HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma

Adnan Khattak; Oliver Oey; Aesha Gandhi; Anna L Reid; Afaf Abed; Leslie Calapre; Michael Morici; Abha Chopra; Tarek Meniawy; Michael Millward; Melanie Ziman; Elin S. Gray

doi:10.21203/rs.3.rs-1360151/v1

HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma

Adnan Khattak, Oliver Oey, Aesha Gandhi, Anna L Reid, Afaf Abed, Leslie Calapre, Michael Morici, Abha Chopra, Tarek Meniawy, Michael Millward, Melanie Ziman, Elin S. Gray

Research output: Working paper › Preprint

Abstract

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 a worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.

Original language	English
DOIs	https://doi.org/10.21203/rs.3.rs-1360151/v1
Publication status	Published - 28 Feb 2022
Externally published	Yes

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Name	Research Square

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title = "HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma",

abstract = "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 a worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.",

author = "Adnan Khattak and Oliver Oey and Aesha Gandhi and Reid, {Anna L} and Afaf Abed and Leslie Calapre and Michael Morici and Abha Chopra and Tarek Meniawy and Michael Millward and Melanie Ziman and Gray, {Elin S.}",

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T1 - HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma

AU - Khattak, Adnan

AU - Oey, Oliver

AU - Gandhi, Aesha

AU - Reid, Anna L

AU - Abed, Afaf

AU - Calapre, Leslie

AU - Morici, Michael

AU - Chopra, Abha

AU - Meniawy, Tarek

AU - Millward, Michael

AU - Ziman, Melanie

AU - Gray, Elin S.

PY - 2022/2/28

Y1 - 2022/2/28

N2 - 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 a worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.

AB - 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 a worse prognosis compared to non-carriers and may predict reduced response to ICI therapy.

U2 - 10.21203/rs.3.rs-1360151/v1

DO - 10.21203/rs.3.rs-1360151/v1

M3 - Preprint

T3 - Research Square

BT - HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma

ER -

HLA Genotype is Associated With Clinical Outcomes to anti-PD1 Therapy in Advanced Melanoma

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