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; Ryan J Sullivan

doi:10.1038/s41467-024-51722-x

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

Nat Commun. 2024 Aug 27;15(1):7357. doi: 10.1038/s41467-024-51722-x.

Authors

Meghan J Mooradian^#^{1

2}, Florian J Fintelmann^#^{3

4}, Thomas J LaSalle^{5

6

7}, Judit Simon^{3

4}, Alexander Graur⁴, Alona Muzikansky⁸, Mari Mino-Kenudson^{3

9}, Sophia Shalhout¹⁰, Howard L Kaufman^{11

3}, Russell W Jenkins^{11

3}, Donald Lawrence^{11

3}, Aleigha Lawless¹¹, Tatyana Sharova¹², Raul N Uppot^{3

4}, Jacy Fang^{5

6}, Emily M Blaum^{5

6}, Anna L K Gonye^{5

6}, Irena Gushterova^{5

6}, Genevieve M Boland^{3

6

12}, Christopher Azzoli^{11

13}, Nir Hacohen^{5

6}, Moshe Sade-Feldman^{5

6}, Ryan J Sullivan^{11

3}

Affiliations

¹ Division of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA. mmooradian@mgh.harvard.edu.
² Harvard Medical School, Boston, MA, USA. mmooradian@mgh.harvard.edu.
³ Harvard Medical School, Boston, MA, USA.
⁴ Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
⁶ Broad Institute of the Massachusetts Institute of Technology, Boston, MA, USA.
⁷ Program in Health Sciences and Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA.
⁸ Biostatics Department, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Division of Surgical Oncology, Department of Otolaryngology-Head and Neck Surgery, Mass Eye and Ear, Boston, MA, USA.
¹¹ Division of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
¹³ Division of Hematology/Oncology, Lifespan Cancer Institute, Brown University, Providence, RI, USA.

^# Contributed equally.

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.

Publication types

Clinical Trial, Phase II

MeSH terms

Adult
Aged
Aged, 80 and over
Combined Modality Therapy
Cryosurgery* / methods
Disease Progression
Female
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Male
Melanoma* / drug therapy
Melanoma* / immunology
Melanoma* / pathology
Melanoma* / surgery
Middle Aged
Neoplasm Metastasis
Skin Neoplasms / drug therapy
Skin Neoplasms / immunology
Skin Neoplasms / pathology
Skin Neoplasms / surgery
Treatment Outcome
Tumor Microenvironment / immunology

Substances

Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding