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Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series

PURPOSE: Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presen...

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Autores principales: Zhou, Chengjing, Jiang, Ting, Xiao, Yajie, Wang, Qiaoxuan, Zeng, Zhifan, Cai, Peiqiang, Zhao, Yongtian, Zhao, Zhikun, Wu, Dongfang, Lin, Hanqing, Sun, Chao, Zhang, Rong, Xiao, Weiwei, Gao, Yuanhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714781/
https://www.ncbi.nlm.nih.gov/pubmed/34975873
http://dx.doi.org/10.3389/fimmu.2021.784336
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author Zhou, Chengjing
Jiang, Ting
Xiao, Yajie
Wang, Qiaoxuan
Zeng, Zhifan
Cai, Peiqiang
Zhao, Yongtian
Zhao, Zhikun
Wu, Dongfang
Lin, Hanqing
Sun, Chao
Zhang, Rong
Xiao, Weiwei
Gao, Yuanhong
author_facet Zhou, Chengjing
Jiang, Ting
Xiao, Yajie
Wang, Qiaoxuan
Zeng, Zhifan
Cai, Peiqiang
Zhao, Yongtian
Zhao, Zhikun
Wu, Dongfang
Lin, Hanqing
Sun, Chao
Zhang, Rong
Xiao, Weiwei
Gao, Yuanhong
author_sort Zhou, Chengjing
collection PubMed
description PURPOSE: Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT). METHODS AND MATERIALS: We assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays. RESULTS: Our analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed. CONCLUSIONS: For advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.
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spelling pubmed-87147812021-12-30 Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series Zhou, Chengjing Jiang, Ting Xiao, Yajie Wang, Qiaoxuan Zeng, Zhifan Cai, Peiqiang Zhao, Yongtian Zhao, Zhikun Wu, Dongfang Lin, Hanqing Sun, Chao Zhang, Rong Xiao, Weiwei Gao, Yuanhong Front Immunol Immunology PURPOSE: Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT). METHODS AND MATERIALS: We assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays. RESULTS: Our analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed. CONCLUSIONS: For advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8714781/ /pubmed/34975873 http://dx.doi.org/10.3389/fimmu.2021.784336 Text en Copyright © 2021 Zhou, Jiang, Xiao, Wang, Zeng, Cai, Zhao, Zhao, Wu, Lin, Sun, Zhang, Xiao and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhou, Chengjing
Jiang, Ting
Xiao, Yajie
Wang, Qiaoxuan
Zeng, Zhifan
Cai, Peiqiang
Zhao, Yongtian
Zhao, Zhikun
Wu, Dongfang
Lin, Hanqing
Sun, Chao
Zhang, Rong
Xiao, Weiwei
Gao, Yuanhong
Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title_full Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title_fullStr Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title_full_unstemmed Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title_short Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
title_sort good tumor response to chemoradioimmunotherapy in dmmr/msi-h advanced colorectal cancer: a case series
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714781/
https://www.ncbi.nlm.nih.gov/pubmed/34975873
http://dx.doi.org/10.3389/fimmu.2021.784336
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