Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization
Sarcomas are traditionally considered “cold” tumors with poor response to immunotherapy. However, evidence accumulating over the last years shows that immune checkpoint inhibitors (ICIs) may have a role in selected sarcoma patients according to predictive markers. Here, we report the case of a woman...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1485386/full |
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| author | Daniela A. Ferraro Bettina Bisig Bettina Bisig David C. Rotzinger Fresia Pareja Edoardo Missiaglia Edoardo Missiaglia Ioannis Voutsadakis Ioannis Voutsadakis Krisztian Homicsko Krisztian Homicsko Antonia Digklia Antonia Digklia |
| author_facet | Daniela A. Ferraro Bettina Bisig Bettina Bisig David C. Rotzinger Fresia Pareja Edoardo Missiaglia Edoardo Missiaglia Ioannis Voutsadakis Ioannis Voutsadakis Krisztian Homicsko Krisztian Homicsko Antonia Digklia Antonia Digklia |
| author_sort | Daniela A. Ferraro |
| collection | DOAJ |
| description | Sarcomas are traditionally considered “cold” tumors with poor response to immunotherapy. However, evidence accumulating over the last years shows that immune checkpoint inhibitors (ICIs) may have a role in selected sarcoma patients according to predictive markers. Here, we report the case of a woman diagnosed with a primary cardiac undifferentiated sarcoma. Following failure of standard first line chemotherapy, high-throughput sequencing (HTS) revealed a high tumor mutational burden (TMB), pathogenic mutations in FAT1 and NOTCH2 and a microsatellite instability (MSI)-associated signature. Immunohistochemistry confirmed mismatch repair-deficiency (MMRd) and abundant CD8+ tumor-infiltrating lymphocytes (TILs), in the absence of tertiary lymphoid structures. The patient was, therefore, treated with the ICI pembrolizumab, reaching a complete response that continues to persist at last follow-up, more than seven years from initial diagnosis and nearly six years from initiation of ICI treatment. This case illustrates the importance of performing HTS in rare sarcomas given the availability of efficient therapies, such as those for tumors displaying high TMB or MMRd/MSI. In agreement with other reports, it supports the contention that MMRd/MSI status and high numbers of TILs are valuable predictive markers of response to immunotherapy in sarcomas. |
| format | Article |
| id | doaj-art-58d020f23c6d4e80aad3cc8ccc58b921 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-58d020f23c6d4e80aad3cc8ccc58b9212025-08-20T03:03:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.14853861485386Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterizationDaniela A. Ferraro0Bettina Bisig1Bettina Bisig2David C. Rotzinger3Fresia Pareja4Edoardo Missiaglia5Edoardo Missiaglia6Ioannis Voutsadakis7Ioannis Voutsadakis8Krisztian Homicsko9Krisztian Homicsko10Antonia Digklia11Antonia Digklia12Department of Medical Oncology, CHUV University Hospital, Lausanne, SwitzerlandInstitute of Pathology, Department of Laboratory Medicine and Pathology, CHUV University Hospital, Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Radiology, CHUV University Hospital, Lausanne, SwitzerlandDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesInstitute of Pathology, Department of Laboratory Medicine and Pathology, CHUV University Hospital, Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandAlgoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON, CanadaDivision of Clinical Sciences, Section of Internal Medicine, Northern Ontario School of Medicine, Sudbury, ON, CanadaDepartment of Medical Oncology, CHUV University Hospital, Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Medical Oncology, CHUV University Hospital, Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandSarcomas are traditionally considered “cold” tumors with poor response to immunotherapy. However, evidence accumulating over the last years shows that immune checkpoint inhibitors (ICIs) may have a role in selected sarcoma patients according to predictive markers. Here, we report the case of a woman diagnosed with a primary cardiac undifferentiated sarcoma. Following failure of standard first line chemotherapy, high-throughput sequencing (HTS) revealed a high tumor mutational burden (TMB), pathogenic mutations in FAT1 and NOTCH2 and a microsatellite instability (MSI)-associated signature. Immunohistochemistry confirmed mismatch repair-deficiency (MMRd) and abundant CD8+ tumor-infiltrating lymphocytes (TILs), in the absence of tertiary lymphoid structures. The patient was, therefore, treated with the ICI pembrolizumab, reaching a complete response that continues to persist at last follow-up, more than seven years from initial diagnosis and nearly six years from initiation of ICI treatment. This case illustrates the importance of performing HTS in rare sarcomas given the availability of efficient therapies, such as those for tumors displaying high TMB or MMRd/MSI. In agreement with other reports, it supports the contention that MMRd/MSI status and high numbers of TILs are valuable predictive markers of response to immunotherapy in sarcomas.https://www.frontiersin.org/articles/10.3389/fonc.2025.1485386/fullcardiac sarcomaimmune-checkpoint inhibitors (ICI)complete response (CR)predictive markersmismatch repair deficiency (MMRd)microsatellite instability (MSI) |
| spellingShingle | Daniela A. Ferraro Bettina Bisig Bettina Bisig David C. Rotzinger Fresia Pareja Edoardo Missiaglia Edoardo Missiaglia Ioannis Voutsadakis Ioannis Voutsadakis Krisztian Homicsko Krisztian Homicsko Antonia Digklia Antonia Digklia Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization Frontiers in Oncology cardiac sarcoma immune-checkpoint inhibitors (ICI) complete response (CR) predictive markers mismatch repair deficiency (MMRd) microsatellite instability (MSI) |
| title | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization |
| title_full | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization |
| title_fullStr | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization |
| title_full_unstemmed | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization |
| title_short | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization |
| title_sort | case report lasting complete response to pembrolizumab in mismatch repair deficient cardiac sarcoma a genomic characterization |
| topic | cardiac sarcoma immune-checkpoint inhibitors (ICI) complete response (CR) predictive markers mismatch repair deficiency (MMRd) microsatellite instability (MSI) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1485386/full |
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