MP14-02 THE IMPACT OF ZYGOSITY AND SUPERTYPES OF HLA GENOTYPES ON THE CLINICAL OUTCOMES OF PATIENTS WITH GENITOURINARY CANCERS TREATED WITH ANTI-PD-1 DRUGS

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Apr 2020MP14-02 THE IMPACT OF ZYGOSITY AND SUPERTYPES OF HLA GENOTYPES ON THE CLINICAL OUTCOMES OF PATIENTS WITH GENITOURINARY CANCERS TREATED WITH ANTI-PD-1 DRUGS Shintaro Narita*, Nobuhiro Fujiyama, Ryuhei Yamamoto, Atsushi Koizumi, Akane Kikuchi, Ryuichiro Sagehashi, Mizuki Kobayashi, Hiromi Sato, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Takamitsu Inoue, Shigeru Satoh, and Tomonori Habuchi Shintaro Narita*Shintaro Narita* More articles by this author , Nobuhiro FujiyamaNobuhiro Fujiyama More articles by this author , Ryuhei YamamotoRyuhei Yamamoto More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Akane KikuchiAkane Kikuchi More articles by this author , Ryuichiro SagehashiRyuichiro Sagehashi More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Hiromi SatoHiromi Sato More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Sohei KandaSohei Kanda More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000839.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent evidence suggests that patient HLA-I genotypes influence cancer response to checkpoint blockade immunotherapy. In this study, we assessed the impact of zygosity and supertypes of HLA-I and -II genotypes on the clinical outcomes in patients with genitourinary cancers treated with anti-PD-1 drugs. METHODS: We examined the zygosity and HLA supertypes of HLA-I and -II in patients with metastatic renal cell and urothelial carcinomas treated with nivolumab or pembrolizumab using the luminex technique. The HLA-C genotypes were divided into two groups based on the zygosity of their KIR ligands. The impact of homozygosity and each supertype on radiographic response, outcomes, and safety after drug administration was statistically assessed. RESULTS: Of the 51 patients, 21 died and 40 exhibited radiographic progression during the follow-up. Eighteen patients (35.2%) were homozygous for at least one HLA-I loci. Of all patients, the patients with homozygosity for at least one HLA class I loci tended to have better progression-free survival (PFS) than those with heterozygosity for the same (p = 0.088); the HLA supertypes were not associated with clinical outcomes. In renal cell carcinoma, the response rate in patients with homozygosity for at least one HLA-I loci tended to be lower than that in those with heterozygosity for HLA-I loci (p = 0.051). Patients with the HLA-A2 supertype had significantly better PFS than those without the supertype (median PFS: 15 months vs. 3 months, p = 0.037). There was no significant relationship between the presence of adverse events and HLA zygosity/supertypes. In urothelial cancer, HLA class I status was unassociated with clinical outcomes. Furthermore, the HLA-DRB-1 homozygosity and supertypes were unassociated with clinical outcomes in all patients and each cancer type. CONCLUSIONS: Homozygosity and HLA-A2 supertype of the HLA-I loci were prognostic factors in patients with metastatic renal cell carcinoma treated with nivolumab. Germline HLA status has the potential to be associated with clinical outcomes in genitourinary cancer treated with anti-PD-1 drug, although its impact might depend on the cancer type. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e194-e195 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shintaro Narita* More articles by this author Nobuhiro Fujiyama More articles by this author Ryuhei Yamamoto More articles by this author Atsushi Koizumi More articles by this author Akane Kikuchi More articles by this author Ryuichiro Sagehashi More articles by this author Mizuki Kobayashi More articles by this author Hiromi Sato More articles by this author Taketoshi Nara More articles by this author Sohei Kanda More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Shigeru Satoh More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...