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Frank Aboubakar
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MA25 - Precision Medicine in Advanced NSCLC (ID 352)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Sebastian Defranchi, Karen Kelly
- Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)
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MA25.03 - Tumor-Infiltrating Lymphocytes (TIL) and Outcomes with Immunotherapy (ICI) or Chemotherapy in Advanced NSCLC (aNSCLC) Patients (Now Available) (ID 1374)
14:30 - 16:00 | Author(s): Frank Aboubakar
- Abstract
- Presentation
Background
Tumor infiltrating lymphocytes (TIL) morphologically assessed is prognostic in early stages in several tumors. We previously reported the correlation of TIL with immune checkpoint inhibitors (ICI) outcomes in 98 advanced (a) NSCLC patients treated with ICI. We aimed to assess the role of TIL in a larger cohort treated with ICI, and in patients exclusively treated with chemotherapy (CT).
Method
aNSCLC patients with treated with single-agent ICI, with H&E stained sample available, were included between 11/2012 and 02/2017 in 3 cancer centers (immuno-cohort). Patient’s characteristics, biological data were retrospectively collected. The CT-cohort was extracted from the prospective MSN study (NCT02105168), between 06/2009 and 10/2016, enrolling aNSCLC patients treated with platinum-based CT, and tissue available. TIL in the stroma was evaluated in archival samples. High-TIL was defined as ≥10% density. Multivariate Cox model was used to study its prognostic values on overall and progression-free survival (OS, PFS).
Result
A total of 221 patients were included in the immuno-cohort: 142 (64%) male, with median (m) age of 63, 182 (84%) smokers, 161 (77%) PS≤1, 162 (63%) adenocarcinoma; 125 (57%) received ICI as second-line. High-TIL was observed in 49/221 (28%), non-assessable in 46. High-TIL had independent impact on OS and PFS (HR 0.40; 95% CI 0.25-0.63, P<0.0001). The mPFS and OS were 3.1months (mo.) (2.5-4.9) and 11mo. (7.0-13.2) respectively. The high-TIL group had mPFS of 13mo. (5.0-NR) vs. 2.2mo. (1.7-3.0) in low-TIL group (P<0.0001). High-TIL group had mOS not reached (NR) (12.2-NR) vs. 8.4 mo. (5.0-11.6) in low-TIL (P=0.007). The CT-cohort (N=189) had high-TIL in 103/189 (54%). The mPFS and mOS were 5.7mo. (4.9-6.7) and 11.7mo. (9.3-13.0) respectively, with no association with TIL.
OS, Immuno-cohort (n=221) OS, Chemo-cohort (n=188) Hazard ratio (HR)
95% confidence interval (CI)P-value HR
95% CIP-value TIL
≥10% (high)0.46 (0.28-0.81) 0.006 1.03 (0.76-1.41) 0.84 Age
≥65 y0.86 (0.50-1.46) 0.57 0.99 (0.72-1.38) 0.99 Line of treatment*
≥ second line0.69 (0.44-1.09) 0.11 0.84 (0.60-1.16) 0.29 N# metastatic sites
>21.40 (0.88-2.20) 0.16 1.50 (1.07-2.12) 0.02 Performance status
≥22.75 (1.73-4.37) <0.0001 1.94 (1.23-3.04) 0.004 Histology
Squamous1.13 (0.70-1.81) 0.62 1.09 (0.65-1.83) 0.75 *Line of treatment: lines of immunotherapy for the Immuno-cohort; lines of chemotherapy for the Chemo-cohort.
Conclusion
High-TIL (≥10%) is a simple and accessible marker associated with better ICI outcomes, but not with CT. This suggests a potential predictive value that must be validated in larger prospectively studies.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-31 - Immunosenescence Correlates with Poor Outcome from PD-(L)1 Blockade but Not Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 2268)
09:45 - 18:00 | Author(s): Frank Aboubakar
- Abstract
Background
CD28, CD57 and KLRG1 on circulating T-lymphocytes have been identified as markers of immunosenescence. The characterization of a senescent immune phenotype (SIP) in advanced NSCLC (aNSCLC) and its impact on anti-PD(L)-1 (IO) or platinum-based chemotherapy (PCT) treatments are unknown.
Method
The percentage of circulating CD8+CD28-CD57+KLRG1+ T-lymphocytes (SIP) was assessed by flow cytometry on fresh blood from aNSCLC patients treated with IO or PCT. A SIP cut-off was identified by log-rank maximation method. Correlations with categorical or continuous variables were performed by logistic regression or t-test. Survival curves were estimated with Kaplan Meier and compared with log-rank.
Result
In the IO cohort, 43 patients were evaluated for SIP: 32% ≥ 65 years, 92% non-squamous, 51% with tumoral PD-L1 expression ≥1%, 93% chemotherapy pretreated. Disease control rate (DCR), median PFS and OS and FU were 57%, 4.6 (95% CI 0.5; 8.8) months, 13 (95% CI 2.8-23.2) months, and 14 (95% CI 8.8-19.8) months, respectively.
SIP median value was 15.4% (min 1.6%, max 57.7%). 32% of patients had >21.72% CD28-CD57+KLRG1+CD8+ lymphocytes (SIP+). SIP was not significantly associated with clinical characteristics. SIP changed according to IO response by T-sne algorithm (Figure 1A). Compared to SIP-, SIP+ patients had significantly lower DCR (81% vs 28%, p=0.002), PFS [7.3 (95% CI 4.1; 10.4) vs 1.7 (95% CI 1.2; 2.3), p=0.02] and OS [NR (95% CI 6.04; NR) vs 2.4 (95% CI 1.7; 3.1), p=0.01].
SIP was significantly associated with specific immune populations [higher peripheral activated (Ox40+ICOS+PD1+) T-regulatory (CD25highCD127low) cells, TEMRA (CCR7-CD45RA+) CD8+ and T-helper 1 (CXCR5-CXCR3+CCR4-CCR6-CCR10-) CD4+] (Figure 1B). The PCT cohort included 61 patients, 43% SIP+. No significant difference in DCR, PFS or OS were observed according to SIP.
Conclusion
Immunosenescence is observed in 32% of aNSCLC patients before IO and correlates with specific immune phenotypes. Immunosenescence predicts lower DCR, PFS and OS from IO but not from PCT.
