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

cancers

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 (R2 = 0.73) and melanoma (R2 = 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 di erences 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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