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.
This dataset included 33 childhood B-cell precursor (BCP) acute lymphoblastic leukemia Micro-C samples. All samples were subjected to Illumina pair-end sequencing.
This dataset contains whole exome sequencing data of 13 family members of 5 heritable pulmonary arterial hypertension families.
This dataset contains WGBS of a stepwise-edited, human melanoma model including in vitro samples and corresponding xenografts.
This dataset contains single cell RNA-sequencing of EAC samples by 10x Genomics. Total number of files - 24. File format - FASTQ.
This dataset contains single cell RNA-sequencing of BE samples by 10x Genomics. Total number of files - 28. File format - FASTQ.
This dataset includes 19 bamfiles of tumor, relapsed tumor and normal samples derived from 7 patients.
This dataset contains 21 pediatric brain tumor cases which where obtained during surgery using a cavitating ultrasonic aspiration and submitted to nanopore whole genome sequencing.
This dataset includes 66 RNA sequences datasets of mesothelioma explants under three conditions: baseline, untreated control and thiostrepton treatment.
This dataset includes 2*76bp RNA-seq reads from 9 pigs sequenced using Illumina NextSeq500.
