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Preexisting Autoantibodies and Immune Related Adverse Events in Metastatic Urothelial Carcinoma Patients Treated by Pembrolizumab

  • Zahra Castel-Ajgal
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Claire Goulvestre
    Affiliations
    Department of Urology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Université de Paris, Paris, France
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  • Sonia Zaibet
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Jennifer Arrondeau
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Marie Bretagne
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Michael Peyromaure
    Affiliations
    Department of Immunology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Université de Paris, Paris, France
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  • Fréderic Batteux
    Affiliations
    Department of Urology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Université de Paris, Paris, France
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  • Jerome Alexandre
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Francois Goldwasser
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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  • Olivier Huillard
    Correspondence
    Address for correspondence: Olivier Huillard, MD, PhD, Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, 123 boulevard de Port Royal, 75014 Paris, France
    Affiliations
    Department of Medical Oncology, Hôpital Cochin Port Royal, AP-HP, Paris, France; Cancer Research for Personalized Medicine (CARPEM), Paris, France; Université de Paris, Paris, France
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Published:April 21, 2022DOI:https://doi.org/10.1016/j.clgc.2022.04.002

      Highlights

      • No predictive biomarker of immune related adverse events exists.
      • We assessed the predictive value of ANA for toxicity of pembrolizumab.
      • Presence of ANA >160 was significantly associated with iRAE and limiting toxicity.
      • iRAE tend to occur before the third cycle for patients with ANA >1/160.
      • We found no association between efficacy parameters and ANA >1/160.

      Abstract

      Introduction

      Immune checkpoint inhibitor are standard therapy in metastatic urothelial carcinoma. No predictive biomarker of immune related adverse events (iRAE) exists. Antinuclear antibodies (ANA) can be the sign of a subclinical autoimmune condition that could be enhanced by Immune checkpoint inhibitor. We decided to assess the predictive value of baseline autoantibodies and ANA for iRAE in metastatic urothelial carcinoma patients treated with pembrolizumab and explore their prognostic signification.

      Patients and Method

      Data concerning patients treated in our institution between 2015 and 2020 with pembrolizumab for metastatic urothelial carcinoma with available baseline value of ANA and other autoantibodies was collected. ANA with titer >1/80 were defined positive.

      Results

      A total of 68 patients were included. Fifty-five (80%) had ANA >1/80 and among them 21 patients (30%) had ANA >1/160. Seven patients with ANA >160 (33%) presented iRAE vs. 5 patients (10%) in the rest of the population. Presence of ANA >160 was significantly associated with iRAE (P = .029) and limiting toxicity (P = .048) in univariate analysis. iRAE tend to occur earlier, before the third cycle, for patients with ANA >1/160 as compared to rest of the patients (28% vs. 6%, P = .052). Exploratory analysis did not reveal correlation between progression free survival or overall survival and ANA >1/160 in univariate or in multivariate analysis including the Bellmunt score (HR = 0.7, 95%CI [0.38-1.35], P = .5).

      Conclusion

      The presence of ANA >1/160 is associated with iRAE and limiting toxicity of pembrolizumab.

      Keywords

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