@article{995f09cb66c84da88a003f87f66737f8,
title = "Tumor Junction Burden and Antigen Presentation as Predictors of Survival in Mesothelioma Treated With Immune Checkpoint Inhibitors",
abstract = "Introduction: The favorable outcomes with immunotherapy for mesothelioma were somewhat unexpected because this tumor has a low tumor mutation burden which has been associated with benefit in other cancers. Because chromosomal rearrangements are common in mesothelioma and have neoantigenic potential, we sought to determine whether they are associated with survival in patients treated with immunotherapy. Methods: Pleural biopsies of mesothelioma after at least one line of therapy were obtained from patients (n = 44) before treatment with nivolumab alone (NCT29908324) or in combination with ipilimumab (NCT30660511). RNA and whole-genome sequencing were performed to identify the junctions resulting from chromosomal rearrangements and antigen processing and presentation gene set expression. Associations with overall survival (OS) were estimated using Cox models. An OS cutoff of 1.5 years was used to distinguish patients with and without durable benefit for use in receiving operating characteristic curves. Results: Although tumor junction burdens were not predictive of OS, we identified significant interactions between the junction burdens and multiple antigen processing and presentation gene sets. The “regulation of antigen processing and presentation of peptide antigen” gene set revealed an interaction with tumor junction burden and was predictive of OS. This interaction also predicted 1.5-year or greater survival with an area under the receiving operating characteristic curve of 0.83. This interaction was not predictive of survival in a separate cohort of patients with mesothelioma who did not receive immune checkpoint inhibitors. Conclusions: Analysis of structural variants and antigen presentation gene set expression may facilitate patient selection for immune checkpoint inhibitors.",
keywords = "Chromosomal rearrangements, Immune checkpoint inhibitors, Mesothelioma, Structural variants",
author = "Farhad Kosari and Maria Disselhorst and Jun Yin and Tobias Peikert and Julia Udell and Sarah Johnson and James Smadbeck and Stephen Murphy and Alexa McCune and Giannoula Karagouga and Aakash Desai and Janet Schaefer-Klein and Borad, {Mitesh J.} and John Cheville and George Vasmatzis and Paul Baas and Mansfield, {Aaron S.}",
note = "Funding Information: This work was financially supported by Mark Foundation ASPIRE Award, NCI R21 CA251923, the Barry Family, and Mayo Clinic{\textquoteright}s Center for Individualized Medicine. Funding Information: Disclosure: Dr. Disselhorst reports receiving grants to her institution from and having an advisory role for Bristol-Myers Squibb . Dr. Peikert reports having advisory and consultant work for AstraZeneca with all fees being paid to Mayo Clinic. Dr. Baas reports having advisory and consultancy work for Bristol-Myers Squibb , Merck , Pfizer , Beigene, and Trizell and receiving research grant from Bristol-Myers Squibb and Merck (all payments to the hospital). Dr. Mansfield reports receiving research support from Novartis and Verily; receiving remuneration to his institution for participation on advisory boards for AbbVie , AstraZeneca , Bristol-Myers Squibb , Genentech, and Janssen; receiving travel support and payment from Shanghai Roche Pharmaceuticals Ltd.; and serving as a nonremunerated director of the Mesothelioma Applied Research Foundation. A patent has been filed on the basis of these findings. The remaining authors declare no conflict of interest. Funding Information: Disclosure: Dr. Disselhorst reports receiving grants to her institution from and having an advisory role for Bristol-Myers Squibb. Dr. Peikert reports having advisory and consultant work for AstraZeneca with all fees being paid to Mayo Clinic. Dr. Baas reports having advisory and consultancy work for Bristol-Myers Squibb, Merck, Pfizer, Beigene, and Trizell and receiving research grant from Bristol-Myers Squibb and Merck (all payments to the hospital). Dr. Mansfield reports receiving research support from Novartis and Verily; receiving remuneration to his institution for participation on advisory boards for AbbVie, AstraZeneca, Bristol-Myers Squibb, Genentech, and Janssen; receiving travel support and payment from Shanghai Roche Pharmaceuticals Ltd.; and serving as a nonremunerated director of the Mesothelioma Applied Research Foundation. A patent has been filed on the basis of these findings. The remaining authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2021 International Association for the Study of Lung Cancer",
year = "2021",
doi = "10.1016/j.jtho.2021.10.022",
language = "English (US)",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
}