Table 1 Representative recent studies describing the impact of tumor mutation load (TMB) evaluation in the clinical setting
From: Tumor mutation burden: from comprehensive mutational screening to the clinic
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) | Â | 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 | Â | 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] |