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Mirte Muller

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    MA19 - Genomic Markers of IO Response (ID 922)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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      MA19.08 - Detection of Primary Immunotherapy Resistance to PD-1 Checkpoint Inhibitors (PD1CI) in 2nd Line NSCLC (ID 13916)

      16:05 - 16:10  |  Author(s): Mirte Muller

      • Abstract
      • Presentation
      • Slides


      PD1CI are capable of restoring immunity, but some patients do not benefit. While molecular tests like PD-L1 expression and TMB help in enriching response in respective subsets, a test identifying patients showing primary resistance to PD1CI which does not require tissue samples could help in optimizing treatment regimens.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Sophisticated mass spectrometry profiling data from a development set (S) of pre-treatment serum from 116 2nd line NSCLC patients treated with nivolumab were correlated with outcome data (PFS/OS)using multivariate machine learning techniques related to deep learning. The resulting test stratified patients into three groups: group A having very poor outcomes, group B having intermediate outcomes, and group C having very good outcomes. Development results were obtained using out-of-bag estimators. Two additional patient cohorts treated with nivolumab, V1(N=58) and V2(N=75), were used for validation.

      4c3880bb027f159e801041b1021e88e8 Result

      The proportions of patients in A, B, and C were 41:43:32 in S, 23:18:17 in V1, and 32:19:24 in V2. Median PFS/OS in the poor prognosis group A was 43/132 days in S, 105/189 days in V1, 90/278 days in V2, and in the good prognosis group C 276/528 days in S, 192/459 days in V1, and 155/not reached days in V2. In a comparison with historical controls treated with single agent chemotherapy and analyzed with the same technique, nivolumab appeared substantially superior in the good prognosis group C, while there was no evidence of superiority in the poor prognosis group A. In multivariate analysis including performance status, smoking history, and histology, the test remained an independent predictor of outcome. The patterns of protein expression related to poor prognosis in group A patients were associated with elevated complement, wound healing, and acute phase reactants.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We developed and validated a test stratifying patients into three groups with significantly different outcomes on nivolumab. The poor prognosis group showed little benefit from nivolumab, and other treatments may be needed, while in the good prognosis group outcomes were very good for a 2nd line population. Our results emphasize the important role of the host immune response in the prediction of PD1CI efficacy. Data on PD-L1 IHC from these cohorts will be included in the multivariate analysis and presented at the meeting.


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