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. 2021 Feb;6(1):100002.
doi: 10.1016/j.esmoop.2020.100002. Epub 2020 Dec 16.

Molecular profiling of Asian patients with advanced melanoma receiving check-point inhibitor treatment

S Byeon  1 , H J Cho  2 , K-T Jang  3 , M Kwon  4 , J Lee  4 , J Lee  4 , S T Kim  5
Affiliations

Molecular profiling of Asian patients with advanced melanoma receiving check-point inhibitor treatment

S Byeon et al. ESMO Open. 2021 Feb.

Abstract

Objective: Melanoma is major medical challenge and being able to monitor treatment response is critical. This study aimed to use molecular profiling of Asian patients with advanced melanoma who were receiving treatment with check-point inhibitors (CPIs) to identify novel biomarkers of tumor response.

Methods: Next-generation sequencing (NGS) was performed using tumor specimens collected from 178 Asian patients with metastatic melanoma receiving CPIs. The NGS data and clinical-pathological factors were analyzed for potential genetic biomarkers of tumor response to CPI treatment.

Results: The most common melanoma subtype was acral melanoma (40%), followed by cutaneous melanoma (32%), mucosal melanoma (26%), and others (2%). For calculation of treatment efficacy, 164 of the patients could be evaluated. The overall response rate was 45.7%, of which 41 cases exhibited complete responses (25.0%) and 34 showed partial responses (20.7%). There were no significant differences in tumor responses based on melanoma subtype (P = 0.295). Genetically, NRAS mutations, TP53 mutations, and NF2 deletions were significantly associated with resistance to CPIs (P < 0.05). In contrast, MYC and RPS6KB1 amplifications were associated with responsiveness to CPIs (P < 0.05). Median progression-free survival (PFS) for patients treated with CPIs was 5.9 months (95% CI, 3.8-8.05 months). Univariate analysis identified TP53 and BRAF mutations, NF2 deletions, and BIRC2 amplifications as poor prognostic factors for PFS (P < 0.05).

Conclusions: This study determined the integrated genomic profiles of Asian patients with metastatic melanoma receiving CPIs and identified candidate biomarkers that reflected treatment outcomes.

Keywords: check-point inhibitor; melanoma; next-generation sequencing.

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Conflict of interest statement

Acknowledgement A subset of the biospecimens analyzed in this study was provided by Samsung Medical Center Biobank. Disclosure None to declare. Ethics The study was approved by the Institutional Review Board of Samsung Medical Center.

Figures

Figure 1
Figure 1
Somatic gene mutation and copy number alteration profiles of 178 Asian patients with melanoma. Each row represents the genetic alterations and each column represents a single patient. Genetic alterations are indicated in different colors according to type. BR, best response; CR, complete response; NA, not alplicable; N/E, not evaluated; ORR, overall response rate; PFS, progression-free survival; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 2
Figure 2
Ternary diagram of genetic alterations according to melanoma subtype: mucosal, acral, and cutaneous. Genetic alterations with an allele frequency >3% were selected for clear visualization. The size of each circle is relative to the number of patients with that particular genetic alteration. PD-L1, programmed cell death ligand 1; PFS, progression-free survival.
Figure 3
Figure 3
Cox survival analysis for progression-free survival in patients receiving immunotherapy. (A) Univariate analysis, (B) multivariate analysis.
Figure 3
Figure 3
Cox survival analysis for progression-free survival in patients receiving immunotherapy. (A) Univariate analysis, (B) multivariate analysis.
Figure 4
Figure 4
Kaplan–Meier estimates of progression free survival after check point inhibitor (CPI) treatment in melanoma patients. (A) A plot showing survival differences between patients with MSH2 or MLH1 alterations and others. (B) A plot showing survival differences between patients with ≥10 mutations and others. The x-axis represents progression free survival (months) after CPI.
Supplementary Figure S1
Supplementary Figure S1
The total number of mutations and MMR status in 164 melanoma patients. BR, best response.
See this image and copyright information in PMC

References

    1. Guy G.P., Jr., Thomas C.C., Thompson T. Vital signs: melanoma incidence and mortality trends and projections – United States, 1982–2030. MMWR Morb Mortal Wkly Rep. 2015;64(21):591–596. - PMC - PubMed
    1. Gershenwald J.E., Scolyer R.A., Hess K.R. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492. - PMC - PubMed
    1. Barth A., Wanek L.A., Morton D.L. Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg. 1995;181(3):193–201. - PubMed
    1. Curtin J.A., Fridlyand J., Kageshita T. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–2147. - PubMed
    1. Davies H., Bignell G.R., Cox C. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954. - PubMed

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