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Ellen Geerdens



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-76 - Tumor Mutational Burden by TSO500 Next Generation Sequencing Panel and Clinical Outcome in Non-Small Cell Lung Cancer (Now Available) (ID 2228)

      10:15 - 18:15  |  Author(s): Ellen Geerdens

      • Abstract
      • Slides

      Background

      High tumor mutational burden (TMB) can predict durable clinical response to treatment with immunotherapy across cancer types. Gold standard to determine TMB, was whole genome sequencing. TMB by targeted next generation sequencing (NGS) has shown to adequately correlate. We describe, as first to our knowledge, correlation between TMB by TSO500 and outcome in NSCLC patients treated with immunotherapy.

      Method

      NSCLC patients treated from 2016 to 2018 with immunotherapy (pembrolizumab or nivolumab in first and further lines) and from whom DNA was readily available after previous routine therapeutic testing, were selected. Finally, 62 patient samples were analyzed with the Illumina TruSight Oncology 500 (TSO500) panel. TMB high was defined as more than 10 mutations/Mb. 22C3 Dako antibody was used for PD-L1 immunohistochemistry. PD-L1 high was defined as 50% or more. Demographic and clinical outcome parameters were collected. A durable response was considered partial or complete response or stable disease for at least 6 months.

      Result

      Of 62 analyzed NSCLC patients treated with immunotherapy, 20 were TMB high (32%) and 42 low (68%). 57 patients were evaluated for PD-L1, and 34 (60%) were PD-L1 high and 8 patients were PD-L1 negative (14%). TMB high patients showed more durable responses than TMB low patients although the difference was non-significant [12 of 20 (60%) versus 15 of 42 (36%); p = 0.1012]. Significantly more durable responses were seen in PD-L1 high compared to PD-L1 low NSCLC patients [19 of 34 (56%) versus 5 of 23 (22%); p=0.0143]. Combined TMB and PD-L1 high patients showed significantly more durable responses compared to both TMB and PD-L1 low patients [7 of 10 (70%) versus 1 of 15 (7%) ; p = 0.0017] . A significant longer median duration of response was observed in the combined high group (6 versus 2 months; p = 0.0024) . When PD-L1 cut-off is lowered (1% or more), still a clinical meaningful higher number of responses were seen in TMB high, than TMB low patients [11 of 16 (69%) versus 12 of 33 (36%); p= 0.0654].

      Conclusion

      Patients with high TMB, as determined by TSO500, tend to show more durable responses to immunotherapy, but the difference is not statistically significant. This is probably due to limited sample size. PD-L1 appears a stronger predictor than TMB by TSO500. TMB and PD-L1 combined, is able to identify NSCLC patients likely to respond and also to select patients that will probably lack benefit from immunotherapy. Hence TMB, as assessed by TSO500 in this study, should be considered a valuable part of comprehensive genomic profiling of NSCLC.

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