Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy
Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.832593/full |
| _version_ | 1818269770678534144 |
|---|---|
| author | Yong Li Yihong Liu Yanchun Qu Xian Chen Xin Qu Yongsong Ye Xiaohua Du Ying Cheng Mian Xu Haibo Zhang |
| author_facet | Yong Li Yihong Liu Yanchun Qu Xian Chen Xin Qu Yongsong Ye Xiaohua Du Ying Cheng Mian Xu Haibo Zhang |
| author_sort | Yong Li |
| collection | DOAJ |
| description | Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study. |
| first_indexed | 2024-12-12T20:59:40Z |
| format | Article |
| id | doaj.art-345dd19c6dc849459ca2abbc01f42e50 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T20:59:40Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-345dd19c6dc849459ca2abbc01f42e502022-12-22T00:12:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.832593832593Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab TherapyYong Li0Yihong Liu1Yanchun Qu2Xian Chen3Xin Qu4Yongsong Ye5Xiaohua Du6Ying Cheng7Mian Xu8Haibo Zhang9Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaDepartment of Medical, Shanghai OrigiMed Co., Ltd, Shanghai, ChinaDepartment of Medical, Shanghai OrigiMed Co., Ltd, Shanghai, ChinaDepartment of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaSoft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient’s disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study.https://www.frontiersin.org/articles/10.3389/fimmu.2022.832593/fullsoft-tissue sarcomastumor mutational burden (TMB)immune checkpoint inhibitorsanlotinibtoripalimab |
| spellingShingle | Yong Li Yihong Liu Yanchun Qu Xian Chen Xin Qu Yongsong Ye Xiaohua Du Ying Cheng Mian Xu Haibo Zhang Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy Frontiers in Immunology soft-tissue sarcomas tumor mutational burden (TMB) immune checkpoint inhibitors anlotinib toripalimab |
| title | Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy |
| title_full | Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy |
| title_fullStr | Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy |
| title_full_unstemmed | Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy |
| title_short | Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy |
| title_sort | case report two cases of soft tissue sarcomas high tmb as a potential predictive biomarker for anlotinib combined with toripalimab therapy |
| topic | soft-tissue sarcomas tumor mutational burden (TMB) immune checkpoint inhibitors anlotinib toripalimab |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.832593/full |
| work_keys_str_mv | AT yongli casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT yihongliu casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT yanchunqu casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT xianchen casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT xinqu casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT yongsongye casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT xiaohuadu casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT yingcheng casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT mianxu casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy AT haibozhang casereporttwocasesofsofttissuesarcomashightmbasapotentialpredictivebiomarkerforanlotinibcombinedwithtoripalimabtherapy |