In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients
Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urg...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1271 |
| _version_ | 1797762718405492736 |
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| author | Simon Heeke Jonathan Benzaquen Elodie Long-Mira Benoit Audelan Virginie Lespinet Olivier Bordone Salomé Lalvée Katia Zahaf Michel Poudenx Olivier Humbert Henri Montaudié Pierre-Michel Dugourd Madleen Chassang Thierry Passeron Hervé Delingette Charles-Hugo Marquette Véronique Hofman Albrecht Stenzinger Marius Ilié Paul Hofman |
| author_facet | Simon Heeke Jonathan Benzaquen Elodie Long-Mira Benoit Audelan Virginie Lespinet Olivier Bordone Salomé Lalvée Katia Zahaf Michel Poudenx Olivier Humbert Henri Montaudié Pierre-Michel Dugourd Madleen Chassang Thierry Passeron Hervé Delingette Charles-Hugo Marquette Véronique Hofman Albrecht Stenzinger Marius Ilié Paul Hofman |
| author_sort | Simon Heeke |
| collection | DOAJ |
| description | Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (<i>R</i><sup>2</sup> = 0.73) and melanoma (<i>R</i><sup>2</sup><i> </i>= 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC. |
| first_indexed | 2024-03-12T19:31:25Z |
| format | Article |
| id | doaj.art-44b397a93c0349328bac1c59198b2401 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:31:25Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-44b397a93c0349328bac1c59198b24012023-08-02T04:27:17ZengMDPI AGCancers2072-66942019-08-01119127110.3390/cancers11091271cancers11091271In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma PatientsSimon Heeke0Jonathan Benzaquen1Elodie Long-Mira2Benoit Audelan3Virginie Lespinet4Olivier Bordone5Salomé Lalvée6Katia Zahaf7Michel Poudenx8Olivier Humbert9Henri Montaudié10Pierre-Michel Dugourd11Madleen Chassang12Thierry Passeron13Hervé Delingette14Charles-Hugo Marquette15Véronique Hofman16Albrecht Stenzinger17Marius Ilié18Paul Hofman19Université Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, GermanyUniversité Côte d’Azur, 06000 Nice, FranceUniversité Côte d’Azur, 06000 Nice, FranceTumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (<i>R</i><sup>2</sup> = 0.73) and melanoma (<i>R</i><sup>2</sup><i> </i>= 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC.https://www.mdpi.com/2072-6694/11/9/1271tumor mutational burdenFoundationOne assayOncomine TML assaylung cancermelanomaimmunotherapy |
| spellingShingle | Simon Heeke Jonathan Benzaquen Elodie Long-Mira Benoit Audelan Virginie Lespinet Olivier Bordone Salomé Lalvée Katia Zahaf Michel Poudenx Olivier Humbert Henri Montaudié Pierre-Michel Dugourd Madleen Chassang Thierry Passeron Hervé Delingette Charles-Hugo Marquette Véronique Hofman Albrecht Stenzinger Marius Ilié Paul Hofman In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients Cancers tumor mutational burden FoundationOne assay Oncomine TML assay lung cancer melanoma immunotherapy |
| title | In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients |
| title_full | In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients |
| title_fullStr | In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients |
| title_full_unstemmed | In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients |
| title_short | In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients |
| title_sort | in house implementation of tumor mutational burden testing to predict durable clinical benefit in non small cell lung cancer and melanoma patients |
| topic | tumor mutational burden FoundationOne assay Oncomine TML assay lung cancer melanoma immunotherapy |
| url | https://www.mdpi.com/2072-6694/11/9/1271 |
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