Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization

Daniela A. Ferraro; Bettina Bisig; David C. Rotzinger; Fresia Pareja; Edoardo Missiaglia; Ioannis Voutsadakis; Krisztian Homicsko; Antonia Digklia

doi:10.3389/fonc.2025.1485386

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Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization

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Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization

Daniela A. Ferraro, Bettina Bisig, David C. Rotzinger, Fresia Pareja, Edoardo Missiaglia, Ioannis Voutsadakis, Krisztian Homicsko and Antonia Digklia

Frontiers in oncology, Vol.15, 1485386

04/01/2025

DOI: 10.3389/fonc.2025.1485386

PMCID: PMC12003144

PMID: 40248199

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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.

cardiac sarcoma

complete response (CR)

immune-checkpoint inhibitors (ICI)

microsatellite instability (MSI)

mismatch repair deficiency (MMRd)

predictive markers

Details

Title: Subtitle: Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization
Creators: Daniela A. Ferraro - University Hospital of Lausanne
Bettina Bisig - University Hospital of Lausanne
David C. Rotzinger - University Hospital of Lausanne
Fresia Pareja - Memorial Sloan Kettering Cancer Center
Edoardo Missiaglia - University Hospital of Lausanne
Ioannis Voutsadakis - NOSM University
Krisztian Homicsko - University Hospital of Lausanne
Antonia Digklia - University Hospital of Lausanne
Resource Type: Journal article
Publication Details: Frontiers in oncology, Vol.15, 1485386
DOI: 10.3389/fonc.2025.1485386
PMID: 40248199
PMCID: PMC12003144
NLM abbreviation: Front Oncol
ISSN: 2234-943X
eISSN: 2234-943X
Publisher: Frontiers Media S.A
Grant note: NIH/NCI: P50 CA24779 01 Cancer Center Support Grant of the NIH/NCI: P30CA008748
The author(s) declare that financial support was received for the research and/or publication of this article. F.P. is partially funded by an NIH/NCI P50 CA24779 01 grant. This work as supported in part by a Cancer Center Support Grant of the NIH/NCI (P30CA008748; MSK).
Language: English
Date published: 04/01/2025
Academic Unit: Internal Medicine
Record Identifier: 9984808214602771

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