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Yuhei Harutani
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P60 - Tumor Biology and Systems Biology - Basic and Translational Science - Immune Bio (ID 198)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P60.08 - Impact of CD24 and CD47 Tumor Expression on Efficacy and Serum Cytokine Alteration with PD-1/L1 Inhibitors in Non-Small Cell Lung cancer. (ID 3235)
00:00 - 00:00 | Author(s): Yuhei Harutani
- Abstract
Introduction
To prime tumor-specific lymphocytes, it is crucial that antigen-presenting cells phagocytose tumor cells and process the antigen to load peptides into major histocompatibility complex class I or II molecules. Although enhanced efficacy of the combination of PD-1 inhibitors with inhibitors of CD47, a potent phagocytosis inhibitor, underline the importance of such a mechanism that begins with the phagocytosis, the association of phagocytosis-inhibiting molecules on tumor with efficacy of or immune-reaction with immune-checkpoint inhibitors (ICI) remain unexplored. CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, has recently been reported to be a potent inhibitor of phagocytosis, independent of CD47, by binding to sialic acid-bounding Ig-like lectin 10 on macrophages.
Methods
This is a post hoc analysis of prospective biomarker study, which enrolled 106 patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICI monotherapy between December 2015 and September 2018, and we investigated in 68 patients with preserved evaluable tissue samples taken before start of ICI treatment. CD24, CD47, and PD-L1 expression in tumors were stained by immunohistochemistry and judged to be positive if membranous staining was present and evaluated by tumor proportion score (TPS). Using peripheral blood which was collected by the observational study, 57 serum proteins at the time of ICI initiation and in weeks 4 – 6 later were quantified.
Results
The median CD47 TPS was 60% (0 – 100). Regarding CD24, more than half of enrollments expressed only <1% and cases of CD24 TPS ≥1 were 27. There were no differences in CD24 TPS or CD47 TPS between PD-L1 high (TPS ≥50) and low groups (p=0.551, 0.097). Cases were divided into two groups according to CD47 TPS by median, 60, and CD24 TPS by 1, respectively, and compared. CD24 positivity (TPS ≥1) was negatively associated with progression free survival of ICI when PD-L1 TPS <50 (median progression free survival (PFS); 37 vs. 127 days, p=0.033), but no association was observed when PD-L1 TPS ≥50 (median PFS; 494 vs. 144 days, p=0.168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4 – 6 weeks later, and such increase was notably observed only when PD-L1 TPS <50 (p=0.0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs. 233 days, p=0.028). CD47 TPS high (≥ 60) significantly suppressed the increase in VEGF-A, D and PDGF-AB/BB after ICI initiation, but there was no association between CD47 tumor expression and the efficacy of ICI.
Conclusion
CD24, not CD47, is a potential negative predictive marker of ICI in advanced, non-small cell lung cancer with PD-L1 TPS <50. Tumor expression of CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis such as CCL2, VEGF, and PDGF) after ICI initiation.
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P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P75.15 - Predictive Factors of Survival in Non-Small Cell Lung Cancer Patients Without Durable Response to PD-1/L1 Inhibitors (ID 3213)
00:00 - 00:00 | Presenting Author(s): Yuhei Harutani
- Abstract
Introduction
Although durable responses by immune checkpoint inhibitors (ICIs) such as PD-1/L1 inhibitors have been taken noticed in patients with advanced non-small cell lung cancer (NSCLC), trials indicate a part of patients without durable responses also survive for a long time. ICIs improve survival rather than progression free survival (PFS) and may also contribute to prolonged survival in non-durable responders (NDRs), however, factors associated with survival in NDRs remain unknown.
Methods
Between December 2015 and September 2018, 106 patients with advanced NSCLC treated with ICI monotherapy were enrolled in a prospective-observational study, which routinely collected peripheral blood samples including at the time of ICI initiation and progressive disease (PD). Fifty-seven serum proteins were quantified with Luminex® 200 analyzer. Sixty-nine patients, who progressed or died within 6 months after ICI initiation were defined as NDRs, and we explored clinical factors and serum proteins associated with survival in NDRs at the time of ICI initiation and PD. Continuous variables except for age were divided to two groups by median for statistical analysis.
Results
Age [median(range)]: 70 (31 – 91), sex: male/female 50/19, PS: 0-1/2-4 49/20, agents: Nivolumab/Pembrolizumab/Atezolizumab 34/27/8, PD-L1: <1%/1-49%/≧50%/NE 8/11/20/30, gene alteration: EGFR/ALK/ROS1/wt or unknown 10/3/1/55, treatment line: 1/2/≧3 14/31/24. Median PFS was 44 days (95% confidence interval (CI): 39 – 56). Median overall survival time (OS) and survival time after PD were 211 (95%CI: 158 – 425) and 173 days (95%CI: 114 – 340), respectively. By multivariate Cox proportional regression hazard model for OS adjusted with age, PD-L1 (≧50% or not), performance status (PS) (0 – 1 or not) and sex, neutrophil lymphocyte ratio (NLR) (> 3.75) [HR 3.96 (95%CI: 1.33 – 11.84), p=0.01], CRP (>1.44 mg/dl) [HR 6.07 (95%CI: 1.95 – 18.88), p=0.002], and follistatin (>683 pg/ml) [HR 4.58 (95%CI: 1.16 – 18.05), p=0.03] were significant predictive factors at the baseline. All of NLR, CRP, and follistatin were also associated with survival time after PD (HR 3.23; p=0.03, HR 5.17; p=0.004, HR 4.14; p=0.045, respectively), although NLR and follistatin were not associated with PFS (p=0.20, 0.32, respectively). We also explored predictive factors at the time of PD for survival time after progression. In 47 patients with serum protein measurement at the time of PD, any factors were not statistically associated with survival time after progression by the multivariate analysis.
Conclusion
In NDRs, NLR, CRP, and serum follistatin at the time when ICI starts, not when PD, are predictive for survival. NDRs with low level of these factors may be better treated actively after ICI cessation.
