High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis
Background Tumor mutation burden (TMB) is an important biomarker to predict response to anti-PD-L1 treatment across cancer types. TruSight Oncology 500 (TSO500) is currently used globally as a routine assay for TMB.Methods Between 2019 and 2021, 1744 patients with cancer received TSO500 assay as par...
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BMJ Publishing Group
2023-04-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/4/e006454.full |
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| author | Sehhoon Park Jaeyun Jung You Jeong Heo |
| author_facet | Sehhoon Park Jaeyun Jung You Jeong Heo |
| author_sort | Sehhoon Park |
| collection | DOAJ |
| description | Background Tumor mutation burden (TMB) is an important biomarker to predict response to anti-PD-L1 treatment across cancer types. TruSight Oncology 500 (TSO500) is currently used globally as a routine assay for TMB.Methods Between 2019 and 2021, 1744 patients with cancer received TSO500 assay as part of a real-world clinical practice at the Samsung Medical Center, and 426 received anti-PD-(L)1 treatment. Correlations between TMB and clinical outcomes of anti-PD-(L)1 were analyzed. Digital spatial profiling (DSP) was used to investigate the tumor immune environment’s influence on the treatment response to anti-PD-(L)1 in high TMB (TMB-H) patients (n=8).Results The incidence of TMB-H (≥10 mutations (mt)/megabase (Mb)) was 14.7% (n=257). Among TMB-H patients, the most common cancer type was colorectal cancer (n=108, 42.0%), followed by gastric cancer (GC; n=49, 19.1%), bladder cancer (n=21, 8.2%), cholangiocarcinoma (n=21, 8.2%), non-small cell lung cancer (n=17, 6.6%), melanoma (n=8, 3.1%), gallbladder cancer (GBC; n=7, 2.7%), and others (n=26, 10.1%). The response rate to anti-PD-(L)1 therapy was substantially higher in GC (71.4% vs 25.8%), GBC (50.0% vs 12.5%), head and neck cancer (50.0% vs 11.1%), and melanoma (71.4% vs 50.7%) among TMB-H patients when compared with low TMB (TMB-L) (<10 mt/Mb) patients with statistical significance. Additional analysis of patients with TMB ≥16 mt/Mb demonstrated prolonged survival after anti-PD-(L)1 therapy compared with patients with TMB-L (not reached vs 418 days, p=0.03). The benefit of TMB ≥16 mt/Mb was greater when combined with microsatellite status and PD-L1 expression profiles. Among the TMB-H patients, those who responded to anti-PD-L1 therapy had numerous active immune cells that infiltrated the tumor regions during the DSP analysis. Natural killer cells (p=0.04), cytotoxic T cells (p<0.01), memory T cells (p<0.01), naïve memory T cells (p<0.01), and proteins related to T-cell proliferation (p<0.01) were observed in a responder group compared with a non-responder group. In contrast, exhausted T-cell and M2 macrophage counts were increased in the non-responder group.Conclusions The overall incidence of TMB status was analyzed by the TSO500 assay, and TMB-H was observed in 14.7% of the pan-cancer population. In a real-world setting, TMB-H identified by a target sequencing panel seemed to predict response to anti-PD-(L)1 therapy, especially in patients with a higher proportion of immune cells enriched in the tumor region. |
| format | Article |
| id | doaj-art-6b71b29021a6420a9546819f70b0d8b5 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-6b71b29021a6420a9546819f70b0d8b52025-02-02T11:55:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-04-0111410.1136/jitc-2022-006454High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysisSehhoon Park0Jaeyun Jung1You Jeong Heo23 Division of Hematology-Oncology, Samsung Medical Center, Gangnam-gu, Seoul, Korea (the Republic of)Innovative Institute for Precision Medicine, Samsung Medical Center, Seoul, Korea (the Republic of)Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Seoul, Gangnam-gu, Korea (the Republic of)Background Tumor mutation burden (TMB) is an important biomarker to predict response to anti-PD-L1 treatment across cancer types. TruSight Oncology 500 (TSO500) is currently used globally as a routine assay for TMB.Methods Between 2019 and 2021, 1744 patients with cancer received TSO500 assay as part of a real-world clinical practice at the Samsung Medical Center, and 426 received anti-PD-(L)1 treatment. Correlations between TMB and clinical outcomes of anti-PD-(L)1 were analyzed. Digital spatial profiling (DSP) was used to investigate the tumor immune environment’s influence on the treatment response to anti-PD-(L)1 in high TMB (TMB-H) patients (n=8).Results The incidence of TMB-H (≥10 mutations (mt)/megabase (Mb)) was 14.7% (n=257). Among TMB-H patients, the most common cancer type was colorectal cancer (n=108, 42.0%), followed by gastric cancer (GC; n=49, 19.1%), bladder cancer (n=21, 8.2%), cholangiocarcinoma (n=21, 8.2%), non-small cell lung cancer (n=17, 6.6%), melanoma (n=8, 3.1%), gallbladder cancer (GBC; n=7, 2.7%), and others (n=26, 10.1%). The response rate to anti-PD-(L)1 therapy was substantially higher in GC (71.4% vs 25.8%), GBC (50.0% vs 12.5%), head and neck cancer (50.0% vs 11.1%), and melanoma (71.4% vs 50.7%) among TMB-H patients when compared with low TMB (TMB-L) (<10 mt/Mb) patients with statistical significance. Additional analysis of patients with TMB ≥16 mt/Mb demonstrated prolonged survival after anti-PD-(L)1 therapy compared with patients with TMB-L (not reached vs 418 days, p=0.03). The benefit of TMB ≥16 mt/Mb was greater when combined with microsatellite status and PD-L1 expression profiles. Among the TMB-H patients, those who responded to anti-PD-L1 therapy had numerous active immune cells that infiltrated the tumor regions during the DSP analysis. Natural killer cells (p=0.04), cytotoxic T cells (p<0.01), memory T cells (p<0.01), naïve memory T cells (p<0.01), and proteins related to T-cell proliferation (p<0.01) were observed in a responder group compared with a non-responder group. In contrast, exhausted T-cell and M2 macrophage counts were increased in the non-responder group.Conclusions The overall incidence of TMB status was analyzed by the TSO500 assay, and TMB-H was observed in 14.7% of the pan-cancer population. In a real-world setting, TMB-H identified by a target sequencing panel seemed to predict response to anti-PD-(L)1 therapy, especially in patients with a higher proportion of immune cells enriched in the tumor region.https://jitc.bmj.com/content/11/4/e006454.full |
| spellingShingle | Sehhoon Park Jaeyun Jung You Jeong Heo High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis Journal for ImmunoTherapy of Cancer |
| title | High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis |
| title_full | High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis |
| title_fullStr | High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis |
| title_full_unstemmed | High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis |
| title_short | High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis |
| title_sort | high tumor mutational burden predicts favorable response to anti pd l 1 therapy in patients with solid tumor a real world pan tumor analysis |
| url | https://jitc.bmj.com/content/11/4/e006454.full |
| work_keys_str_mv | AT sehhoonpark hightumormutationalburdenpredictsfavorableresponsetoantipdl1therapyinpatientswithsolidtumorarealworldpantumoranalysis AT jaeyunjung hightumormutationalburdenpredictsfavorableresponsetoantipdl1therapyinpatientswithsolidtumorarealworldpantumoranalysis AT youjeongheo hightumormutationalburdenpredictsfavorableresponsetoantipdl1therapyinpatientswithsolidtumorarealworldpantumoranalysis |