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Wen-Rong Li
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OA01 - Precision Medicine and Personalized Therapy for Lung Cancer (ID 1)
- Event: NACLC 2019
- Type: Oral Abstract Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 10/11/2019, 14:00 - 15:40, Imperial Ballroom (B2 Level)
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OA01.02 - Prognostic Value of Baseline Autoantibodies in Metastatic NSCLC Patients Receiving PD-/PDL-1 Targeted Immunotherapy (ID 105)
14:00 - 15:40 | Author(s): Wen-Rong Li
- Abstract
Background:
Immune checkpoint inhibitors targeting either programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have advanced the paradigm for management of Non-small Cell Lung Cancer (NSCLC). However, only a subset of patients showed durable response leaving the majority at risk of progression especially with lack of feasible biomarkers for appropriate selection of candidates. Humoral immunity is involved in tumor-immune interaction by generation of neoantigens associated autoantibodies. These circulating autoantibodies might provide clinically important prognostic information on response to immunotherapy.
Method:
Pretreatment sera from metastatic stage NSCLC patients (n=81) receiving non-frontline standard PD-1/PDL-1 targeted immunotherapy as non-frontline were evaluated for autoantibodies using EMD Millipore’s MILLIPLEX® Human Cancer Autoantibody Magnetic Bead Panel. This panel includes Alpha-enolase (ENO1), Cancer/Testis Antigen 1? (CTAG1B/NY-ESO-1), Cyclin-dependent kinase 4 inhibitor A (p16-INK4a), G2/mitotic-specific cyclin-B1 (CCNB1), Galactose-specific lectin-1 (Galectin 1), Galactose-specific lectin-3 (Galectin 3), Heat shock protein 60 (HSP60), Hypoxia-inducible factor 1-alpha (HIF1?), Insulin-like growth factor 2 mRNA-binding protein 2 (IMP-2), Insulin-like growth factor 2 mRNA-binding protein 3 (IMP-3), Mucin 1 (MUC1), Receptor tyrosine-protein kinase (HER2/ErbB2), sex determining region Y (SRY)-box 2 (SOX2), Survivin (Survivin/BIRC5), Tumor protein p53 (p53). The Panel was processed according to manufacturer-defined protocols and read using a Luminex® FLEXMAP 3D®.All statistical relationships were determined using the Log-Rank test in relation to overall survival (OS) and progression-free survival (PFS). Additionally, observed adverse events were correlated to the autoantibody’s levels, excluding any autoimmune preoccupied co-morbidity, and statistically assessed using Mann-Whitney U test.
Results:
Baseline level of autoantibodies specific to IMP2 was significantly associated with time to progression (HR=2.28, 95%CI=1.21-4.3, p=0.01), whereas P53(HR=2.05, 95%CI=1-4.17, p=0.049), HIF1?(HR=3.02, 95%CI=1.05-8.65, p=0.04), HSP60(HR=0.39, 95%CI=0.16-0.85, p=0.02,), and CTAG1B/NY-ESO-1(HR=0.29, 95%CI=0.1-0.8, p=0.017) autoantibodies where significantly associated with overall survival. After considering comorbidity, patients who developed treatment associated pneumonitis (n=5) showed lower levels of ENO1, MUC1, and CTAG1B (all p<0.02) compared to the rest of the cohort. Skin adverse events (n=7) were also associated with significantly lower level of MUC1, CTAG1B, and GAL1 (all p<0.02) compared to the rest of the cohort.
Conclusion:
Baseline autoantibodies appeared to have a potential benefit in selecting candidates for PD-1/PDL-1 targeted immunotherapy in metastatic NSCLC and in this limited dataset were associated with the development of some autoimmune adverse events. Further studies are ongoing.
