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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5159 - HLA-DrbB1 heterozygosis and early auto-antibody rise predict prolonged survival in metastatic NSCLC patients undergone PD-1 blockade.

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Tumour Immunology;  Translational Research

Tumour Site

Presenters

Pierpaolo Correale

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

P. Correale1, R. Giannicola1, C. Botta2, P.S. Tagliaferri2, P. Pastina3, M. Monoriti4, R. Saladino4, A. Falzea1, V. Barbieri2, G. D'Arrigo5, G. Tripepi5, P. Tassone2, L. Pirtoli3

Author affiliations

  • 1 Onco-hematology And Radiotherapy, Grande Ospedale Metropolitano, 89125 - Reggio Calabria/IT
  • 2 Magna Grecia University, Medical Oncology Unit, AUO Mater Domini, 88100 - Catanzaro/IT
  • 3 Radiotherapy Unit, University Hospital of Siena, Istituto Toscano Tumori, 53100 - Siena/IT
  • 4 Patologia Clinica, Grande Ospedale Metropolitano, 89125 - Reggio Calabria/IT
  • 5 Cnr, CNR IFC, Reggio Calabria, 89125 - Reggio Calabria/IT
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Resources

Abstract 5159

Background

PD-1/PDL-1-blockade by nivolumab is a promising and efficacious treatment for mNSCLC patients. It acts by rescuing PD-1-inactivated tumor-infiltrating-lymphocytes, an event indispensable for a short-term antitumor response. Nevertheless, continuous immune-priming is needed to avoid clonal-T-cell exhaustion and to prolong patient survival. We have investigated, whether class-I/II HLA homo/heterozygosis, antigen cascade and cross-priming measured as auto-antibody (AAbs) rise may predict patient outcomes with nivolumab treatment.

Methods

This is a retrospective study including ninety-eight mNSCLC patients who received nivolumab (3mg/kg every 15 days) between September 2015 and March 2018 as a second line of treatment. Log-rank test and Mantel-Cox analysis were carried out to correlate PFS and OS with homo/heterozygosis HLA status, respectively, for locus A, B, C and DrB1 and baseline and post-treatment levels of AAbs [anti-nuclear antibodies (ANA), extractable nuclear antigen (ENA), anti-smooth cell antigen (ASMA), anti-neutrophil cytoplasmic antigens (ANCA)].

Results

A PFS and OS of 13.68 (95%CI:10.85 -16.5) and 16.41 (95%CI:13.48- 19.34) months, were, respectively, recorded. They were not correlated with histology, sex or previous radiotherapy. HLA-DrB1 heterozygosis showed a significant advantage in OS (HR = 0.18, 95%CI:0.036-0.902; p = 0.037). A prolonged survival was also found in patients who showed early rise (within thirty days) of one (score 1, HR = 0.235, 95% CI: 0.084-0.654. P = 0.018) or more AAbs (score 2, HR = 0.22, 95% CI: 0.081-0.624, P = 0.001). Finally, Cox analysis revealed a predictive role for treatment-related early increase in eosinophil cell counts (OS, HR: 0.68, 95% CI: 0.57-0.81, P = 0.031).

Conclusions

Heterozygosis in the HLA-DrB1 locus and early rise in ANA, ENA and/or ASMA is predictive of longer OS in nivolumab-treated mNSCLC patients. These data support the hypothesis that continuous and efficient tumor antigen-release and cross-priming during PD1/PDL-1 blockade is critical for long-term patient survival. These results offer a strong rationale to design future immunotherapy trials in NSCLC patients.

Clinical trial identification

Legal entity responsible for the study

Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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