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Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma
Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinom...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569213/ https://www.ncbi.nlm.nih.gov/pubmed/34737281 http://dx.doi.org/10.1038/s41467-021-26415-4 |
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author | Campbell, Matthew T. Matin, Surena F. Tam, Alda L. Sheth, Rahul A. Ahrar, Kamran Tidwell, Rebecca S. Rao, Priya Karam, Jose A. Wood, Christopher G. Tannir, Nizar M. Jonasch, Eric Gao, Jianjun Zurita, Amado J. Shah, Amishi Y. Jindal, Sonali Duan, Fei Basu, Sreyashi Chen, Hong Espejo, Alexsandra B. Allison, James P. Yadav, Shalini S. Sharma, Padmanee |
author_facet | Campbell, Matthew T. Matin, Surena F. Tam, Alda L. Sheth, Rahul A. Ahrar, Kamran Tidwell, Rebecca S. Rao, Priya Karam, Jose A. Wood, Christopher G. Tannir, Nizar M. Jonasch, Eric Gao, Jianjun Zurita, Amado J. Shah, Amishi Y. Jindal, Sonali Duan, Fei Basu, Sreyashi Chen, Hong Espejo, Alexsandra B. Allison, James P. Yadav, Shalini S. Sharma, Padmanee |
author_sort | Campbell, Matthew T. |
collection | PubMed |
description | Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology. |
format | Online Article Text |
id | pubmed-8569213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85692132021-11-15 Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma Campbell, Matthew T. Matin, Surena F. Tam, Alda L. Sheth, Rahul A. Ahrar, Kamran Tidwell, Rebecca S. Rao, Priya Karam, Jose A. Wood, Christopher G. Tannir, Nizar M. Jonasch, Eric Gao, Jianjun Zurita, Amado J. Shah, Amishi Y. Jindal, Sonali Duan, Fei Basu, Sreyashi Chen, Hong Espejo, Alexsandra B. Allison, James P. Yadav, Shalini S. Sharma, Padmanee Nat Commun Article Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology. Nature Publishing Group UK 2021-11-04 /pmc/articles/PMC8569213/ /pubmed/34737281 http://dx.doi.org/10.1038/s41467-021-26415-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Campbell, Matthew T. Matin, Surena F. Tam, Alda L. Sheth, Rahul A. Ahrar, Kamran Tidwell, Rebecca S. Rao, Priya Karam, Jose A. Wood, Christopher G. Tannir, Nizar M. Jonasch, Eric Gao, Jianjun Zurita, Amado J. Shah, Amishi Y. Jindal, Sonali Duan, Fei Basu, Sreyashi Chen, Hong Espejo, Alexsandra B. Allison, James P. Yadav, Shalini S. Sharma, Padmanee Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title | Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title_full | Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title_fullStr | Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title_full_unstemmed | Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title_short | Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
title_sort | pilot study of tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569213/ https://www.ncbi.nlm.nih.gov/pubmed/34737281 http://dx.doi.org/10.1038/s41467-021-26415-4 |
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