Table 1.
Characteristics of studies included in the meta-analysis of the high tumor mutational burden (TMB) group versus low TMB group.
| Study | Type of Study | Malignancy | Type of Immunotherapy | Sample Source | Detection Method | TMB Cutoff | Median TMB (range) | Number of Patients (High/Low TMB) | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Balar et al. 2017 [44] | Retrospective analysis of clinical trial | Urothelial carcinoma | Atezolizumab | Tumor | FoundationOne | ≥16/MB | 8.1 (0.9–62.2) | 97 (NR) | OS |
| Chae et al. 2018 [28] | Retrospective cohort | NSCLC | PD-1/PD-L1 inhibitor | Tumor | FoundationOne | ≥15/MB | 8 (1–55) | 34 (NR) | OS, PFS |
| Chae et al. 2019a [41] | Retrospective cohort | NSCLC | Immune checkpoint inhibitors | Blood | Guardant360 | NR (median) | NR | 20 (10/10) | OS, PFS |
| Chae et al. 2019b [41] | Retrospective cohort | NSCLC | Immune checkpoint inhibitors | Blood | Guardant360 | NR (median) | NR | 12 (6/6) | OS, PFS |
| Cristescu et al. 2018a [30] | Retrospective analysis of clinical trial | Pan-tumor | Pembrolizumab | Tumor | WES | >102.5 | NR | 119 (37/82) | PFS |
| Cristescu et al. 2018b [30] | Retrospective analysis of clinical trial | Melanoma | Pembrolizumab | Tumor | WES | >191.5 | NR | 89 (59/30) | PFS |
| Cristescu et al. 2018c [30] | Retrospective analysis of clinical trial | HNSCC | Pembrolizumab | Tumor | WES | >86 | NR | 107 (54/53) | PFS |
| Fang et al. 2019 [39] | Retrospective analysis of clinical trial | NSCLC | PD-1/PD-L1 inhibitor | Tumor | WES | ≥157 (top tertile) | 87 (4–1528) | 73 (25/48) | PFS |
| Goodman et al. 2017 [27] | Retrospective cohort | Various | Various | Tumor | FoundationOne | ≥20/MB | 6 (1–347) | 151 (38/113) | OS, PFS |
| Hamid et al. 2019 [37] | Retrospective analysis of clinical trial | Melanoma | Atezolizumab | Tumor | FoundationOne | ≥16/MB | NR | 23 (12/11) | OS, PFS |
| Hellmann et al. 2018 [23] | Retrospective analysis of clinical trial | NSCLC | Nivolumab plus ipilimumab | Tumor | WES | >158 (median) | 158 | 75 (37/38) | PFS |
| Hugo et al. 2016 [31] | Retrospective cohort | Melanoma | Pembrolizumab or nivolumab | Tumor | WES | ≥577 (bottom tertile) | 489 (73–3985) | 37 (13/24) | OS |
| Johnson et al. 2016 [29] | Retrospective cohort | Melanoma | PD-1/PD-L1 inhibitor | Tumor | FoundationOne | >23.1/MB | NR | 65 (27/38) | OS, PFS |
| Khagi et al. 2017 [43] | Retrospective cohort | Various | Various | Blood | Guardant360 | >3 total ctDNR alterations | 2 (0–20) | 69 (20/49) | OS, PFS |
| Le et al. 2015 [5] | Clinical trial | Various | Pembrolizumab | Tumor | WES | NR | NR | 15 (NR) | OS, PFS |
| Ricciuti et al. 2019 [40] | Retrospective cohort | Small-cell lung cancer | Immune checkpoint inhibitors | Tumor | NGS (OncoPanel) | >9.7/MB (median) | 9.8 (1.2–31.2) | 52 (26/26) | OS, PFS |
| Rizvi et al. 2015a [22] | Retrospective cohort | NSCLC | Pembrolizumab | Tumor | WES | >209 (median) | NR | 18 (9/9) | PFS |
| Rizvi et al. 2015b [22] | Retrospective cohort | NSCLC | Pembrolizumab | Tumor | WES | >200 (median) | NR | 16 (8/8) | PFS |
| Rizvi et al. 2018 [26] | Retrospective cohort | NSCLC | Immune checkpoint inhibitors | Tumor | WES | >324 | 171 (1–1147) | 49 (12/37) | PFS |
| Roszik et al. 2016 [34] | Retrospective cohort | Melanoma | Ipilimumab | Tumor | NGS | >100 | NR | 76 (57/19) | OS |
| Samstein et al. 2019 [32] | Retrospective cohort | Various | Immune checkpoint inhibitors | Tumor | NGS (MSK-IMPACT) | 90th percentile of each histology | NR | 1662 (NR) | OS |
| Snyder, et al. 2014a [20] | Retrospective cohort | Melanoma | Ipilimumab or tremelimumab | Tumor | WES | >100 | NR | 25 (10/15) | OS |
| Snyder et al. 2014b [20] | Retrospective cohort | Melanoma | Ipilimumab or tremelimumab | Tumor | WES | >100 | NR | 39 (17/22) | OS |
| Van Allen et al. 2015 [21] | Retrospective cohort | Melanoma | Ipilimumab | Tumor | WES | ≥202 (median) | 197 (7–5854) | 110 (55/55) | OS, PFS |
| Wang et al. 2019 [38] | Retrospective analysis of clinical trial | Gastric cancer | Toripalimab | Tumor | WES | ≥12/MB | NR | 54 (12/42) | OS, PFS |
| Yusko et al. 2019a [35] | Retrospective analysis of clinical trial | Melanoma | Nivolumab or ipilimumab | Tumor | WES | NR | 171 | 30 (NR) | OS |
| Yusko et al. 2019b [35] | Retrospective analysis of clinical trial | Melanoma | Nivolumab or ipilimumab | Tumor | WES | NR | 159 | 38 (NR) | OS |
Abbreviations: TMB, tumor mutational burden; NSCLC, non-small cell lung cancer; HNSCC, head and neck squamous cell carcinoma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; WES, whole-exome sequencing; NGS, next-generation sequencing; NR, not reported; OS, overall survival; PFS, progression-free survival.