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Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection

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Abstract

Background

Hepatitis C virus (HCV) interferes with activation of innate and adaptive immune responses. Theoretically, the efficacy and toxicity of immune checkpoint inhibitors in cancer patients infected with HCV may differ. Nevertheless, HCV was an exclusion criterion in most checkpoint inhibitor trials. We evaluated the efficacy and safety of nivolumab in metastatic renal cell carcinoma (mRCC) patients with or without chronic HCV infection.

Methods

In a matched cohort study, data were collected from 174 patients, retrospectively. All patients had clear-cell mRCC, chronic HCV infection (case study group), no evidence of other malignancy or cirrhosis, and had received nivolumab (3 mg/kg every 2 weeks) until disease progression or unacceptable toxicity. Quantitation of HCV RNA in plasma samples was performed before and during treatment with nivolumab with the automated HCV test (Hoffmann-La Roche, Switzerland). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and rate of grade 3–4 adverse events in study and control cohorts.

Results

A total of 44 matched patients were included. Groups were well balanced. HCV-infected patients had significantly longer OS and PFS. Median OS was 27.5 (95% CI 25.3–29.7) and 21.7 (20.3–23.1) in study and control groups, respectively (P = 0.005). Median PFS was 7.5 (5.7–9.3) and 4.9 (4–5.8) (P = 0.013). Despite no differences in ORR between groups (27% vs. 23%, P = 0.7), patients with HCV had significantly more durable responses (P = 0.01). Nivolumab was well tolerated in all HCV-positive patients. No unexpected toxicity was observed. Assessment of viral load during nivolumab therapy was available in 14 of 22 (64%) patients with HCV. Nivolumab did not significantly impact HCV concentration (mean change 210 IU/ml, P = 0.82) in the absence of antiviral therapy.

Conclusions

The efficacy and safety profiles observed in this study support the administration of nivolumab in mRCC patients infected with HCV and warrant further investigation.

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References

  1. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH (2016) Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol 34:539–573

    Article  CAS  Google Scholar 

  2. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264

    Article  CAS  Google Scholar 

  3. Tsimafeyeu I, Zolotareva T, Varlamov S, Zukov R et al (2017) Five-year survival of patients with metastatic renal cell carcinoma in the Russian Federation: results from the RENSUR5 registry. Clin Genitourin Cancer 15(6):e1069–e1072

    Article  Google Scholar 

  4. Wykes MN, Lewin SR (2018) Immune checkpoint blockade in infectious diseases. Nat Rev Immunol 18(2):91–104

    Article  CAS  Google Scholar 

  5. Kaplan DE (2015) Immunopathogenesis of hepatitis C virus infection. Gastroenterol Clin 44:735–760

    Article  Google Scholar 

  6. Wedemeyer H, He XS, Nascimbeni M, Davis AR et al (2002) Impaired effector function of hepatitis C virus-specific CD8 + T cells in chronic hepatitis C virus infection. J Immunol 169(6):3447–3458

    Article  CAS  Google Scholar 

  7. Johnson DB, Sullivan RJ, Menzies AM (2017) Immune checkpoint inhibitors in challenging populations. Cancer 123(11):1904–1911

    Article  Google Scholar 

  8. World Health Organization (2017) Global hepatitis report 2017. World Health Organization, Geneva

    Google Scholar 

  9. Hofmeister MG, Rosenthal EM, Barker LK et al (2019) Estimating prevalence of hepatitis C virus infection in the United States, 2013–2016. Hepatology 69(3):1020–1031

    Article  Google Scholar 

  10. Ramsey SD, Unger JM, Baker LH et al (2019) Prevalence of hepatitis B virus, hepatitis C virus, and HIV infection among patients with newly diagnosed cancer from academic and community oncology practices. JAMA Oncol 5(4):497–505

    Article  Google Scholar 

  11. Tagliamento M, Grossi F, Paolino S et al (2019) Nivolumab treatment in advanced lung cancer patient with chronic active hepatitis C and systemic lupus erythematosus. Immunotherapy 11(10):873–879

