Table 1.
Representative recent studies describing the impact of tumor mutation load (TMB) evaluation in the clinical setting
| Type of cancer and stage | No of investigated patients | Test for TMB | Cut-off | Drug/treatment | Results | References |
|---|---|---|---|---|---|---|
| SCLC | 211 (133 Nivo, 78 Nivo + Ipi) | WES | ≥ 248 total mut | Nivolumab, Nivolumab + Ipilimumab | Improved ORR, 1y PFS and 1y OS for TMB high vs. TMB medium and low patients | [21] |
| NSCLC | 34 (16 discovery, 18 validation) | WES | ≥ 178 total mut | Pembrolizumab | Higher TMB was associated with improved objective response, durable clinical benefit and PFS | [20] |
| NSCLC | 312 (158 Nivo, 154 Chemo) | WES | ≥ 243 total mut | Nivolumab vs chemotherapy | High TMB associated with increased ORR and PFS, but not OS | [22] |
| NSCLC | 240 | NGS (49 also with WES) | Anti-PD-(L)1 monotherapy or in combination with anti-CTL-4 |
Elevated TMB improved likelihood of benefit to ICIs Targeted NGS accurately estimates TMB and correlates with WES results |
[30] | |
| Stage IV or recurrent NSCLC | 299, 139 (Nivo + Ipi), 160 (chemotherapy) | NGS | Nivolumab plus ipilimumab, vs. chemotherapy | PFS was longer with first line nivolumab plus ipilimumab than with chemotherapy and a high TMB, irrespective of PD-L1 expression level | [40] | |
| Metastatic melanoma | 65 (32 + 33) | NGS | Nivolumab or pembrolizumab or atezolimumab | Response rate, PFS and OS were superior in high mutation load group | [6] l | |
| Metastatic melanoma | 64 (25 discovery +39 validation) | WES | > 100 total mut | Ipilimumab or tremelimumab | Mutational load is associated with the degree of clinical benefit | [18] |
| CRC | 6004 | Comprehensive Genomic Profiling (CGP) | – | TMB classifies MSI tumors as TMB-high and identifies nearly 3% of CRC as MSS/TMB-high | [27] | |
| CLL | 91 | WES | allo-HSCT | Clinically evident durable remission in patients with neoantigen peptides | [15] | |
| 26 cancer types | 11,348 | NGS and MSI-NGS | – | MSI offers distinct data for treatment decision regarding immune checkpoint inhibitors, in addition to TMB and PD-L1 | [28] | |
| 12 cancer types | 86 | MSI-NGS | Pembrolizumab | Large proportion of mutant neoantigens in MSI cancers make them sensitive to immune checkpoint blockade, regardless the cancer’s tissue of origin | [29] |
NSCLC Non-small cell lung cancer, WES whole-exome sequencing, PFS progression-free survival, OS overall survival, allo-HSCT allo-hematopoietic stem cell transplantation, TILs tumor-infiltrating lymphocytes, MSI microsatellite instability, ICIs immune checkpoint inhibitors