Abstract 6127
Background
Tumor mutation burden (TMB) and T cell receptor (TCR) diversity have been suggested as predictive biomarkers in cancer immunotherapy. It is not clear how chemotherapy influences TMB, and how TMB or clinical factors correlate with TCR clonality. The aim of this study is to investigate the relationship between TMB and TCR clonality and to provide suggestions for patient selection and the opportunity to start immunotherapy in East Asian late-stage lung cancer patients with first-line chemotherapy.
Methods
43 NSCLC patients and 18 SCLC patients with no TKI-related driver gene (EGFR, ALK, ROS1, RET, BRAF, C-MET) mutations were enrolled in this study. Genomic variations and TMB were determined with lung cancer tissue by whole-exome sequencing (WES). TCR sequencing was also performed with peripheral blood samples. Sequencing data were analyzed with R packages and statistics analysis was performed with SPSS 20 software. P ≤ 0.05 was regarded as statistically significant.
Results
The mutation spectrums were changed dramatically after chemotherapy in NSCLC patients. Chemotherapy appeared to cause decreases in the positive detection rate of mutated genes. Significant decrease in TMB from mean value of 3.67 to 1.95 were observed after chemotherapy in these NSCLC patients (p = 0.05), and patients can be dichotomized based on TMB decrease extent. The relationship between TCR clonality and TMB or clinical factors were also explored in NSCLC and SCLC patients. The number of TCR clones was not correlated with TMB, gender, age, metastasis, lung cancer subtype or therapeutic response (p > 0.05). However, it was dramatically higher in patients with smoking history than those with no smoking history (p = 0.01).
Conclusions
This study suggested that chemotherapy could alter the genomic profiles and TMB dramatically. Patients with decreased TMB after the first-line chemotherapy may be less likely to benefit from immunotherapy. Non-smokers with higher TCR diversity than smokers may be more likely to benefit from immunotherapy. Since the number of TCR clones was not correlated with TMB, it is still worth investigating whether TMB or TCR clonality, or both combined is a better predictive biomarker for immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was supported in part by a grant from National Natural Science Foundation of China (81802255), Shanghai Pujiang Program (17PJD036) and a grant from Shanghai Municipal Commission of Health and Family Planning Program (20174Y0131). National key research & development project (2016YFC0902300). Major disease clinical skills enhancement program of three-year action plan for promoting clinical skills and clinical innovation in municipal hospitals, Shanghai Shen Kang Hospital Development Center Clinical Research Plan of SHDC (16CR1001A). The fundamental research funds for the central universities.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract