Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

• Published in: BMC cancer Vol. 11; no. 1; p. 515
• Main Authors: Telang, Sucheta, Rasku, Mary Ann, Clem, Amy L, Carter, Karen, Klarer, Alden C, Badger, Wesley R, Milam, Rebecca A, Rai, Shesh N, Pan, Jianmin, Gragg, Hana, Clem, Brian F, McMasters, Kelly M, Miller, Donald M, Chesney, Jason
• Format: Journal Article
• Language: English
• Published: London BioMed Central 13.12.2011; BioMed Central Ltd; BMC
• Subjects: Aged; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Care and treatment; Clinical oncology; Clinical trials; Colleges & universities; Data collection; Development and progression; Diphtheria Toxin - therapeutic use; Drug dosages; Female; Health Promotion and Disease Prevention; Human subjects; Humans; Immunotherapy; Interleukin-2 - therapeutic use; Kentucky; Lymphocytes; Male; Medicine; Medicine/Public Health; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Oncology; Oncology, Experimental; Patient outcomes; Positron-Emission Tomography; Recombinant Fusion Proteins - therapeutic use; Research Article; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Surgical Oncology; Survival Analysis; T-Lymphocytes; Tomography, X-Ray Computed; Kentucky; Vitiligo; Melanoma Patient; Ipilimumab; Melanoma; Treg Cell
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-11-515

Background We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4 + CD25 HI Foxp3 + regulatory T cells and expanded melanoma-specific CD8 + T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients. Methods In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[ 18 F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging. Results After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year. Conclusions These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma. Trial registration NCT00299689