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

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, Donald Lawrence, Aleigha Lawless, Tatyana Sharova, Raul N. Uppot, Jacy Fang, Emily M. Blaum, Anna L. K. Gonye, Irena Gushterova, Genevieve M. Boland, Christopher Azzoli, Nir Hacohen, Moshe Sade-Feldman and Ryan J. Sullivan
Additional contact information
Meghan J. Mooradian: Massachusetts General Hospital
Florian J. Fintelmann: Harvard Medical School
Thomas J. LaSalle: Massachusetts General Hospital Cancer Center
Judit Simon: Harvard Medical School
Alexander Graur: Massachusetts General Hospital
Alona Muzikansky: Massachusetts General Hospital
Mari Mino-Kenudson: Harvard Medical School
Sophia Shalhout: Mass Eye and Ear
Howard L. Kaufman: Massachusetts General Hospital
Russell W. Jenkins: Massachusetts General Hospital
Donald Lawrence: Massachusetts General Hospital
Aleigha Lawless: Massachusetts General Hospital
Tatyana Sharova: Massachusetts General Hospital
Raul N. Uppot: Harvard Medical School
Jacy Fang: Massachusetts General Hospital Cancer Center
Emily M. Blaum: Massachusetts General Hospital Cancer Center
Anna L. K. Gonye: Massachusetts General Hospital Cancer Center
Irena Gushterova: Massachusetts General Hospital Cancer Center
Genevieve M. Boland: Harvard Medical School
Christopher Azzoli: Massachusetts General Hospital
Nir Hacohen: Massachusetts General Hospital Cancer Center
Moshe Sade-Feldman: Massachusetts General Hospital Cancer Center
Ryan J. Sullivan: Massachusetts General Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51722-x

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