Analysis of age, tumor-sidedness, and mismatch repair (MMR) gene with response to immune checkpoint inhibitors (ICIs) in MMR-deficient (dMMR) colorectal cancer (CRC) patients (pts): A multi-institutional study Open Access
Jiang, Weiyi (Spring 2020)
Abstract
Background: ICIs induce durable responses in dMMR CRC pts, overall response rate (ORR) 30-50%. Even though the loss of any MMR gene expression is predictive of responsiveness to ICIs, it is unknown if ORRs are similar across all MMR genes (MLH1, PMS, MSH2, and MSH6). In this study, we analyzed the impact of each specific MMR gene loss and clinical characteristics of patients with best response to ICIs.
Methods: Pts were eligible if they had confirmed dMMR CRC by IHC or microsatellite instability-high (MSI-H) by PCR, and received ICIs between 01/01/2012 and 10/01/2018 at Winship Cancer Institute of Emory University, Mayo Clinic and Vanderbilt University Medical Center. Due to the pattern of frequent concurrent loss and functional dependency, the groups were categorized as MLH1 ±PMS2 vs MSH2 ±MSH6. Cox proportional hazard model and Fisher’s exact test were used for the best response and the distribution of variable among the subgroups. The study was approved by IRB.
Results: A total of 66 pts with dMMR CRC were identified. Overall response rates in MLH1 ±PMS2 and MSH2 ±MSH6 groups were 64.1% and 33.33% respectively without statistical difference (Table). Pts who are 50-65 years old had better ORRs compared to pts with age<50 and >65 (41.46%, 34.15%and 24.39% respectively, P=0.277). Left-sided tumors had a trend toward higher ORRs compared to right-sided tumors (68.29% vs 31.71% P=0.157). Gender and BRAF status were not predictors of response. BRAF mutations were more common in right-sided tumors (26.47% vs 8.33% respectively) and in older patients.
Conclusion: Our data suggests that age 50-65 have improved ORR, and there is a trend for improved ORR for left-sided tumors treated with ICIs in MSI-H CRC pts.
Table of Contents
Table of Contents
Introduction..................................................................................................................................
1 Method ......................................................................................................................................... 3
2.1 Data Collection ...................................................................................................................... 3
2.2 Statistical Analysis Method ................................................................................................... 4
2.2.1 Descriptive analysis ........................................................................................................ 4
2.2.2 Univariate analysis.......................................................................................................... 4
2.2.3 Univariate survival analysis ............................................................................................ 5
3.Result ........................................................................................................................................... 5
3.1 Descriptive analysis ............................................................................................................... 5
3.2 Univariate analysis................................................................................................................. 6
3.3 Univariate survival analysis ................................................................................................... 7
4.Discussion .................................................................................................................................... 7
5.Reference ..................................................................................................................................... 8
6.Appendix.................................................................................................................................... 10
About this Master's Thesis
| School | |
|---|---|
| Department | |
| Subfield / Discipline | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Keyword | |
| Committee Chair / Thesis Advisor |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Analysis of age, tumor-sidedness, and mismatch repair (MMR) gene with response to immune checkpoint inhibitors (ICIs) in MMR-deficient (dMMR) colorectal cancer (CRC) patients (pts): A multi-institutional study () | 2020-04-28 21:27:03 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|