HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma Article Swipe
Muhammad Adil Khattak
,
Oliver Oey
,
Aesha Gandhi
,
Anna Reid
,
Afaf Abed
,
Leslie Calapre
,
Michael Morici
,
Abha Chopra
,
Tarek Meniawy
,
Michael Millward
,
Mel Ziman
,
Elin S. Gray
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1360151/v1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1360151/v1
Background:Predictive biomarkers of response to immune checkpoint inhibitors (ICI) are currently being evaluated in many studies. We evaluated whether germline Human Leukocyte Antigen (HLA) status can influence the response to immunotherapy.Materials and Methods:Advanced melanoma patients undergoing treatment with pembrolizumab were recruited between August 2014 to January 2020. 121 patients were recruited, with a median follow up of 40.1 months. We dichotomised the cohort based on homozygosity in one or more HLA-I alleles (n=29) and those with maximal heterozygosity (n=84).Results:Our analysis did not show any association between HLA-I homozygosity and PFS (HR 1.06, 95% CI: 0.60-1.87, p = 0.83) or OS (HR 0.98, 95% CI: 0.51-1.191, p = 0.97). Similarly, we did not find any impact of HLA-II homozygosity (46 homozygous and 67 heterozygous) on PFS (HR 1.08, 95% CI: 0.66-1.79, p = 0.741) or OS (HR 1.52, 95% CI: 0.80-2.85, p = 0.19). Notably, the HLA-B27 supertype was associated with reduced PFS (HR 2.19, 95% CI: 1.19-4.02, p=0.02), and OS (HR:2.20, 95% CI:1.85-4.47, p=0.0075). Multivariate analyses confirmed that the HLA-B27 genotype is an independent predictor of shorter PFS and OS. The HLA-B27 association with reduced OS was validated in an independent cohort of 114 cases from the MSK-IMPACT cohort (HR 3.17, 95% CI: 1.01-10.01, p=0.01).Conclusions:Patients with HLA-B27 supertype have worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-1360151/v1
- https://www.researchsquare.com/article/rs-1360151/latest.pdf
- OA Status
- gold
- References
- 25
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4214708955
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4214708955Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-1360151/v1Digital Object Identifier
- Title
-
HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced MelanomaWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-02-28Full publication date if available
- Authors
-
Muhammad Adil Khattak, Oliver Oey, Aesha Gandhi, Anna Reid, Afaf Abed, Leslie Calapre, Michael Morici, Abha Chopra, Tarek Meniawy, Michael Millward, Mel Ziman, Elin S. GrayList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-1360151/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-1360151/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-1360151/latest.pdfDirect OA link when available
- Concepts
-
Genotype, Human leukocyte antigen, Melanoma, Medicine, Immunology, Oncology, Biology, Cancer research, Genetics, Antigen, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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25Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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