Abstract 3862
Background
The role of tumour mutation burden (TMB) as predictive biomarker of response to immune checkpoint inhibitors (ICI) is being explored in colorectal cancer (CRC). Microsatellite instability status (MSI) is currently used to identify CRC patients who may benefit from ICI. However, TMB values vary significantly among MSI CRC. In addition, selected microsatellite stable (MSS) with high TMB might also benefit treatment with ICI.
Methods
TMB evaluation was performed with the Oncomine Tumor Mutation Load Assay (OTML, Thermofisher) on the Ion S5XL platform. Data analysis was carried out using Ion Reporter Software v5.10. TMB was calculated as the total number of non-synonymous somatic single nucleotide variants (SNVs) and indels divided by number of bases sequenced. MSI status was analysed by means of the Idylla MSI assay (Biocartis), which evaluates the presence of mutations in 7 novel MSI loci.
Results
TMB analysis was performed on 106 formalin-fixed paraffin embedded CRC samples and the data were compared with the MSI results. The Idylla assay classified 68 samples as MSS and 38 samples as microsatellite instable (MSI-H). The TMB values ranged from zero to 21.22 (median: 5.005) in the MSS and from 13.42 to 204.8 in the MSI-H group (median: 25.66), with a significant difference in median values (P < 0.0001). A significant difference in TMB values was also observed when the number of mutated MSI-associated loci was ≥2 versus <2. We next correlated the presence of mutations in a group of driver genes with the TMB values. Significantly different median TMB values were registered when a BRAF (Mann Whitney p value: 0.0023) or PIK3CA mutation (p value: 0.0082) was present, but not when KRAS alterations were detected.
Conclusions
The TMB values assessed with the OTML assay strongly correlated with MSI status in CRC. However, significant heterogeneity in TMB levels were detected among both MSI and MSS tumors, suggesting that TMB testing might provide additional information on sensitivity to ICI in CRC. The correlations with driver gene alterations might help in selecting tumors to be tested for TMB.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4506 - Single intravenous preoperative administration of the oncolytic virus Pexa-Vec to prime anti-tumor immunity
Presenter: Adel Samson
Session: Poster Display session 3
Resources:
Abstract
1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients
Presenter: Shinichi Kageyama
Session: Poster Display session 3
Resources:
Abstract
4244 - T cell repertoire sequencing reveals dynamics of response to dendritic cell vaccine plus dasatinib for checkpoint blockade resistant metastatic melanoma
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
5791 - Ixovex, a novel oncolytic E1B-mutated adenovirus
Presenter: Mohiemen Anwar
Session: Poster Display session 3
Resources:
Abstract
4170 - Anti-CSPG4 DNA vaccination as a promising strategy for the treatment of CSPG4+ tumors: a comparative oncology trial
Presenter: Federica Riccardo
Session: Poster Display session 3
Resources:
Abstract
5780 - Antitumor activity, immunogenicity and safety of a novel PD-1 vaccine in combination with two chimeric HER-2 peptide vaccine in syngeneic Balb/c, C57Bl/6 models and in beagle dogs
Presenter: Pravin Kaumaya
Session: Poster Display session 3
Resources:
Abstract
5860 - Maternal immunization against ALK as a weapon to fight neuroblastoma
Presenter: Giuseppina Barutello
Session: Poster Display session 3
Resources:
Abstract
4720 - Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumors
Presenter: Jason Luke
Session: Poster Display session 3
Resources:
Abstract
5717 - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumors leading to tumor inhibition and memory responses
Presenter: Stella Martomo
Session: Poster Display session 3
Resources:
Abstract
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract