Dendritic cell vaccination in metastatic uveal melanoma as compassionate treatment: Immunological and clinical responses.

• DOI: 10.1200/jco.2019.37.15_suppl.e21024
• Publication Date: 2019-05-27T16:13:30Z
• Authors: Alvaro Moreira; Stefanie Gross; Ugur Uslu; Jan Doerrie; Mirko Kummer; Stefan Schliep; Felix Sponagl; Christopher Lischer; Michael Erdmann; Lucie Heinzerling; Gerold Schuler; Beatrice Schuler-...
• Keywords: GNAQ; Immune checkpoint

e21024 Background: Other than cutaneous melanoma, metastatic uveal melanoma (UM) is minimally responsive to checkpoint inhibitors. The prognosis remains very poor with mortality rates nearly unchanged over the last decades. recently growing insight that immunotherapy significantly improves outcomes for cancer patients led a re-emergence of vaccines including dendritic cell (DC) vaccines. Methods: We vaccinated an UM patient in compassionate use setting and assessed immunological clinical responses. Based on this experience we performed individual treatments other using DC loaded by peptide pulsing and/or mRNA transfection (autologous tumor RNA or coding antigens). Results: first was 2013 after liver metastasis resected blockade ipilimumab started. In 2014 showed progression liver. continued vaccination shorter intervals adapted antigen loading (with GNAQ driver mutation) accompanied further cycle ipilimumab. Therapy resulted complete remission metastases, but developed new skin metastases. Again (peptides passenger mutations predicted Next-Generation Sequencing) infusions pembrolizumab were Pathology from some regressing lesions massive T infiltration parallel mutation-specific cells could be found patient’s blood. Skin metastases regressed now free detectable 65 months. Immune monitoring blood vaccine-induced functional response against QNAQ-driver mutation. Three four are also still alive, one under combination pembrolizumab, two them showing measurable disease, deceased disease related 28 months, resulting median OS five 36.4 those CD4+ CD8+ INF-gamma autologous vaccine. No grade 3 4 toxicity occurred. Conclusions: observed prolonged fact 2/5 remain disease-free definitely encouraging. Vaccination antigen-laden potential therapeutic option melanoma. Combinations inhibitors proved promising, should evaluated trials.