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Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma

Overview of attention for article published in Journal for Immunotherapy of Cancer, November 2017
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  • Good Attention Score compared to outputs of the same age (68th percentile)

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8 X users

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40 Dimensions

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78 Mendeley
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Title
Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma
Published in
Journal for Immunotherapy of Cancer, November 2017
DOI 10.1186/s40425-017-0290-x
Pubmed ID
Authors

Rahima Jamal, Réjean Lapointe, Eftihia Cocolakis, Paméla Thébault, Shirin Kazemi, Jennifer E. Friedmann, Jeanne Dionne, Jean-François Cailhier, Karl Bélanger, Jean-Pierre Ayoub, Huy Le, Caroline Lambert, Jida El-Hajjar, Léon C. van Kempen, Alan Spatz, Wilson H. Miller

Abstract

Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers. Thirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP. Adverse events (AEs) were monitored and response to treatment was evaluated. Tumor tissue and peripheral blood were collected at specified time points to characterize tumor immune markers by immunohistochemistry and systemic immune activity by multiplex assays and flow cytometry. Eighty three percent of patients received all 5 cycles of CP and 93% completed ipilimumab induction. Serious AEs occurred in 13% of patients, and no treatment-related deaths were observed. Best Overall Response Rate (BORR) and Disease Control Rate (DCR) were 27 and 57%, respectively. Median overall survival was 16.2 months. Response to treatment was positively correlated with a higher tumor CD3(+) infiltrate (immune score) at baseline. NRAS and BRAF mutations were less frequent in patients who experienced clinical benefit. Assessment of peripheral blood revealed that non-responders had elevated baseline levels of CXCL8 and CCL4, and a higher proportion of circulating late differentiated B cells. Pre-existing high levels of chemokines (CCL3, CCL4 and CXCL8) and advanced B cell differentiation were strongly associated with worse patient overall survival. Elevated proportions of circulating CD8(+)/PD-1(+) T cells during treatment were associated with worse survival. The combination of ipilimumab and CP was well tolerated and revealed novel characteristics associated with patients likely to benefit from treatment. A pre-existing systemic inflammatory state characterized by elevation of selected chemokines and advanced B cell differentiation, was strongly associated with poor patient outcomes, revealing potential predictive circulating biomarkers. Clinicaltrials.gov , NCT01676649 , registered on August 29, 2012.

X Demographics

X Demographics

The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 78 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 13%
Student > Bachelor 9 12%
Student > Ph. D. Student 8 10%
Other 7 9%
Student > Master 6 8%
Other 12 15%
Unknown 26 33%
Readers by discipline Count As %
Medicine and Dentistry 20 26%
Biochemistry, Genetics and Molecular Biology 10 13%
Agricultural and Biological Sciences 4 5%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Immunology and Microbiology 3 4%
Other 6 8%
Unknown 31 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 June 2018.
All research outputs
#7,716,445
of 25,382,440 outputs
Outputs from Journal for Immunotherapy of Cancer
#1,838
of 3,422 outputs
Outputs of similar age
#139,559
of 445,582 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#25
of 27 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 3,422 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 445,582 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.