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Lunch & Poster Display session

10P - Genetic, tissue and circulating PD-L1 profiling to predict the response to immuno-checkpoint inhibitors in advanced NSCLC

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Giulia Mazzaschi

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

G. Mazzaschi1, R. Minari1, V. Ferri2, L. Gnetti3, M. Bersanelli4, A. Cavazzoni5, P. Bordi6, A. Squadrilli1, S. Buti7, A. Cosenza1, L. Ferri1, E. Rapacchi1, P.G. Petronini2, G. Missale8, F. Quaini2, M. Tiseo1

Author affiliations

  • 1 Medical Oncology Unit, University Hospital of Parma, 43126 - Parma/IT
  • 2 Medicine And Surgery, University of Parma, 43126 - Parma/IT
  • 3 Pathology, Azienda Ospedaliera di Parma, 43126 - Parma/IT
  • 4 Medical Oncology, Azienda Ospedaliero-Universitaria di Parma, Parma/IT
  • 5 Experimental Oncology, University of Parma, 46126 - Parma/IT
  • 6 Medical Oncology Unit, AOU di Parma, 43126 - Parma/IT
  • 7 Medical Oncology, AOU di Parma, 43126 - Parma/IT
  • 8 Infectious Disease Unit, University Hospital of Parma, 43126 - Parma/IT
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Resources

Abstract 10P

Background

Predictive biomarkers of immune checkpoint inhibitors (ICIs) efficacy in NSCLC are still an unmet goal. PD-L1 expression at tissue level (tPD-L1) is not steadily assessable in metastatic setting and, although routinely recommended, its dynamic nature hinders an accurate estimation. Thus, the aim of our study was to determine whether embodying genetic, tissue and circulating PD-L1 status may predict ICI response in NSCLC patients. To encompass PD-L1/PD-1 axis, we investigated the incidence of PD-1 receptor on circulating T-lymphocytes.

Methods

Peripheral blood (PB) samples from 80 consecutive ICI-treated NSCLC patients were collected at baseline. Soluble PD-L1 (sPD-L1) was measured by Human/Cynomolgus Monkey PD-L1/B7-H1 Immunoassay (R&D Systems). PD-L1 polymorphisms (rs2282055, rs4143815) were determined by RT PCR using TaqMan® method. FACS analysis was performed to detect PD-1 expression on T cells. Available tissue sections were immunohistochemically stained for tPD-L1 scoring. All these parameters were correlated with patient characteristics, survival outcome and response to treatment.

Results

sPD-L1 values ranged from 14.8 to 189.8 pg/ml (median 62.8 pg/ml). High sPD-L1 and low number of PB CD8+PD-1+ lymphocytes were detected in NSCLC cases displaying ECOG PS = 2, >3 metastatic sites, liver and pleural involvement (p < 0.05). PD-L1 polymorphisms or tPD-L1 did not appear to affect sPD-L1 levels neither correlated with clinicopathological features. Kaplan Meier curves displayed significantly reduced PFS and OS (P < 0.01) in cases with high sPD-L1, while no difference emerged according to tPD-L1 levels. PD-L1 rs4143815 allelic variant conditioned a trend of improved PFS, although without reaching statistical significance. Moreover, cases with high PB CD8+PD1+ T cells showed 12 and 22 months gain in PFS and OS (P < 0.001 vs low), respectively. Finally, a remarkable impact of sPD-L1 and CD8+PD1+ cells on Disease Control Rate was apparent (P < 0.01).

Conclusion

Our preliminary results support sPD-L1 as a promising biomarker of ICI benefit. The simultaneous assessment of the pool size of PB PD1+ effector cells might implement the strategy to predict NSCLC survival and response to treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Hospital of Parma.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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