Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma - CM066-WES
Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.
- 32 samples
- DAC: EGAC00001001667
- Technology: Illumina HiSeq 2500
- HMB DUO:0000006 (version: 2019-01-07)health or medical or biomedical researchThis data use permission indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry.
- DS DUO:0000007 (version: 2019-01-07)disease specific researchThis data use permission indicates that use is allowed provided it is related to the specified disease.ModifiersMONDO:0004992 MONDO:0005105
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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
| Study ID | Study Title | Study Type |
|---|---|---|
| Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.
| ID | File Type | Size | Located in | |
|---|---|---|---|---|
| EGAF00004186659 | fastq.gz | 4.8 GB | ||
| EGAF00004186660 | fastq.gz | 4.9 GB | ||
| EGAF00004186661 | fastq.gz | 4.0 GB | ||
| EGAF00004186662 | fastq.gz | 4.2 GB | ||
| EGAF00004186663 | fastq.gz | 3.6 GB | ||
| EGAF00004186664 | fastq.gz | 3.8 GB | ||
| EGAF00004186665 | fastq.gz | 3.4 GB | ||
| EGAF00004186666 | fastq.gz | 3.6 GB | ||
| EGAF00004186667 | fastq.gz | 3.2 GB | ||
| EGAF00004186668 | fastq.gz | 3.3 GB | ||
| EGAF00004186669 | fastq.gz | 3.5 GB | ||
| EGAF00004186670 | fastq.gz | 3.6 GB | ||
| EGAF00004186671 | fastq.gz | 3.6 GB | ||
| EGAF00004186672 | fastq.gz | 3.7 GB | ||
| EGAF00004186673 | fastq.gz | 3.8 GB | ||
| EGAF00004186674 | fastq.gz | 3.9 GB | ||
| EGAF00004186675 | fastq.gz | 3.3 GB | ||
| EGAF00004186676 | fastq.gz | 3.3 GB | ||
| EGAF00004186677 | fastq.gz | 4.2 GB | ||
| EGAF00004186678 | fastq.gz | 4.3 GB | ||
| EGAF00004186679 | fastq.gz | 4.3 GB | ||
| EGAF00004186680 | fastq.gz | 4.6 GB | ||
| EGAF00004186681 | fastq.gz | 4.4 GB | ||
| EGAF00004186682 | fastq.gz | 4.3 GB | ||
| EGAF00004186683 | fastq.gz | 3.2 GB | ||
| EGAF00004186684 | fastq.gz | 3.4 GB | ||
| EGAF00004186685 | fastq.gz | 3.2 GB | ||
| EGAF00004186686 | fastq.gz | 3.3 GB | ||
| EGAF00004186687 | fastq.gz | 4.0 GB | ||
| EGAF00004186688 | fastq.gz | 4.0 GB | ||
| EGAF00004186689 | fastq.gz | 3.8 GB | ||
| EGAF00004186690 | fastq.gz | 3.8 GB | ||
| EGAF00004186691 | fastq.gz | 3.9 GB | ||
| EGAF00004186692 | fastq.gz | 4.1 GB | ||
| EGAF00004186693 | fastq.gz | 5.0 GB | ||
| EGAF00004186694 | fastq.gz | 4.8 GB | ||
| EGAF00004186695 | fastq.gz | 4.6 GB | ||
| EGAF00004186696 | fastq.gz | 4.7 GB | ||
| EGAF00004186697 | fastq.gz | 3.4 GB | ||
| EGAF00004186698 | fastq.gz | 3.5 GB | ||
| EGAF00004186699 | fastq.gz | 4.2 GB | ||
| EGAF00004186700 | fastq.gz | 4.3 GB | ||
| EGAF00004186701 | fastq.gz | 3.5 GB | ||
| EGAF00004186702 | fastq.gz | 3.7 GB | ||
| EGAF00004186703 | fastq.gz | 3.7 GB | ||
| EGAF00004186704 | 1620404679683 | 3.9 GB | ||
| EGAF00004186705 | fastq.gz | 4.3 GB | ||
| EGAF00004186706 | fastq.gz | 4.5 GB | ||
| EGAF00004186707 | fastq.gz | 3.4 GB | ||
| EGAF00004186708 | fastq.gz | 3.6 GB | ||
| EGAF00004186709 | fastq.gz | 4.4 GB | ||
| EGAF00004186710 | fastq.gz | 4.5 GB | ||
| EGAF00004186711 | fastq.gz | 3.4 GB | ||
| EGAF00004186712 | fastq.gz | 3.5 GB | ||
| EGAF00004186713 | fastq.gz | 4.7 GB | ||
| EGAF00004186714 | fastq.gz | 4.8 GB | ||
| EGAF00004186715 | fastq.gz | 4.2 GB | ||
| EGAF00004186716 | fastq.gz | 4.4 GB | ||
| EGAF00004186717 | 1620404679684 | 4.4 GB | ||
| EGAF00004186718 | fastq.gz | 4.6 GB | ||
| EGAF00004186719 | fastq.gz | 3.1 GB | ||
| EGAF00004186720 | fastq.gz | 3.4 GB | ||
| EGAF00004186721 | fastq.gz | 4.4 GB | ||
| EGAF00004186722 | fastq.gz | 4.1 GB | ||
| 64 Files (253.3 GB) | ||||