Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers
Abstract Background Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these “cold tumors”. In clinical practice, when tTMB is not availab...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s43856-024-00687-5 |
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| author | Reagan M. Barnett Albert Jang Sree Lanka PIngfu Fu Leslie A. Bucheit Hani Babiker Alan Bryce Haley M. Meyer Yujin Choi Casey Moore Rohan Garje Xin Gao Dae Won Kim Richard Y. Chang Pat Gulhati Ryne Ramaker Rani Bansal Tian Zhang A. Oliver Sartor Andrew J. Armstrong Mehmet A. Bilen Pedro Barata |
| author_facet | Reagan M. Barnett Albert Jang Sree Lanka PIngfu Fu Leslie A. Bucheit Hani Babiker Alan Bryce Haley M. Meyer Yujin Choi Casey Moore Rohan Garje Xin Gao Dae Won Kim Richard Y. Chang Pat Gulhati Ryne Ramaker Rani Bansal Tian Zhang A. Oliver Sartor Andrew J. Armstrong Mehmet A. Bilen Pedro Barata |
| author_sort | Reagan M. Barnett |
| collection | DOAJ |
| description | Abstract Background Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these “cold tumors”. In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs. Methods This retrospective, real-world study included a final cohort of metastatic breast and prostate cancer patients treated with an ICI following a liquid biopsy test. Multiple bTMB-High cut-offs were assessed. Clinical, genomic, and outcomes data were collected. We hypothesized that a cut-off of bTMB ≥10 mut/Mb is not a strong predictor of response to ICIs in this setting. The Guardant Health genomic database (GHGD) was then queried (N = 13,992) for associations of bTMB with genomic alterations. Results In the clinical cohort (N = 48), ICI treatment is offered after a median of 3 (1–9) lines of treatment. The median bTMB is 16.4 (10–186) mut/Mb. The median time on ICI and PFS is 2.1 (0–1.7) and 3.1 months (95%CI, 1.6–4.6) respectively; no difference by MSI/MMR status (p = 0.152). Response rate among eligible patients (n = 36) is 16.7%; only N = 1/6 in bTMB <16 mut/Mb. High bMSI is associated with higher bTMB (correlation test, r = 0.66, p = 0.000). In the GHGD, patients with bTMB high have significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes. Conclusions In this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers. |
| format | Article |
| id | doaj-art-bec170d452674488b50867efdc8a48c0 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-bec170d452674488b50867efdc8a48c02024-12-08T12:44:22ZengNature PortfolioCommunications Medicine2730-664X2024-12-01411710.1038/s43856-024-00687-5Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancersReagan M. Barnett0Albert Jang1Sree Lanka2PIngfu Fu3Leslie A. Bucheit4Hani Babiker5Alan Bryce6Haley M. Meyer7Yujin Choi8Casey Moore9Rohan Garje10Xin Gao11Dae Won Kim12Richard Y. Chang13Pat Gulhati14Ryne Ramaker15Rani Bansal16Tian Zhang17A. Oliver Sartor18Andrew J. Armstrong19Mehmet A. Bilen20Pedro Barata21Guardant Health, Inc, Palo AltoUniversity Hospitals Seidman Cancer CenterTulane Cancer CenterUniversity Hospitals Seidman Cancer CenterGuardant Health, Inc, Palo AltoMayo Clinic JacksonvilleMayo Clinic PhoenixMayo Clinic PhoenixEmory UniversityUT Southwestern UniversityMiami Cancer Institute Baptist HealthMassachuesetts General Hospital Cancer CenterMoffitt Cancer InstituteUniversity Hospitals Seidman Cancer CenterRutgers UniversityMayo ClinicMayo ClinicUT Southwestern UniversityMayo ClinicDuke Cancer Institute Center for Prostate and Urologic Cancers, Duke UniversityEmory UniversityUniversity Hospitals Seidman Cancer CenterAbstract Background Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these “cold tumors”. In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs. Methods This retrospective, real-world study included a final cohort of metastatic breast and prostate cancer patients treated with an ICI following a liquid biopsy test. Multiple bTMB-High cut-offs were assessed. Clinical, genomic, and outcomes data were collected. We hypothesized that a cut-off of bTMB ≥10 mut/Mb is not a strong predictor of response to ICIs in this setting. The Guardant Health genomic database (GHGD) was then queried (N = 13,992) for associations of bTMB with genomic alterations. Results In the clinical cohort (N = 48), ICI treatment is offered after a median of 3 (1–9) lines of treatment. The median bTMB is 16.4 (10–186) mut/Mb. The median time on ICI and PFS is 2.1 (0–1.7) and 3.1 months (95%CI, 1.6–4.6) respectively; no difference by MSI/MMR status (p = 0.152). Response rate among eligible patients (n = 36) is 16.7%; only N = 1/6 in bTMB <16 mut/Mb. High bMSI is associated with higher bTMB (correlation test, r = 0.66, p = 0.000). In the GHGD, patients with bTMB high have significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes. Conclusions In this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers.https://doi.org/10.1038/s43856-024-00687-5 |
| spellingShingle | Reagan M. Barnett Albert Jang Sree Lanka PIngfu Fu Leslie A. Bucheit Hani Babiker Alan Bryce Haley M. Meyer Yujin Choi Casey Moore Rohan Garje Xin Gao Dae Won Kim Richard Y. Chang Pat Gulhati Ryne Ramaker Rani Bansal Tian Zhang A. Oliver Sartor Andrew J. Armstrong Mehmet A. Bilen Pedro Barata Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers Communications Medicine |
| title | Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| title_full | Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| title_fullStr | Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| title_full_unstemmed | Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| title_short | Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| title_sort | blood based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers |
| url | https://doi.org/10.1038/s43856-024-00687-5 |
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