for early-stage cutaneous T-cell lymphoma were treated with topical resiquimod gel at varying doses and intervals.
Patients applied specified doses (0.03%–0.06%) to select skin lesions for 16 weeks. However, some patients using the 0.06% dose showed a full clearing of all malignant cells after only 8 weeks.
Results
By the final evaluation, treated lesions were significantly improved in 75% of patients, and 30% saw full resolution in all treated lesions. Unlike other treatments, resiquimod also improved untreated lesions, resulting in more than 50% improvement for more than 90% of patients. Two participants, one of whom had been living with cutaneous T-cell lymphoma for more than 15 years without response to treatment, saw full eradication of the disease.
“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,” said Dr. Rook. “To our knowledge, this is the first topical therapy that can clear untreated lesions and lead to complete remission in some patients.”
Using a method known as high-throughput sequencing, the team was able 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 among 100,000 healthy cells.
DNA from biopsies of the same treated lesion was analyzed before treatment and 8 weeks after treatment began to identify the number of malignant T cells. The percentage of malignant T cells was reduced significantly in 9 of 10 tested participants. Of the 10 tested, 3 had complete eradication of the malignant population, and 1 had a 99.6% reduction.
“Overall, lesions responded far better to topical resiquimod than they have with other topical therapies, including some potent topical steroids and topical chemotherapy,” Dr. Rook said. “Building upon previous research, our study suggests resiquimod might be useful in combination with other therapies in the treatment of more advanced cutaneous T-cell lymphoma. Further research with larger participant populations is needed to determine the best approach and application for these patients.”
Dr. Clark is the corresponding author for the Blood article.
This study was funded by the National Institutes of Health and the Food and Drug Administration. Resiquimod for the trial was provided by Spirig, Inc. The authors disclosed no conflicts of interest.
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