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Plasma exchange and radiation resensitize immunotherapy-refractory melanoma: a phase I trial

Author

Listed:
  • Jacob J. Orme

    (Mayo Clinic
    Mayo Clinic)

  • Henan Zhang

    (Mayo Clinic)

  • Prashanth Lingamaneni

    (Mayo Clinic)

  • Yohan Kim

    (Mayo Clinic)

  • Roxane Lavoie

    (Mayo Clinic)

  • Maddy Dorr

    (Mayo Clinic)

  • Paul Dizona

    (Mayo Clinic)

  • Jacob Hirdler

    (Mayo Clinic)

  • Elizabeth A. Bering

    (Mayo Clinic)

  • Joanina K. Gicobi

    (Mayo Clinic)

  • Michelle Hsu

    (Mayo Clinic)

  • Heather Dale

    (Mayo Clinic)

  • Daniel S. Childs

    (Mayo Clinic)

  • Lisa A. Kottschade

    (Mayo Clinic)

  • Robert R. McWilliams

    (Mayo Clinic)

  • Matthew S. Block

    (Mayo Clinic)

  • Aaron S. Mansfield

    (Mayo Clinic)

  • Svetomir N. Markovic

    (Mayo Clinic)

  • Ken Olivier

    (Mayo Clinic)

  • Dawn Owen

    (Mayo Clinic)

  • Scott Lester

    (Mayo Clinic)

  • Daniel Ma

    (Mayo Clinic)

  • Roxana S. Dronca

    (Mayo Clinic)

  • Haidong Dong

    (Mayo Clinic)

  • Fabrice Lucien

    (Mayo Clinic)

  • Annie T. Packard

    (Mayo Clinic)

  • Jeffrey L. Winters

    (Mayo Clinic)

  • Sean S. Park

    (Mayo Clinic)

Abstract

Immune checkpoint inhibitors (ICI) are effective for advanced melanoma. However, most develop ICI resistance. Tumor-derived soluble PD-L1 (sPD-L1) and other immunosuppressive factors drive resistance. We hypothesized that therapeutic plasma exchange (TPE) may remove sPD-L1 from circulation and overcome ICI resistance. Patients with metastatic ICI-resistant melanoma and elevated sPD-L1 received radiotherapy to a minority of metastatic lesions, TPE, and ICI re-challenge. Primary endpoints were adverse events and sPD-L1 reduction. Secondary endpoints included overall survival, response, and progression-free survival. Correlative studies included changes in sPD-L1, other immunosuppressive factors, and immune cell phenotypes. Eighteen patients were included. Treatment was well-tolerated, and levels of sPD-L1 were reduced by TPE (mean 78%, p

Suggested Citation

  • Jacob J. Orme & Henan Zhang & Prashanth Lingamaneni & Yohan Kim & Roxane Lavoie & Maddy Dorr & Paul Dizona & Jacob Hirdler & Elizabeth A. Bering & Joanina K. Gicobi & Michelle Hsu & Heather Dale & Dan, 2025. "Plasma exchange and radiation resensitize immunotherapy-refractory melanoma: a phase I trial," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57865-9
    DOI: 10.1038/s41467-025-57865-9
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