Sofie Wilgenhof1, Jurgen Corthals1, Carlo Heirman1, Nicolas van Baren1, Sophie Lucas1, Pia Kvistborg1, Kris Thielemans1, Bart Neyns2. 1. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 2. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands. Bart.Neyns@uzbrussel.be.
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.
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.
Authors: Stefanie Gross; Michael Erdmann; Ina Haendle; Steve Voland; Thomas Berger; Erwin Schultz; Erwin Strasser; Peter Dankerl; Rolf Janka; Stefan Schliep; Lucie Heinzerling; Karl Sotlar; Pierre Coulie; Gerold Schuler; Beatrice Schuler-Thurner Journal: JCI Insight Date: 2017-04-20
Authors: Hayley S Ma; Bibhav Poudel; Evanthia Roussos Torres; John-William Sidhom; Tara M Robinson; Brian Christmas; Blake Scott; Kayla Cruz; Skylar Woolman; Valerie Z Wall; Todd Armstrong; Elizabeth M Jaffee Journal: Cancer Immunol Res Date: 2019-01-14 Impact factor: 11.151