The Role of MSI Testing Methodology and Its Heterogeneity in Predicting Colorectal Cancer Immunotherapy Response Article Swipe
Alexandra Lebedeva
,
Anastasiia Taraskina
,
Tatiana Grigoreva
,
Ekaterina Belova
,
Olesya Kuznetsova
,
D.A. Kravchuk
,
A. N. Sergeeva
,
Alexandra Kavun
,
Egor Veselovsky
,
Vladislav Nikulin
,
Saida Aliyarova
,
Laima Belyaeva
,
A. Tryakin
,
М. Yu. Fedyanin
,
Vladislav Mileyko
,
Maxim Ivanov
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms26073420
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms26073420
MSI is a crucial biomarker for selecting CRC patients for immunotherapy. Here, we analyze the first results from the observational prospective trial BLOOMSI (NCT06414304), which investigated the impact of MSI/dMMR testing methods and baseline tumor heterogeneity on treatment outcomes. Thirty MSI/dMMR+ CRC patients, who were candidates for immunotherapy, were enrolled. Depending on the local test used for MSI/dMMR, central PCR/IHC was performed. Baseline FFPE and liquid biopsy (LB) were analyzed with NGS. ORR (objective response rate) in the ITT population was 50% (95% CI, 31.3–68.7%). Concordance between local/central dMMR/MSI testing was 81%, and the concordance of IHC, PCR, NGS/FFPE, and NGS/LB was 68.4%. The ORR was similar for IHC+, PCR+, NGS/FFPE+, and NGS/LB+ patients (55.6%, 55.6%, 55%, and 57.9%, respectively). The ORR among patients with discordant IHC/PCR results was 0%, and the ORR among patients with NGS/LB-ORR was 25% (2/8 CR). Next, we performed quantitative MSI analysis, reflecting the clonality of MSI+ tumor cells. Multivariate analysis identified MSI clonality in FFPE (HR 0.63, 95% CI, 0.39–0.99, p = 0.0487) and LB (HR 3.05, 95% CI, 2.01–4.65, p < 0.00001) as independent predictors of progression. The ORR in patients with high clonality (≥7%, n = 4, NGS/LB) was 25%. We describe baseline methodological predictors of non-response to immunotherapy and propose a strategy for selecting potential non-responders. These findings warrant further investigation.
Related Topics
Concepts
Concordance
Medicine
Microsatellite instability
Internal medicine
Oncology
Colorectal cancer
Immunotherapy
Biomarker
Population
Cancer
Biology
Microsatellite
Gene
Genetics
Allele
Environmental health
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms26073420
- https://www.mdpi.com/1422-0067/26/7/3420/pdf?version=1743849855
- OA Status
- gold
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409567837
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409567837Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms26073420Digital Object Identifier
- Title
-
The Role of MSI Testing Methodology and Its Heterogeneity in Predicting Colorectal Cancer Immunotherapy ResponseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-04-05Full publication date if available
- Authors
-
Alexandra Lebedeva, Anastasiia Taraskina, Tatiana Grigoreva, Ekaterina Belova, Olesya Kuznetsova, D.A. Kravchuk, A. N. Sergeeva, Alexandra Kavun, Egor Veselovsky, Vladislav Nikulin, Saida Aliyarova, Laima Belyaeva, A. Tryakin, М. Yu. Fedyanin, Vladislav Mileyko, Maxim IvanovList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms26073420Publisher landing page
- PDF URL
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https://www.mdpi.com/1422-0067/26/7/3420/pdf?version=1743849855Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/1422-0067/26/7/3420/pdf?version=1743849855Direct OA link when available
- Concepts
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Concordance, Medicine, Microsatellite instability, Internal medicine, Oncology, Colorectal cancer, Immunotherapy, Biomarker, Population, Cancer, Biology, Microsatellite, Gene, Genetics, Allele, Environmental healthTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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48Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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