Immunological responses to adjuvant vaccination with combined CD1c+ myeloid and plasmacytoid dendritic cells in stage III melanoma patients

PURPOSE To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.

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Abstract 3412: 36-months and 18-months relapse-free survival after (neo)adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma patients - update of the OpACIN and OpACIN-neo trials

10.1158/1538-7445.am2020-3412 ◽

2020 ◽

Cited By ~ 1

Author(s):

Christian U. Blank ◽

Judith M. Versluis ◽

Elisa A. Rozeman ◽

Alexander M. Menzies ◽

Irene L. Reijers ◽

...

Keyword(s):

Stage Iii ◽

Relapse Free Survival ◽

Free Survival ◽

Melanoma Patients ◽

Stage Iii Melanoma

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Therapeutic efficacy of melanoma-reactive TIL injected in stage III melanoma patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-002-0313-3 ◽

2002 ◽

Vol 51 (10) ◽

pp. 532-538 ◽

Cited By ~ 52

Author(s):

Nathalie Labarrière ◽

Marie-Christine Pandolfino ◽

Nadine Gervois ◽

Amir Khammari ◽

Marie-Hélène Tessier ◽

...

Keyword(s):

Therapeutic Efficacy ◽

Stage Iii ◽

Melanoma Patients ◽

Stage Iii Melanoma

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HLA-A*0201 + Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients

Journal of Investigative Dermatology ◽

10.1038/jid.2012.152 ◽

2012 ◽

Vol 132 (10) ◽

pp. 2395-2406 ◽

Cited By ~ 17

Author(s):

Caroline Aspord ◽

Marie-Therese Leccia ◽

Dimitri Salameire ◽

David Laurin ◽

Laurence Chaperot ◽

...

Keyword(s):

Dendritic Cells ◽

Plasmacytoid Dendritic Cells ◽

A Cell ◽

Melanoma Patients

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Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients

Pigment Cell & Melanoma Research ◽

10.1111/pcmr.12290 ◽

2014 ◽

Vol 27 (6) ◽

pp. 1106-1116 ◽

Cited By ~ 10

Author(s):

Swetlana Mactier ◽

Kimberley L. Kaufman ◽

Penghao Wang ◽

Ben Crossett ◽

Gulietta M. Pupo ◽

...

Keyword(s):

Stage Iii ◽

Survival Outcomes ◽

Ajcc Stage ◽

Protein Signatures ◽

Melanoma Patients ◽

Stage Iii Melanoma

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Predicting clinical outcome through gene expression profiling in stage III melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8502 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8502-8502

Author(s):

T. John ◽

M. A. Black ◽

T. Toro ◽

C. A. Gedye ◽

I. D. Davis ◽

...

Keyword(s):

Gene Expression ◽

Clinical Outcome ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Stage Iiib ◽

Stage Iii ◽

Test Set ◽

Prognostic Groups ◽

Melanoma Patients ◽

Stage Iii Melanoma

8502 Background: Melanoma patients with clinically involved regional lymph nodes (Stage IIIB&C) represent a prognostically heterogeneous population. Current prognostic factors cannot distinguish the 30% of patients who will achieve long term survival from those who will relapse early. We hypothesized that gene expression profiling could identify these different prognostic groups and provide a greater understanding of the genetic mechanisms involved. Methods: Lymph node sections from 29 patients with Stage IIIB & IIIC melanoma and divergent clinical outcome as defined by time to tumor progression (TTP), including 16 poor (TTP<6 months) and 13 good (TTP>28 months) prognosis patients, were subjected to molecular profiling using spotted oligonucleotide arrays containing 30,888 probes as an initial test set. The differentially expressed genes were determined using a Wilcoxon-Mann-Whitney t-test with the false discovery rate controlling method of Benjamini-Hochberg and validated using quantitative real-time RT-PCR. Using logistic regression, a predictive score algorithm was developed based on the 15 genes for which the correlation between the two platforms was the strongest. The score was then applied to two independent validation sets of 10 and 14 patient samples. Results: Supervised analysis using differentially expressed genes was able to distinguish the two prognostic groups in the test set. The score correlated directly with clinical outcome, with higher scores associated with improved TTP. When the score was then applied to two independent sets of Stage III melanoma patient samples, it predicted clinical outcome accurately in 90% of samples. Conclusions: Stage IIIB and IIIC melanoma can be prognostically sub-classified according to the expression of 15 genes. To our knowledge this is the first study focused on Stage III disease using ex vivo patient samples. These results are encouraging and this genetic signature is currently being validated on a larger cohort. This method will allow appropriate stratification of stage III melanoma patients in adjuvant clinical trials, ameliorating the inherent biological heterogeneity that can confound these studies. [Table: see text]

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