Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination

Vaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens is currently being tested as an adjuvant treatment modality for resected locoregional metastatic (stage III) melanoma. Based on its mechanism of action, DC vaccination might potentiate the clinical efficacy of concurrent or sequential immune checkpoint inhibition (ICI). The purpose of this study was to determine the efficacy of ICI administered following recurrent disease during, or after, adjuvant DC vaccination. To this end, we retrospectively analyzed clinical responses of 51 melanoma patients with either irresectable stage III or stage IV disease treated with first- or second-line ICI following recurrence on adjuvant DC vaccination. Patients were analyzed according to the form of ICI administered: PD-1 inhibition monotherapy (nivolumab or pembrolizumab), ipilimumab monotherapy or combined treatment with ipilimumab and nivolumab. Treatment with first- or second-line PD-1 inhibition monotherapy after recurrence on adjuvant DC vaccination resulted in a response rate of 52%. In patients treated with ipilimumab monotherapy and ipilimumab-nivolumab response rates were 35% and 75%, respectively. In conclusion, ICI is effective in melanoma patients with recurrent disease on adjuvant DC vaccination

Towards better immunotherapeutic management of cutaneous and uveal melanoma

Contains fulltext : 228319.pdf (publisher's version ) (Open Access)Radboud University, 14 januari 2021Promotores : Vries, I.J.M. de, Gerritsen, W.R. Co-promotores : Bol, K.F., Schreibelt, G.209 p

18F-FDG PET/CT of Multiorgan Sarcoid-Like Reaction During Anti-PD-1 Treatment for Melanoma

We report a case of a 50-year-old woman treated with anti-PD-1 inhibition for metastatic melanoma. During treatment, extensive and transient histopathologically confirmed sarcoid-like reaction was detected in multiple organ systems and at different time points using F-FDG PET/CT imaging. Immune-related adverse events during anti-PD-1/PD-L1 antibody treatment are increasingly being reported. This case report emphasizes the broad spectrum of possible presentations of sarcoid-like reaction detected by F-FDG PET/CT and its evolution in time. For the clinician, awareness of these immune-related adverse events helps to accurately interpret findings on imaging

Dendritic Cell Cancer Therapy: Vaccinating the Right Patient at the Right Time

Contains fulltext : 200038.pdf (publisher's version ) (Open Access)Immune checkpoint inhibitors propelled the field of oncology with clinical responses in many different tumor types. Superior overall survival over chemotherapy has been reported in various metastatic cancers. Furthermore, prolonged disease-free and overall survival have been reported in the adjuvant treatment of stage III melanoma. Unfortunately, a substantial portion of patients do not obtain a durable response. Therefore, additional strategies for the treatment of cancer are still warranted. One of the numerous options is dendritic cell vaccination, which employs the central role of dendritic cells in activating the innate and adaptive immune system. Over the years, dendritic cell vaccination was shown to be able to induce an immunologic response, to increase the number of tumor infiltrating lymphocytes and to provide overall survival benefit for at least a selection of patients in phase II studies. However, with the success of immune checkpoint inhibition in several malignancies and considering the plethora of other treatment modalities being developed, it is of utmost importance to delineate the position of dendritic cell therapy in the treatment landscape of cancer. In this review, we address some key questions regarding the integration of dendritic cell vaccination in future cancer treatment paradigms

Early Recurrence in Completely Resected IIIB and IIIC Melanoma Warrants Restaging Prior to Adjuvant Therapy

PURPOSE: To evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy. PATIENTS AND METHODS: One hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NCT02993315). All patients underwent imaging to exclude local relapse or metastasis before entering the trial. The frequency of recurrent disease within 12 weeks after resection and the method of detection were investigated. RESULTS: Sixty-nine (58%) stage IIIB and 51 (43%) stage IIIC melanoma patients were screened. Median age was 54 (range 27-79) years. Twenty-two (18%) of 120 patients with completely resected stage IIIB/C melanoma had evidence of early recurrent disease, despite exclusion thereof by prior imaging. Median interval between resection and detection of relapse was 7.4 (range 4.3-10.7) weeks. Recurrence was asymptomatic in 17 (77%) patients, but metastasis was noticed by the patient or physician in 5 (23%). Eight patients with local relapse received local treatment with curative intent, and one was treated with systemic therapy. The remaining patients had distant metastasis, 1 of whom underwent resection of a solitary liver metastasis while 12 patients received systemic treatment. CONCLUSIONS: Patients with completely resected stage IIIB/C melanoma have high risk of early recurrence before start of adjuvant therapy. Restaging should be considered for high-risk melanoma patients before start of adjuvant therapy

Health-related quality of life analysis in stage III melanoma patients treated with adjuvant dendritic cell therapy

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