    Article  CAS  Google Scholar 

  12. Davar D, Wilson M, Pruckner C et al (2015) PD-1 blockade in advanced melanoma in patients with hepatitis C and/or HIV. Case Rep Oncol Med 2015:737389

    PubMed  PubMed Central  Google Scholar 

  13. Kothapalli A, Khattak MA (2018) Safety and efficacy of anti-PD-1 therapy for metastatic melanoma and non-small-cell lung cancer in patients with viral hepatitis: a case series. Melanoma Res 28(2):155–158

    Article  CAS  Google Scholar 

  14. Khoueiry AB, Sangro B, Yau T et al (2017) Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389(10088):2492–2502

    Article  Google Scholar 

  15. Finn RS, Ryoo B-Y, Merle P et al (2020) Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol 38(3):193–202

    Article  Google Scholar 

  16. Wherry EJ, Kurachi M (2015) Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15(8):486–499

    Article  CAS  Google Scholar 

  17. Salem ML, El-Badawy A (2015) Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy. World J Hepatol 7:2449–2458

    Article  Google Scholar 

  18. Gardiner D, Lalezari J, Lawitz E, DiMicco M, Ghalib R et al (2013) A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection. PLoS One 8:e63818

    Article  Google Scholar 

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Acknowledgements

We are thankful to Anton Barchuk, Ekaterina Kozlova, and Irina Chebykina for excellent research support and technical assistance.

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Authors and Affiliations

  1. Kidney Cancer Research Bureau, Mayakovskogo pereulok 2 off. 1, Moscow, Russia, 109147

    Ilya Tsimafeyeu

  2. Russian Scientific Center of Roentgenoradiology, Moscow, Russia

    Rustem Gafanov

  3. N.N. Petrov Institute of Oncology, St. Petersburg, Russia

    Svetlana Protsenko, Anna Semenova & Ani Oganesyan

  4. Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan

    Nurzhan Nurgaliyev

  5. N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus

    Sergei Krasny

  6. I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Anastasia Bondarenko

  7. Republic Clinical Cancer Center, Kazan, Russia

    Sufia Safina

  8. RakFond, Moscow, Russia

    Kristina Zakurdaeva

Authors
  1. Ilya Tsimafeyeu
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  2. Rustem Gafanov
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  3. Svetlana Protsenko
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  4. Anna Semenova
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  5. Ani Oganesyan
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  6. Nurzhan Nurgaliyev
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  7. Sergei Krasny
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  8. Anastasia Bondarenko
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  9. Sufia Safina
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  10. Kristina Zakurdaeva
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Contributions

Ilya Tsimafeyeu and Kristina Zakurdaeva contributed to conception and design. Ilya Tsimafeyeu, Rustem Gafanov, Svetlana Protsenko, Anna Semenova, Ani Oganesyan, Nurzhan Nurgaliyev, Sergei Krasny, Anastasia Bondarenko, and Sufia Safina were involved in provision of study materials or patients. Ilya Tsimafeyeu, Rustem Gafanov, Svetlana Protsenko, Anna Semenova, Ani Oganesyan, Nurzhan Nurgaliyev, Sergei Krasny, Anastasia Bondarenko, Sufia Safina, and Kristina Zakurdaeva contributed to collection and assembly of data. Ilya Tsimafeyeu, Anastasia Bondarenko, Sufia Safina, and Kristina Zakurdaeva contributed to data analysis and interpretation. Ilya Tsimafeyeu and Kristina Zakurdaeva were involved in manuscript writing. All authors final approved the manuscript. All authors contributed to accountable for all aspects of the work.

Corresponding author

Correspondence to Ilya Tsimafeyeu.

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We declare that the authors have no competing interests, or other interests that might be perceived to influence the results and/or discussion reported in this paper.

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Tsimafeyeu, I., Gafanov, R., Protsenko, S. et al. Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection. Cancer Immunol Immunother 69, 983–988 (2020). https://doi.org/10.1007/s00262-020-02521-y

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  • DOI: https://doi.org/10.1007/s00262-020-02521-y

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