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
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract