Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: A genomic characterization Journal Article
| Authors: | Ferraro, D. A.; Bisig, B.; Rotzinger, D. C.; Pareja, F.; Missiaglia, E.; Voutsadakis, I.; Homicsko, K.; Digklia, A. |
| Article Title: | Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: A genomic characterization |
| Abstract: | 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. Copyright © 2025 Ferraro, Bisig, Rotzinger, Pareja, Missiaglia, Voutsadakis, Homicsko and Digklia. |
| Keywords: | immunohistochemistry; adult; clinical article; treatment response; aged; gene mutation; somatic mutation; frameshift mutation; missense mutation; case report; doxorubicin; nuclear magnetic resonance imaging; genetic analysis; tumor associated leukocyte; cancer immunotherapy; computer assisted tomography; gene amplification; cell infiltration; histology; immunotherapy; mismatch repair; microsatellite instability; hydrocortisone; inferior cava vein; pyrosequencing; notch2 receptor; adrenal insufficiency; olaratumab; superior cava vein; immune checkpoint inhibitor; high throughput sequencing; human; female; article; pembrolizumab; heart sarcoma; predictive markers; microsatellite instability (msi); positron emission tomography-computed tomography; cardiac sarcoma; tumor mutational burden; complete response (cr); immune-checkpoint inhibitors (ici); mismatch repair deficiency (mmrd) |
| Journal Title: | Frontiers in Oncology |
| Volume: | 15 |
| ISSN: | 2234-943X |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2025-04-03 |
| Start Page: | 1485386 |
| Language: | English |
| DOI: | 10.3389/fonc.2025.1485386 |
| PROVIDER: | scopus |
| PMCID: | PMC12003144 |
| PUBMED: | 40248199 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
