Header

UZH-Logo

Maintenance Infos

Melanoma Immunotherapy: Next-Generation Biomarkers


Hogan, Sabrina A; Levesque, Mitchell P; Cheng, Phil F (2018). Melanoma Immunotherapy: Next-Generation Biomarkers. Frontiers in Oncology:8:178.

Abstract

The recent emergence of cancer immunotherapies initiated a significant shift in the clinical management of metastatic melanoma. Prior to 2011, melanoma patients only had palliative treatment solutions which offered little to no survival benefit. In 2018, with immunotherapy, melanoma patients can now contemplate durable or even complete remission. Treatment with novel immune checkpoint inhibitors, anti-cytotoxic T-lymphocyte protein 4 and anti-programmed cell death protein 1, clearly result in superior median and long-term survivals compared to standard chemotherapy; however, more than half of the patients do not respond to immune checkpoint blockade. Currently, clinicians do not have any effective way to stratify melanoma patients for immunotherapies. Research is now focusing on identifying biomarkers which could predict a patient’s response prior treatment initiation (or very early during treatment course), in order to maximize therapeutic efficacy, avoid unnecessary costs, and undesirable heavy side effects for the patient. Given the rapid developments in this field and the translational potential for some of the biomarkers, we will summarize the current state of biomarker research for immunotherapy in melanoma, with an emphasis on omics technologies such as next-generation sequencing and mass cytometry (CyTOF).
Immunotherapy has revolutionized the management of metastatic melanoma. Prior to 2011, the median survival for metastatic melanoma was 9 months, compared to greater than 18 months in 2017 (1). Patients now benefit from novel immune checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1). From the latest survival data of the Checkmate 067 trial, progression-free survival (PFS) for ipilimumab is 2.9 months, for nivolumab 6.9 months, and for the combination of nivolumab and ipilimumab 11.5 months. Overall survival (OS) of the ipilimumab group was 19.9 and 37.6 months for the nivolumab group. Median OS was not reached in the combination nivolumab and ipilimumab group with a minimum follow-up time of 36 months (2–6). Although OS is extended, not all patients benefit from immunotherapy. Response rates for ipilimumab range from 11% to 19% (4, 5) and for pembrolizumab or nivolumab from 33% to 44% (2, 6, 7). These new ICIs clearly show superior median and long-term survivals compared to standard chemotherapy; however, more than half of the patients do not respond to immune checkpoint blockade. Currently, there are no clinically approved biomarkers to aid in patient selection in melanoma. In this review, we seek to delineate the current state of biomarker research for immunotherapy in melanoma, with an emphasis on omics technologies such as next-generation sequencing (NGS) and mass cytometry (CyTOF). Given the urgent clinical need for such biomarkers, we decided to focus on human studies only, which we think are more clinically relevant.

Abstract

The recent emergence of cancer immunotherapies initiated a significant shift in the clinical management of metastatic melanoma. Prior to 2011, melanoma patients only had palliative treatment solutions which offered little to no survival benefit. In 2018, with immunotherapy, melanoma patients can now contemplate durable or even complete remission. Treatment with novel immune checkpoint inhibitors, anti-cytotoxic T-lymphocyte protein 4 and anti-programmed cell death protein 1, clearly result in superior median and long-term survivals compared to standard chemotherapy; however, more than half of the patients do not respond to immune checkpoint blockade. Currently, clinicians do not have any effective way to stratify melanoma patients for immunotherapies. Research is now focusing on identifying biomarkers which could predict a patient’s response prior treatment initiation (or very early during treatment course), in order to maximize therapeutic efficacy, avoid unnecessary costs, and undesirable heavy side effects for the patient. Given the rapid developments in this field and the translational potential for some of the biomarkers, we will summarize the current state of biomarker research for immunotherapy in melanoma, with an emphasis on omics technologies such as next-generation sequencing and mass cytometry (CyTOF).
Immunotherapy has revolutionized the management of metastatic melanoma. Prior to 2011, the median survival for metastatic melanoma was 9 months, compared to greater than 18 months in 2017 (1). Patients now benefit from novel immune checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1). From the latest survival data of the Checkmate 067 trial, progression-free survival (PFS) for ipilimumab is 2.9 months, for nivolumab 6.9 months, and for the combination of nivolumab and ipilimumab 11.5 months. Overall survival (OS) of the ipilimumab group was 19.9 and 37.6 months for the nivolumab group. Median OS was not reached in the combination nivolumab and ipilimumab group with a minimum follow-up time of 36 months (2–6). Although OS is extended, not all patients benefit from immunotherapy. Response rates for ipilimumab range from 11% to 19% (4, 5) and for pembrolizumab or nivolumab from 33% to 44% (2, 6, 7). These new ICIs clearly show superior median and long-term survivals compared to standard chemotherapy; however, more than half of the patients do not respond to immune checkpoint blockade. Currently, there are no clinically approved biomarkers to aid in patient selection in melanoma. In this review, we seek to delineate the current state of biomarker research for immunotherapy in melanoma, with an emphasis on omics technologies such as next-generation sequencing (NGS) and mass cytometry (CyTOF). Given the urgent clinical need for such biomarkers, we decided to focus on human studies only, which we think are more clinically relevant.

Statistics

Citations

Dimensions.ai Metrics
3 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

13 downloads since deposited on 06 Jun 2018
13 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2018
Deposited On:06 Jun 2018 13:15
Last Modified:17 Feb 2019 06:50
Publisher:Frontiers Research Foundation
ISSN:2234-943X
Additional Information:European Union (EU), Horizon 2020
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fonc.2018.00178
Project Information:
  • : FunderH2020
  • : Grant ID641458
  • : Project TitleMELanoma GENetics - understanding and biomarking the genetic and immunological determinants of melanoma survival

Download

Download PDF  'Melanoma Immunotherapy: Next-Generation Biomarkers'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)