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Simona Carnio
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MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:David R Spigel, Roberto Ferrara
- Coordinates: 9/08/2019, 13:30 - 15:00, Vancouver (2003)
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MA07.02 - Early Change of dNLR Is Correlated with Outcomes in Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 2676)
13:30 - 15:00 | Author(s): Simona Carnio
- Abstract
- Presentation
Background
The [neutrophils/[leucocytes-neutrophils] ratio (dNLR) correlates with immune checkpoint inhibitors (ICI) outcomes in advanced non-small cell lung cancer (aNSCLC) patients. Significance of early dNLR change after the first course of ICI is unknown.
Method
Patients with NSCLC treated with ICI (PD(L)1+/-CTLA4) between Nov. 2012 and Jun. 2018 at 16 EU/US centers were included. A control group treated with chemotherapy (CT) only was also evaluated (NCT02105168). dNLR was collected at baseline (B) and at cycle 2 (C2). Patients were categorized as low vs high dNLR at each timepoint (defined as < vs > 3, as previously done), and the change between B and C2 (good = low at both timepoints, poor = high at both timepoints, mixed = different at each timepoint).
Result
1485 patients treated with ICI were analyzed. PDL1 was negative in 162 (11%), 1-49% in 178 (12%), ≥50% in 201 (14%), and missing in 944 (64%). dNLR at B and C2 did not associate with PD-L1 status.
At baseline, dNLR was high in 509 (34%) patients and associated with worse PFS compared to those patients with low dNLR at baseline (HR 1.56, P<0.0001) and OS (HR 2.02, P<0.0001). At C2, dNLR was high in 484 (34%) and similarly associated with worse outcomes compared to patients with low dNLR at C2 (PFS HR 1.64, P<0.0001; OS HR 2.13, P<0.0001).
Between B and C2, dNLR remained low in 804 (56%, « good ») or high in 327 (23%, « poor ») or changed in 310 pts (22%, « intermediate »). Those with a good dNLR demonstrated mPFS 5.3, mOS 18.6 mo), followed by those intermediate with mixed dNLR (mPFS 3, mOS 9.2 mo), and finally poor dNLR (mPFS 2, mOS 5mo). Outcomes were independant of PD-L1 expression (adjusted HR for PFS 1.94 for intermediate and 3.16 for poor groups, compared to good dNLR group, P<.001; adjusted HR for OS was 2.08 for intermediate and 3.67 for poor groups, P<0.001).A bootstrap tested the stability of OS/PFS prediction (P<0.001).
In the chemo-cohort (n=173), high C1-dNLR (n=81, 47%) was not associated with OS (P=0.84).
Conclusion
dNLR at baseline, at cycle 2, and the change between these two timepoints associated with outcomes in patients treated with immunotherapy independent of PD-L1, but not in patients treated with chemotherapy alone. dNLR is specifically prognostic in the context of immunotherapy.
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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
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-45 - Immune-Oncology Gene Expression Profiles Allow Lung Cancer Patients’ Stratification and Identification of Responders to Immunotherapy (ID 2339)
09:45 - 18:00 | Author(s): Simona Carnio
- Abstract
Background
Immune-checkpoint inhibitors (ICI) represent a new standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Beyond tumor PD-L1 protein expression, other biological parameters are emerging as potential predictive biomarkers. We evaluated high-throughput immune-related Gene Expression Profiles (GEP) in tumor tissue from ICI-treated patients, correlating immune activation data with clinical response to immunotherapy.
Method
RNA was isolated from tumor tissues of 44 metastatic NSCLC patients treated with Nivolumab (as 2nd or 3rd line therapy) and collected from different Italian centers. The nCounter® PanCancer IO360™ Panel was applied on NanoString platform to analyze 770 genes involved in key immuno-oncology pathways. Clinical-pathological data, as well as best response to ICI treatment, have been collected.
Result
Patients were dichotomized as responders (7 Partial Response and 19 Stable Disease) and non-responders (18 Progressive Disease). A pre-identified T-cell inflamed signature was evaluated at single gene level and the expression of CCL5, CD27, CD276, CMKLR1, CXCL9, CXCR6, LAG3, NKG7, PDCD1LG2, PSMB10, TIGIT was higher in the responder group, although not reaching statistical significance. Moreover, higher STING, CGAS and IRF3 genes expression level appeared to be more commonly associated with non-responder patients.
Considering the disease stage at the time of diagnosis, a different gene panel (CCL5, CD27, CD274, CD8A, CXCL9, CXCR6, HLA-DQA1, HLA-DRB1, HLA-E, IDO1, LAG3, NKG7, PSMB10, TIGIT) resulted to be more expressed in early and locally advanced (16 from stage I to IIIA) compared to metastatic (28 stage IV) tissue samples.
Conclusion
A trend in differential expression patterns was observed between responders and non-responders NSCLC patients treated with Nivolumab and additional analyses on this cohort could reveal specific pathways able to predict unresponsiveness to ICI treatment. Different disease stage seems also to influence immune-related GEPs.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-14 - NLR, dNLR and PLR as Possible Predictive Markers in Patients with NSCLC Treated with ICI (ID 1063)
10:15 - 18:15 | Author(s): Simona Carnio
- Abstract
Background
Clinical evidence suggests a possible predictive role of Neutrophil-to-Lymphocyte ratio (NLR), derived Neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and Platelet-to-Lymphocyte ratio (PLR) in different tumors, including non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI).
