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Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators

Authors
 Hwa Kyung Byun  ;  Jee Suk Chang  ;  Minkyu Jung  ;  Woong Sub Koom  ;  Kee Yang Chung  ;  Byung Ho Oh  ;  Mi Ryung Roh  ;  Kyung Hwan Kim  ;  Choong-Kun Lee  ;  Sang Joon Shin 
Citation
 FRONTIERS IN ONCOLOGY, Vol.11(1) : 659754, 2021-05 
Journal Title
FRONTIERS IN ONCOLOGY
Issue Date
2021-05
Keywords
immune checkpoint blockade ; lymphopenia ; melanoma ; overall survival ; predictor
Abstract
Background: Immune checkpoint blocker (ICB) has shown significant clinical activity in melanoma. However, there are no clinically approved biomarkers to aid patient selection. We aimed to identify patients with advanced or metastatic melanoma who are likely to benefit from ICB monotherapy using easily accessible clinical indicators.

Materials and methods: We retrospectively reviewed the records of 134 patients with advanced or metastatic melanoma who received ICB monotherapy between 2014 and 2018. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were determined using Cox regression analysis.

Results: During the median follow-up of 13.7 months, the median OS and PFS were 18.4 and 3.4 months, respectively. Visceral/central nervous system (CNS) metastasis (OS: adjusted hazards ratio [HR], 1.82; p=.014; PFS: HR, 1.59; p=.024), lymphopenia (<1000 cells/µL) within 3 months (OS: HR, 1.89, p=.006; PFS: HR, 1.70; p=.010), and elevated baseline lactate dehydrogenase (LDH) level (OS: HR, 2.61; p<.001; PFS: HR, 2.66; p<.001) were independent prognostic factors for both poor OS and PFS. Development of immune-related adverse events (irAE; e.g., hypothyroidism or vitiligo) within 6 months showed a trend toward better OS in multivariable analysis (HR, 0.37; p=.058). Patients with normal LDH levels and no visceral/CNS metastasis had a substantially better OS than the others (median, 40.4 vs. 13.6 months; p<.001). Among others, patients who developed irAE within 6 months achieved long-term OS (median, 43.6 vs. 13.1 months; p=.008). A decision tree was suggested using four risk factors, and the risk stratification provided significant distinction between the survival curves.

Conclusion: The four easily accessible clinical indicators associated with better treatment outcomes after ICB monotherapy in patients with advanced or metastatic melanoma were LDH level, the extent of disease, lymphopenia, and irAE. The combined use of these indicators can be clinically useful in improving risk stratification of patients treated with ICB monotherapy.
Files in This Item:
T202102886.pdf Download
DOI
10.3389/fonc.2021.659754
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Koom, Woong Sub(금웅섭) ORCID logo https://orcid.org/0000-0002-9435-7750
Kim, Kyung Hwan(김경환)
Roh, Mi Ryung(노미령) ORCID logo https://orcid.org/0000-0002-6285-2490
Byun, Hwa Kyung(변화경) ORCID logo https://orcid.org/0000-0002-8964-6275
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Oh, Byung Ho(오병호) ORCID logo https://orcid.org/0000-0001-9575-5665
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
Chung, Kee Yang(정기양) ORCID logo https://orcid.org/0000-0003-3257-0297
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184337
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