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Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial

Author

Listed:
  • Meghan J. Mooradian

    (Massachusetts General Hospital
    Harvard Medical School)

  • Florian J. Fintelmann

    (Harvard Medical School
    Massachusetts General Hospital)

  • Thomas J. LaSalle

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology
    Harvard Medical School & Massachusetts Institute of Technology)

  • Judit Simon

    (Harvard Medical School
    Massachusetts General Hospital)

  • Alexander Graur

    (Massachusetts General Hospital)

  • Alona Muzikansky

    (Massachusetts General Hospital)

  • Mari Mino-Kenudson

    (Harvard Medical School
    Massachusetts General Hospital)

  • Sophia Shalhout

    (Mass Eye and Ear)

  • Howard L. Kaufman

    (Massachusetts General Hospital
    Harvard Medical School)

  • Russell W. Jenkins

    (Massachusetts General Hospital
    Harvard Medical School)

  • Donald Lawrence

    (Massachusetts General Hospital
    Harvard Medical School)

  • Aleigha Lawless

    (Massachusetts General Hospital)

  • Tatyana Sharova

    (Massachusetts General Hospital)

  • Raul N. Uppot

    (Harvard Medical School
    Massachusetts General Hospital)

  • Jacy Fang

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Emily M. Blaum

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Anna L. K. Gonye

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Irena Gushterova

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Genevieve M. Boland

    (Harvard Medical School
    Broad Institute of the Massachusetts Institute of Technology
    Massachusetts General Hospital)

  • Christopher Azzoli

    (Massachusetts General Hospital
    Brown University)

  • Nir Hacohen

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Moshe Sade-Feldman

    (Massachusetts General Hospital Cancer Center
    Broad Institute of the Massachusetts Institute of Technology)

  • Ryan J. Sullivan

    (Massachusetts General Hospital
    Harvard Medical School)

Abstract

Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that cryoablation may modify the immune microenvironment through direct modulation of the tumor, thereby generating an anti-tumor response in tumors refractory to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent cryoablation of an enlarging metastasis, and ICI was continued for a minimum of two additional cycles. The primary endpoints were safety, feasibility and tumor response in non-ablated lesions. From May 2018 through July 2020, 17 patients were treated on study. The study met its primary endpoints with the combination strategy found to be safe and feasible with an objective response rate of 23.5% and disease control rate of 41% (4 partial response, 3 stable disease). Our data support further study of this synergistic therapeutic approach.

Suggested Citation

  • Meghan J. Mooradian & Florian J. Fintelmann & Thomas J. LaSalle & Judit Simon & Alexander Graur & Alona Muzikansky & Mari Mino-Kenudson & Sophia Shalhout & Howard L. Kaufman & Russell W. Jenkins & Don, 2024. "Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51722-x
    DOI: 10.1038/s41467-024-51722-x
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    References listed on IDEAS

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    1. Hussein Al-Mossawi & Nicole Yager & Chelsea A. Taylor & Evelyn Lau & Sara Danielli & Jelle Wit & James Gilchrist & Isar Nassiri & Elise A. Mahe & Wanseon Lee & Laila Rizvi & Seiko Makino & Jane Cheese, 2019. "Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Shohei Koyama & Esra A. Akbay & Yvonne Y. Li & Grit S. Herter-Sprie & Kevin A. Buczkowski & William G. Richards & Leena Gandhi & Amanda J. Redig & Scott J. Rodig & Hajime Asahina & Robert E. Jones & M, 2016. "Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    3. Julie M. Mazet & Jagdish N. Mahale & Orion Tong & Robert A. Watson & Ana Victoria Lechuga‐Vieco & Gabriela Pirgova & Vivian W. C. Lau & Moustafa Attar & Lada A. Koneva & Stephen N. Sansom & Benjamin P, 2023. "IFNγ signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
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