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Clinical and Molecular Variables Associated With Early Progression to Checkpoint Inhibitors in MSI-High Metastatic
L Hulst1, S Cappuyns1, F Peeters1
1Department of Gastro-enterology and Hepatology, Digestive Oncology, University Hospitals Leuven (UZ Leuven), Leuven, Belgium.
Clinical Colorectal Cancer
|August 3, 2024
Summary
Immune checkpoint inhibitors (ICI) show varied efficacy in deficient mismatch repair/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC). Lower neutrophil-to-lymphocyte ratio and immune-related adverse events predict better overall survival.
Area of Science:
- Oncology
- Immunotherapy
- Colorectal Cancer Research
Background:
- A significant portion of patients with dMMR/MSI-H mCRC exhibit primary resistance or early progression to ICI therapy.
- Conversely, some patients achieve durable responses to ICI treatment, highlighting the need to identify predictive biomarkers.
Purpose of the Study:
- To identify clinical and pathological variables associated with improved overall survival (OS) in patients with dMMR/MSI-H mCRC treated with ICI.
- To determine factors linked to early disease progression (within 12 months) in this patient cohort.
Main Methods:
- Retrospective analysis of 84 patients with dMMR/MSI-H mCRC treated with ICI between 2014 and 2022.
- Kaplan-Meier method for OS estimation.
- Univariate and multivariate Cox and logistic regression analyses to identify predictors of OS and early progression.
Main Results:
- Median OS was 80 months.
- Improved OS was associated with a lower neutrophil-to-lymphocyte ratio (NLR) and the presence of immune-related adverse events (irAEs).
- Early progression was linked to poor performance status, elevated C-reactive protein (CRP) levels, and absence of irAEs.
Conclusions:
- Disease progression is infrequent in dMMR/MSI-H mCRC patients who achieve disease control for at least 12 months.
- Performance status, irAEs, CRP, CEA levels, and NLR are valuable indicators for predicting ICI treatment benefit and guiding clinical decisions.
