Response to Checkpoint Inhibitor Therapy in Advanced Classic Kaposi Sarcoma: A Case Report and Immunogenomic Study

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Kaposi sarcoma (KS) is an uncommon angioproliferative malignancy that is associated with human herpesvirus 8. Although there has been recent enthusiasm for evaluating immune checkpoint inhibition as a therapeutic option for viral-associated tumors, the clinical utility in this disease is currently unknown. We report a case of advanced classic KS refractory to multiple lines of chemotherapy that experienced a partial response to anti–PD-1 therapy. Comprehensive molecular profiling was performed on a diagnostic tumor biopsy sample. Molecular profiling data from 8 additional male patients with KS were reviewed and compared with those of the index case. The genomic profile of the index case was notable for higher-than-typical somatic mutational burden, including pathogenic mutation in multiple well-described cancer genes, such as TP53, CDKN2A, NOTCH1, and KRAS. Our case suggests that further clinical study of checkpoint inhibitor therapy in classic KS is warranted, and provides a hypothesis for future immunogenomic biomarker analysis in this disease.

Correspondence: Andrew S. Brohl, MD, Sarcoma Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. Email: andrew.brohl@moffitt.org
  • 1.

    Stiller CA, Trama A, Brewster DH. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project. Cancer Epidemiol 2014;38:670678.

    • Search Google Scholar
    • Export Citation
  • 2.

    Regnier-Rosencher E, Guillot B, Dupin N. Treatments for classic Kaposi sarcoma: a systematic review of the literature. J Am Acad Dermatol 2013;68:313331.

    • Search Google Scholar
    • Export Citation
  • 3.

    Di Lorenzo G, Kreuter A, Di Trolio R. Activity and safety of pegylated liposomal doxorubicin as first-line therapy in the treatment of non-visceral classic Kaposi's sarcoma: a multicenter study. J Invest Dermatol 2008;128:15781580.

    • Search Google Scholar
    • Export Citation
  • 4.

    Paydas S, Bagir EK, Deveci MA, Gonlusen G. Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas. Med Oncol 2016;33:93.

  • 5.

    Beldi-Ferchiou A, Lambert M, Dogniaux S. PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma. Oncotarget 2016;7:7296172977.

    • Search Google Scholar
    • Export Citation
  • 6.

    Goodman AM, Kato S, Bazhenova L. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 2017;16:25982608.

    • Search Google Scholar
    • Export Citation
  • 7.

    Johnson DB, Frampton GM, Rioth MJ. Targeted next generation sequencing identifies markers of response to PD-1 blockade. Cancer Immunol Res 2016;4:959967.

    • Search Google Scholar
    • Export Citation
  • 8.

    Frampton GM, Fichtenholtz A, Otto GA. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013;31:10231031.

    • Search Google Scholar
    • Export Citation
  • 9.

    Liu Z, Fang Q, Zuo J. Global epidemiology of human herpesvirus 8 in men who have sex with men: a systematic review and meta-analysis. J Med Virol 2018;90:582591.

    • Search Google Scholar
    • Export Citation
  • 10.

    Royse KE, El Chaer F, Amirian ES. Disparities in Kaposi sarcoma incidence and survival in the United States: 2000-2013. PLoS One 2017;12:e0182750.

    • Search Google Scholar
    • Export Citation
  • 11.

    Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 2016;17:e542551a.

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