Dose Seeking Evaluation of a Novel Heterologous Primeboost Immunotherapy in Stage III and IV Metastatic Melanoma Patients

2004 ◽  
Vol 27 (6) ◽  
pp. S27
Author(s):  
Frank Malinoski ◽  
Robert Hawkins ◽  
Christian Ottensmeier ◽  
John Smyth ◽  
Adrian Harris ◽  
...  
2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 2570-2570 ◽  
Author(s):  
R. E. Hawkins ◽  
U. Keilholz ◽  
A. Dangoor ◽  
A. Harris ◽  
C. Ottensmeier ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
R. E. Hawkins ◽  
A. Dangoor ◽  
U. Keilholz ◽  
D. Schadendorf ◽  
A. Harris ◽  
...  

8030 Background: This trialevaluated the safety, immunogenicity and tumour response of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3), containing 7 melanoma epitopes. Methods: 41 HLA-A2 positive stage III/IV melanoma patients with unresectable measurable disease were enrolled. Immunisations were administered three weeks apart with continued MVA.Mel3 boosting in patients with tumour control. Epitope-specific CD8+ T cell responses were evaluated using ex vivo tetramer staining and interferon gamma (IFN-γ) ELISPOT assay. Results: DNA.Mel3 was well tolerated at all doses. Dose-related grade 3 local skin reactions and systemic immune-associated reactions were observed following MVA.Mel3, no reactions led to early study discontinuation. Melan-A tetramer responses were observed in 23/36 (64%) evaluable patients, of which 9/36 showed an IFNγ response to at least one epitope in ELISPOT assay. Seven patients (17%) showed tumour control (PR, MR, or SD >6 months), of which 3/7 patients had associated immune responses, including one with PR > 21 months who underwent extended MVA.Mel3 boosting. Overall median progression free survival was 9 weeks (16 weeks for immune responders). Median overall survival for the intention-to-treat population is 11.7 months with follow up of 16 patients continuing. Conclusions: High dose heterologous PrimeBoost immunisation was safe and stimulated immune responses in >50% of late stage metastatic melanoma patients treated. Tumour control was observed with some evidence of association with immune response. [Table: see text] [Table: see text]


2014 ◽  
Vol 2 (7) ◽  
pp. 668-678 ◽  
Author(s):  
Benjamin Weide ◽  
Thomas K. Eigentler ◽  
Annette Pflugfelder ◽  
Henning Zelba ◽  
Alexander Martens ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9593-9593
Author(s):  
Viola Franke ◽  
Max Fullah Madu ◽  
Carolien Bierman ◽  
Willem M.C. Klop ◽  
Winan J. van Houdt ◽  
...  

9593 Background: With the approval of adjuvant therapy for stage III melanoma, accurate staging in melanoma patients is important more than ever to prevent over- or undertreatment. Sentinel node biopsy (SNB) is an accurate staging tool, yet the presence of capsular nevi (CN) can lead to a false positive diagnosis. We compared positive SNB and CN patient outcomes and aimed to evaluate the cause of false positive SNB and discern diagnostic pitfalls in their evaluation. Methods: Retrospective analysis of AJCC 7th Edition stage IIIA melanoma patients (N1-2a, non-ulcerated primary tumor) who were treated at our institute between 2000 and 2015. SNB slides were reviewed for this study by an expert melanoma pathologist. Baseline characteristics were assessed for SN+ and CN+ patients. Concordance rates for SNB evaluation before and after revision were documented and diagnostic pitfalls were discerned. Results: 169 patients were diagnosed, 10 could not be reviewed due to lack of evaluable slides. Of these 159 cases, 14 patients originally diagnosed with metastatic melanoma were shown to have capsular nevi (8.8%). Another 2 patients were shown to have melanophages that were incorrectly interpreted as metastases (1.3%). Thus, 10.1% was considered false positive after revision. In 14 patients the SN tumor burden was originally reported > 1 mm, but turned out to have < 1 mm SN tumor burden. 4 patients originally reported as SN tumor burden < 1 mm before revision turned out to have > 1 mm SN tumor burden. These 32 patients (20%) might have potentially been over- or undertreated in the current era of adjuvant therapy for stage III melanoma. Conclusions: False positive sentinel node results in melanoma are real, they can occur for a number of reasons, but distinguishing metastatic melanoma from benign capsular nevi and melanophages can be a diagnostic challenge. We plead for an expert pathologists’ review in any case, but certainly when using the SNB+ results to determine treatment consequences for SN+ melanoma patients.


2013 ◽  
Vol 2 (9) ◽  
pp. e25564 ◽  
Author(s):  
Hojabr Kakavand ◽  
Richard A Scolyer ◽  
John F Thompson ◽  
Graham J Mann

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 9041-9041 ◽  
Author(s):  
Dario Neri ◽  
Benjamin Weide ◽  
Thomas K. Eigentler ◽  
Annette Pflugfelder ◽  
Henning Zelba ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3361
Author(s):  
Matias A. Bustos ◽  
Rebecca Gross ◽  
Negin Rahimzadeh ◽  
Hunter Cole ◽  
Linh T. Tran ◽  
...  

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients’ disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients’ responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients’ and 73 normal donors’ plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors’ plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII.


Sign in / Sign up

Export Citation Format

Share Document