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In-House Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-Small Cell Lung Cancer and Melanoma Patients

Simon Heeke 1, 2, 3, 4 Jonathan Benzaquen 1, 2, 5 Elodie Long-Mira 1, 2, 3, 4 Benoît Audelan 6 Virginie Lespinet 1, 3 Olivier Bordone 1, 3 Salomé Lalvée 1, 3 Katia Zahaf 1, 3 Michel Poudenx 1, 7 Olivier Humbert 1, 8 Henri Montaudié 1, 4, 9 Pierre-Michel Dugourd 1, 9 Madleen Chassang 1, 10 Thierry Passeron 1, 9, 11, 4 Hervé Delingette 6 Charles-Hugo Marquette 1, 2, 3, 4, 5 Véronique Hofman 1, 2, 3, 4 Albrecht Stenzinger 12, 13 Marius Ilié 1, 2, 3, 4 Paul Hofman 1, 2, 3, 4
Abstract : 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 (R 2 = 0.73) and melanoma (R 2 = 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.
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Submitted on : Tuesday, November 26, 2019 - 3:05:19 PM
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Simon Heeke, Jonathan Benzaquen, Elodie Long-Mira, Benoît Audelan, Virginie Lespinet, et al.. In-House Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-Small Cell Lung Cancer and Melanoma Patients. Cancers, MDPI, 2019, 11, ⟨10.3390/cancers11091271⟩. ⟨hal-02381188⟩

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