Abstract
Tumor mutational burden (TMB) is a genomic biomarker that predicts favorable responses to immune checkpoint inhibitors (ICIs). Here, we set out to assess the predictive value of TMB on long-term survival outcomes in patients undergoing ICIs. We systematically searched PubMed, Embase, CENTRAL and clinicaltrials.gov from inception to 6 August 2019. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) according to TMB. Data on 5712 patients from 26 studies were included. Among patients who received ICIs, high TMB groups showed better OS (HR 0.53, 95% CI 0.42 to 0.67) and PFS (HR 0.52, 95% CI 0.40 to 0.67) compared to low TMB groups. In patients with high TMB, those who received ICIs had a better OS (HR 0.69, 95% CI 0.50 to 0.95) and PFS (HR = 0.66, 95% CI = 0.47 to 0.92) compared to those who received chemotherapy alone, while in patients with low TMB, such ICI benefits of OS or PFS were not statistically significant. In conclusion, TMB may be an effective biomarker to predict survival in patients undergoing ICI treatment. The role of TMB in identifying patient groups who may benefit from ICIs should be determined in future randomized controlled trials.
Highlights
Cancer immunotherapy using immune checkpoint inhibitors (ICIs) is approved for several malignancies [1,2]
The definition of high and low Tumor mutational burden (TMB) was heterogeneous among the studies
Under a random-effects model, patients in the high TMB group receiving ICIs had significantly increased overall survival (OS) (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.42 to 0.67) and progression-free survival (PFS) (HR 0.52, 95% CI 0.40 to 0.67) compared with patients in the low TMB group (Figures 2 and 3)
Summary
Cancer immunotherapy using immune checkpoint inhibitors (ICIs) is approved for several malignancies [1,2]. Some patients experience significant clinical benefit from ICIs, others. Cancers 2019, 11, 1798 have no or limited clinical benefit [3,4,5], in some cases accompanied by severe side effects. Discovering biomarkers that can identify patients who may benefit from ICIs is crucial. The programmed death-ligand 1 (PD-L1) expression density is widely used and far the only biomarker in clinical routine in various cancer entities. It was approved by the US Food and Drug.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