Method
In this Italian multicenter retrospective trial NLR, dLNR, PRL fluctuations were analyzed in patients with stage IV NSCLC treated with ICI. Those rates were assessed at baseline, before the second, third and fifth cycles. In patients still on treatment, samples were collected also at 1 and at 2 years from ICI start. The primary objective was the relationship between baseline ratios and response to ICI, through the identification of different cut-offs estimated using ROC curves.
Result
Data of 402 patients receiving ICI (antiPD1 91%, antiPDL1 7% and antiPDL1 plus antiCTLA-4 2%) were analysed: 287 (71%) were males, median age was 65 (39-86 yrs-old), 84 patients (21%) were on first line treatment. The most common histology was adenocarcinoma (62%) and 95% of patients had an ECOG performance status of 0-1. One hundred and eleven (30%) patients were using steroids in permissive doses for ICI. Disease control rate (DCR) was observed in 228 patients (58%) with 95 (24%) reporting an immune objective response. Median progression free survival was 5,3 months and the median overall survival was 9,6 months, after a median follow-up of 9,6 months (range 4,0-13.0). Basal NLR, dNLR and PRL were predictive of response (p=0.0002, p=0.0003 and p=0.0304, respectively). Best response categories were dichotomized in Response (SD + PR + CR) versus no Response (PD). With this classification, the differences were more pronounced and statistically significant for basal NLR and dNLR (p=0,045 and p=0,004, respectively). The cut-off values for basal NLR and dNLR were defined (BLNLR=2,46; BLdNLR=1,61) to identify patients most at risk of “non Response” through the ROC curves. Confounding factors were assessed using logistic regression models (age, gender, smoking). During treatment, an increase in the values was observed at the time of progression, both for NLR (average variation: -1.57) and for dNLR (average variation + 0.32), even if the statistical significance is limited to NLR (p = 0.041).
Conclusion
NLR, dNLR and PLR are independent factors of response to ICI. Compared to the present literature data, this study highlights that NLR ratio may predict progressive disease earlier than radiological restaging.
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P2.04-15 - Association Between Opioids and Outcome of 1st Line Immunotherapy in Advanced NSCLC Patients: A Retrospective Evaluation (Now Available) (ID 2428)
10:15 - 18:15 | Author(s): Simona Carnio
- Abstract
Background
Opioids represent the pharmacological backbone of cancer-related pain treatment. However, preclinical studies suggest that opioids can cause immunosuppression. Recently, immune checkpoint inhibitors (ICIs) have become available for treatment of patients with advanced NSCLC. With this study we aimed at retrospectively evaluate the impact of chronic opioid treatment on the outcome of advanced NSCLC (aNSCLC) patients treated with first-line ICIs.
Method
We retrospectively reviewed the records of aNSCLC patients treated with anti-programmed-death-1 (PD-1) or its ligand (PD-L1) single-agent ICIs in 2 Italian institutions. We included all patients with enough follow-up to have at least one radiological evaluation during ICIs treatment. Patients with rapid clinical progression were included in the analysis. We analyzed response rate (RR), progression-free survival (PFS), and overall survival (OS). Response was evaluated using RECIST v1.1 criteria.
Result
75 patients were found, 64 included in the analysis. Mean age at diagnosis was 66.5 years (range 37-84), 65% were male. Histological type were: 76.5% adenocarcinoma, 14% squamous, 9.5% others, most with high PD-L1 expression (90.5% with ≥50% TPS). 58 patients (90.6%) were stage IV at ICIs start, with mean number of metastatic sites 1.8. Most patients were current/former smokers (87.5%); ECOG performance status (PS) at ICI start was: 0 in 34 pts (53.1%), 1 in 25 (39%), 2 in 5 (7.9%). 20 patients were receiving opioids at ICIs start (31.3%), with a mean daily dose equal to 59 mg of oral controlled-release morphine. With a median follow-up of 10.9 months, the median number of ICIs cycles was 7.5 (range 1-26). RR, mPFS and mOS in the whole series were 40.6%, 9.4 months and 17.1 months, respectively. Compared to the others, patients receiving opioids had numerically lower RR (30% vs 45.5%, p=0.24), a shorter PFS (median 12.7 vs 1.7 months, Hazard Ratio [HR] 4.16, 95%CI 2.15-8.05, p<0.001) and OS (median not reached vs 3.2 months, HR 4.68, 95%CI 2.09-10.52, p<0.001). At the multivariate analysis, opioid use continued to be significantly associated with worst PFS (HR 3.19, 95%CI 1.45-7.01, p=0.004) and OS (HR 4.16, 95%CI 1.61-10.76, p=0.003), even when accounting for PS, disease stage and number of metastatic sites.
Conclusion
Our results suggest a possible detrimental effect of opioids in aNSCLC patients treated with first line single-agent ICIs, even when correcting for other prognostic factors. However, due to the short follow-up, the small number of patients, and the lack of a control group, our results should be considered exploratory.
