Abstract 2306: Treatment with hTERT/survivin mRNA-loaded dendritic cells combined with autologousex vivoexpanded T cells improves progression free survival in stage IV melanoma patients when compared to dendritic cell vaccines alone

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

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Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate

Cancer Immunology Immunotherapy ◽

10.1007/s00262-003-0495-3 ◽

2004 ◽

Vol 53 (7) ◽

pp. 651-658 ◽

Cited By ~ 40

Author(s):

R. Vilella ◽

D. Ben�tez ◽

J. Mil� ◽

M. Lozano ◽

R. Vilana ◽

...

Keyword(s):

Dendritic Cells ◽

Pilot Study ◽

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Stage Iv ◽

Melanoma Patients ◽

Stage Iv Melanoma

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CTLA4 promoter methylation predicts response and progression-free survival in stage IV melanoma treated with anti-CTLA-4 immunotherapy (ipilimumab)

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02777-4 ◽

2020 ◽

Author(s):

Simon Fietz ◽

Romina Zarbl ◽

Dennis Niebel ◽

Christian Posch ◽

Peter Brossart ◽

...

Keyword(s):

Protein Expression ◽

Promoter Methylation ◽

Single Agent ◽

Stage Iv ◽

Predictive Biomarkers ◽

Progression Free Survival ◽

Immune Checkpoint Blockade ◽

Response To Treatment ◽

Free Survival ◽

Stage Iv Melanoma

AbstractAnti-CTLA-4-antibodies can induce long-lasting tumor remissions. However, only a few patients respond, necessitating the development of predictive companion biomarkers. Increasing evidence suggests a major role of epigenetics, including DNA methylation, in immunology and resistance to immune checkpoint blockade. Here, we tested CTLA4 promoter methylation and CTLA-4 protein expression as predictive biomarkers for response to anti-CTLA-4 immunotherapy. We identified retrospectively N = 30 stage IV melanoma patients treated with single-agent anti-CTLA-4 immunotherapy (ipilimumab). We used quantitative methylation-specific PCR and immunohistochemistry to quantify CTLA4 methylation and protein expression in pre-treatment samples. CTLA4 methylation was significantly higher in progressive as compared to responding tumors and significantly associated with progression-free survival. A subset of infiltrating lymphocytes and tumor cells highly expressed CTLA-4. However, CTLA-4 protein expression did not predict response to treatment. We conclude that CTLA4 methylation is a predictive biomarker for response to anti-CTLA-4 immunotherapy.

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Pretreatment Levels of Peripheral Neutrophils and Leukocytes As Independent Predictors of Overall Survival in Patients With American Joint Committee on Cancer Stage IV Melanoma: Results of the EORTC 18951 Biochemotherapy Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.0274 ◽

2007 ◽

Vol 25 (12) ◽

pp. 1562-1569 ◽

Cited By ~ 136

Author(s):

Henrik Schmidt ◽

Stefan Suciu ◽

Cornelis J.A. Punt ◽

Martin Gore ◽

Wim Kruit ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Interleukin 2 ◽

Stage Iv ◽

Progression Free Survival ◽

Independent Prognostic Factor ◽

Short Overall Survival ◽

Leukocyte Counts ◽

Melanoma Patients ◽

Stage Iv Melanoma

Purpose An elevated count of blood neutrophils and monocytes recently was shown independently to predict short survival in patients with stage IV melanoma undergoing interleukin-2–based immunotherapy. In this study, we aimed to validate this finding in a large cohort of stage IV melanoma patients. Patients and Methods For this retrospective prognostic study, the data from the European Organisation for the Research and Treatment of Cancer 18951 study were used. Patients were randomly assigned between treatment with dacarbazine, cisplatin, and interferon alfa with or without interleukin-2. Counts of neutrophils and leukocytes were analyzed together with other known prognostic factors: serum lactate dehydrogenase, performance status, metastatic site, and sex. Two multivariate prognostic factor analyses were carried out in the model: one with leukocyte counts and one with neutrophil counts. Results A total of 363 patients were randomly assigned and baseline blood neutrophil and leukocyte counts were available from 316 and 350 patients, respectively. A high neutrophil count (> 7.5 × 109/L) was an independent prognostic factor for short overall survival (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = 0.02), and a high leukocyte count (> 10 × 109/L) was an independent prognostic factor of both short overall survival (HR, 1.7; 95% CI, 1.3 to 2.4; P = 0.0005) and short progression-free survival (HR, 1.5; 95% CI, 1.1 to 2.1; P = 0.008). Conclusion A high pretreatment count of neutrophils in blood was confirmed as an independent prognostic factor for short overall survival in stage IV melanoma patients undergoing interleukin-2–based immunotherapy. Furthermore, a high count of leukocytes was an independent prognostic factor for short overall survival and progression-free survival. Both parameters should be useful as stratification factors in clinical trials.

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