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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