1. Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.
- Author
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Wilgenhof S, Corthals J, Heirman C, van Baren N, Lucas S, Kvistborg P, Thielemans K, and Neyns B
- Subjects
- Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Cells, Cultured, Chemotherapy, Adjuvant, Dendritic Cells immunology, Dendritic Cells metabolism, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, Genetic Therapy adverse effects, Genetic Therapy mortality, Humans, Ipilimumab, Kaplan-Meier Estimate, Male, Melanoma genetics, Melanoma immunology, Melanoma mortality, Middle Aged, Proportional Hazards Models, RNA, Messenger metabolism, Skin Neoplasms genetics, Skin Neoplasms immunology, Skin Neoplasms mortality, Time Factors, Transplantation, Autologous, Treatment Outcome, Young Adult, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Dendritic Cells transplantation, Electroporation, Genetic Therapy methods, Melanoma therapy, RNA, Messenger genetics, Skin Neoplasms therapy
- Abstract
Purpose: Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma., Patients and Methods: Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point., Results: The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event., Conclusion: The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma., (© 2016 by American Society of Clinical Oncology.)
- Published
- 2016
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