Dataset Information

Long-term outcomes of helper peptide vaccination for metastatic melanoma.

ABSTRACT:

Objective

The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls.

Background

A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses.

Methods

The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4+ T cell responses were measured by proliferation or direct IFN-gamma ELIspot assay. Overall survival of vaccinated patients was compared to a group of clinically comparable historical controls using multivariable Cox regression analysis and Kaplan-Meier survival analysis, taking into account age, metastatic site, and resection status.

Results

Across 40 vaccinated patients and 87 controls, resection status (HR 0.54, P = 0.004) and vaccination (HR 0.24, P < 0.001) were associated with improved overall survival. Forty pairs of vaccinated patients and controls were matched by metastatic site, resection status, and age within 10 years. Median survival was significantly longer for vaccinated patients (5.4 vs 1.3 years, P < 0.001). Among the vaccinated patients, the development of a specific immune response after vaccination was associated with improved survival (HR 0.35, P = 0.040).

Conclusions

Helper peptide vaccination is associated with improved overall survival among patients with metastatic melanoma. These data support a randomized prospective trial of the 6MHP vaccine.

SUBMITTER: Hu Y

PROVIDER: S-EPMC4756583 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term outcomes of helper peptide vaccination for metastatic melanoma.

Hu Yinin Y Kim Helen H Blackwell Christopher M CM Slingluff Craig L CL

Annals of surgery 20150901 3

<h4>Objective</h4>The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls.<h4>Background</h4>A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses.<h4>Methods</h4>The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4 ...[more]

PMID: 26258314

Similar Datasets

Project description:Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

Project description:BackgroundWe have previously published initial efficacy of the indoleamine 2,3-dioxygenase (IDO)/anti-programmed death ligand 1 (PD-L1) vaccine in combination with nivolumab in 30 anti-PD-1 therapy naïve patients with metastatic melanoma (cohort A). We now report long-term follow-up of patients in cohort A. Further, we report results from cohort B, where the peptide vaccine was added to anti-PD-1 therapy for patients with progressive disease during anti-PD-1 treatment.MethodsAll patients were treated with a therapeutic peptide vaccine in Montanide targeting IDO and PD-L1 combined with nivolumab (NCT03047928). A long-term follow-up of safety, response rates, and survival rates were performed in cohort A including patient subgroup analyses. Safety and clinical responses were analyzed for cohort B.ResultsCohort A: At data cut-off, January 5, 2023, the overall response rate (ORR) was 80%, and 50% of the 30 patients obtained a complete response (CR). The median progression-free survival (mPFS) was 25.5 months (95% CI 8.8 to 39), and median overall survival (mOS) was not reached (NR) (95% CI 36.4 to NR). The minimum follow-up time was 29.8 months, and the median follow-up was 45.3 months (IQR 34.8-59.2). A subgroup evaluation further revealed that cohort A patients with unfavorable baseline characteristics, including either PD-L1 negative tumors (n=13), elevated lactate dehydrogenase (LDH) levels (n=11), or M1c (n=17) obtained both favorable response rates and durable responses. The ORR was 61.5%, 79%, and 88% for patients with PD-L1- tumors, elevated LDH, and M1c, respectively. The mPFS was 7.1 months for patients with PD-L1- tumors, 30.9 months for patients with elevated LDH, and 27.9 months for M1c patients. Cohort B: At data cut-off, the best overall response was stable disease for 2 of the 10 evaluable patients. The mPFS was 2.4 months (95% CI 1.38 to 2.52), and the mOS was 16.7 months (95% CI 4.13 to NR).ConclusionThis long-term follow-up confirms the promising and durable responses in cohort A. Subgroup analyses of patients with unfavorable baseline characteristics revealed that high response rates and survival rates were also found in patients with either PD-L1 negative tumors, elevated LDH levels, or M1c. No meaningful clinical effect was demonstrated in cohort B patients.Trial registration numberNCT03047928.

Dataset Information

Long-term outcomes of helper peptide vaccination for metastatic melanoma.

Objective

Background

Methods

Results

Conclusions

Publications

Long-term outcomes of helper peptide vaccination for metastatic melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets