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Daniel Adams
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MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.01 - Analysis of PD-L1 Expression on Circulating Stromal and Tumor Cells in Lung Cancer Patients Treated with Chemoradiation Therapy and Atezolizumab (Now Available) (ID 2965)
15:15 - 16:45 | Author(s): Daniel Adams
- Abstract
- Presentation
Background
We have previously shown dynamic changes to PD-L1 expression during chemoradiotherapy (CRT) could be tracked by evaluating PD-L1 expression on circulating cells. How these changes relate to immunotherapy response is unknown. We prospectively monitored PD-L1 expression in 2 cell types found in circulation (Circulating tumor cells [CTCs] and Cancer Associated Macrophage-like Cells [CAMLs]) in locally advanced non-small cell lung cancer (LA-NSCLC) patients (pts) treated with atezolizumab and CRT.
Method
Samples were taken from a completed phase II DETERRED trial (NCT02525757) where atezolizumab was added for one year after completing CRT (N=10) or concurrently and after CRT (N=30). Samples from 39 pts from the study were available for analysis. Baseline blood sample (7.5 ml) were drawn prior to start of CRT (T0), and a second sample was drawn ~1 month after completing CRT (T1), and a 3rd sample was drawn ~2 months after completing CRT (T2). Blood was processed by CellSieve™ microfilters; stained for cytokeratin/PDL1/CD45 to identify CTCs and CAMLs. PD-L1 intensity was measured and grouped by 4 scores: 0-negative, 1-low, 2-medium, & 3-high. Tumor IHC for PD-L1 levels from core biopsies was done with Dako 22c3 and was compared to T0 samples. PD-L1 levels from tumor and in circulating cells were used to evaluate PFS and OS. Significance was assessed by log-rank testing.
Result
PD-L1 IHC was available for 85% of pts, and there was at least one cytokeratin positive cell (CTC or CAML) found in 100% of T0 samples. CTCs were found in 33% of T0, 24% of T1 & 43% T2. CAMLs were found in 92% of T0, 97% of T1, & 97% of T2 samples. No correlation was seen comparing tumor PD-L1 expression percentage and the T0 PD-L1 staining intensity on CTCs/CAMLs. Tumor PD-L1>1% was found in 58% and >50% in 24% of IHC samples, yet there was no correlation between tumor PD-L1 expression and PFS or OS. At T0, PD-L1 expression in CTCs/CAMLs was low (0-1) in 18 pts and high (2-3) in 15, but no relationship to PFS (HR=0.6, 95%CI 0.2-1.7, p=0.48) or OS (HR=1.7, 95%CI 0.5-6.4, p=0.66) was found. However, pts with high PD-L1 at T1 or T2, regardless of levels at T0, had a trend towards improved PFS (HR 2.5, 95%CI 0.7-8.6, p=0.13), and a significantly better OS (HR 14.2, 95%CI 2.4-81.8, p=0.003). Interestingly, of the 15 pts who had low PD-L1 at T0, 7 had induced PD-L1 expression at T1 or T2. All samples with induced PD-L1 expression had better PFS (HR 8.3, 95%CI 1.4-50.2, p=0.02) and OS (HR 8.7, 95%CI 1.2-64.0, p=0.03) compared to those who remained low.
Conclusion
While baseline tumor or circulating cellular PD-L1 expression was not correlated with clinical outcomes, sequential monitoring of high PD-L1 expression in CTCs/CAMLs after CRT appeared to be associated with better clinical outcomes in pts who received consolidation atezolizumab after CRT, particularly in pts who had induced expression at follow up during the consolidation phase. Dynamic tracking of PD-L1 may serve as a predictive biomarker for immunotherapy effectiveness in LA-NSCLC after CRT.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-93 - Detection of Giant Cancer-Associated Macrophage-Like Cells After Concurrent Chemoimmunoradiation Is Associated with Poor Survival in NSCLC (ID 2350)
10:15 - 18:15 | Author(s): Daniel Adams
- Abstract
Background
Circulating cancer-associated macrophage-like cells (CAMLs) are a recently described stromal cell found in the peripheral blood of cancer patients that have been shown to be associated with disease progression. The presence of giant CAMLs (≥50 µm) was previously reported to be predictive of disease progression in multiple tumor types. In this phase II DETERRED trial of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) treated with atezolizumab (atezo) combined with concurrent chemoradiation, we explored the utility of CAMLs in predicting progression based on blood samples collected throughout treatment and follow up.
Method
Patients were enrolled between February 2016 and April 2018. Patients were treated with carboplatin/paclitaxel (CP) and conventionally fractionated radiation therapy (60 – 66 Gy) with atezo, followed by CP-atezo, followed by maintenance atezo. Median follow up after the completion of concurrent chemoimmunoradiation (cCIRT) was 13.5 months. CAMLs were collected by obtaining peripheral blood from patients at baseline at the beginning, during, at the end, at first follow up, and final follow up after cCIRT. Blood was filtered using CellSieveTM filtration and CAMLs quantified. CAML size ≤49 µm or ≥50 µm was quantified with the observer blinded to clinical information. Relapse free survival (RFS), distant metastasis free survival (DMFS), progression free survival (PFS), and overall survival (OS) were analyzed at each time point.
Result
We evaluated 40 patients with unresectable locally advanced NSCLC and obtained a total of 375 samples. CAMLs were identified in 80.5% of samples, averaging 2.5 CAMLs per 7.5 mL sample. Patients with giant CAMLs (≥50 µm) compared to those with smaller CAMLs (≤49 µm) exhibited no difference in RFS, PFS, DMFS, or OS at baseline, during, or immediately after completion of cCIRT. Patients with detectable giant CAMLs at the first follow up (median time 29 days from completion of cCIRT) demonstrated significantly worse RFS (HR=11.79, 95% CI 4.27-32.56, p=0.0021), DMFS (HR=6.48, 95% CI 2.15-19.54, p=0.0009), and PFS (HR=12.47, 95% CI 4.66-33.37, p=0.0014) while OS trended towards statistical significance (HR=5.39 95% CI 1.33-21.81, p=0.071). Long term evaluation of patients with CAML ≥50 µm at first follow up (N=16) revealed 3 patients who converted to CAML<49 µm at last follow up. Patients who converted did not experience any relapses, while all 13 patients who continued to have CAML ≥50 µm experienced progression or death.
Conclusion
Giant CAMLs at first follow up after completion of concurrent chemoimmunoradiation is predictive of disease progression and death. This may represent an immediate surrogate marker for poor response at the completion of definitive therapy. Long term follow up with maintenance immunotherapy indicates that a subset of patients convert from giant CAMLs to smaller CAMLs, with better outcomes than those that do not, suggesting that these patients may have derived benefit from maintenance immunotherapy. Continued prospective validation of CAMLs as a peripheral blood-based biomarker is needed to validate these findings.
