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Christiana Davis



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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-63 - Impact of Prior Radiation Pneumonitis on Incidence of Immunotherapy Related Pneumonitis (ID 662)

      09:45 - 18:00  |  Author(s): Christiana Davis

      • Abstract

      Background

      Patients with a history of radiation pneumonitis (RP) requiring steroids have generally been excluded from immuno-oncology (IO) trials of PD-1/PDL-1 monoclonal antibodies for safety concerns. The risk of IO-associated pneumonitis (IOP) in this group of patients (pts) is therefore unknown. We evaluated the frequency of IOP in pts who had prior RP.

      Method

      We evaluated all pts with non-small cell lung carcinoma (NSCLC) treated at our institution between 2011 and 2018 who were diagnosed with RP and at a later point received IO. Demographics, tumor characteristics, steroid use and outcomes were extracted from the electronic medical record. Median overall survival (mOS), median progression free survival (mPFS), and median time to treatment failure (mTTF) from the start of IO were estimated from Kaplan-Meier curves.

      Result

      We identified 29 pts: median age at diagnosis 63 yrs, 51.7% male, none had received prior targeted therapies. IO treatments were: atezolizumab (2), durvalumab (2), nivolumab (12), and pembrolizumab (13). Median time from RP diagnosis to start of IO was 14.2mo (2.2-75 mo). 23 pts (79%) had experienced prior grade ≥ 2 RP requiring steroids. Only 2 of the 29 pts (6.9%) developed IOP. Both pts had required steroids for prior RP and both received durvalumab; one pt was on prednisone ≥ 10mg at the start of IO. Both required steroid treatment of IOP, are still on IO and have not progressed (censored at 8.3mo and 9.9mo). OS and PFS after IO are similar (Table 1) whether or not pts required treatment for RP or were on prednisone ≥ 10 mg (or steroid equivalent) at the start of IO.

      Table 1: IO outcomes based on RP history and steroid use at start of IO

      RP Grade ≥ 2

      n=23 (95% CI)

      RP Grade < 2

      n=6 (95% CI)

      Prednisone ≥ 10mg

      n=7 (95% CI)

      Prednisone < 10mg

      n=22 (95% CI)

      All patients

      n = 29 (95% CI)

      mPFS (mo)

      5.44 (2.1-12.6)

      12.95 (0.95-)

      6.16 (2-)

      5.44 (2.1-)

      6.16 (2.4-)

      mOS (mo)

      6.6 (3.93-13.8)

      NR

      14.3 (5.3-)

      8 (3.4-16.8)

      8 (5.3-15)

      mTTFa (mo)

      2.3 (1.9-4.8)

      2.3 (1.9-)

      4.4 (2-)

      2.3 (1.9-10.9)

      2.75a (2-7)

      an=28: 1 pt lost to follow up after start of IO

      Conclusion

      In our cohort, the incidence of IOP after RP is low and similar to the rate of pneumonitis reported with pembrolizumab in pts with prior exposure to thoracic radiation.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-02 - Effect of Chemotherapy, Chemoimmunotherapy, and Immunotherapy on Parameters of T Cell Exhaustion in Metastatic Non-Small Cell Lung Cancer (ID 1880)

      10:15 - 18:15  |  Author(s): Christiana Davis

      • Abstract

      Background

      The pharmacodynamic immune response to anti-PD-1 immunotherapy can be tracked in the peripheral blood of cancer patients and is associated with response to therapy. However, it is unclear how chemotherapy and chemoimmunotherapy affect T cell activity. Given the established role of these treatments in Non-Small Cell Lung Cancer (NSCLC), we sought to compare the impact of chemotherapy, chemoimmunotherapy, and immunotherapy on T cell immunity.

      Method

      We prospectively collected blood samples in pts beginning chemotherapy, chemoimmunotherapy, or immunotherapy for metastatic NSCLC at baseline and with each cycle. Peripheral blood mononuclear cells were stained for immune markers and analyzed using 26 parameter flow cytometry. Immune response was characterized by increased expression of Ki67 on PD-1 expressing CD8 T cells. Statistical analysis was performed using paired t-test or Wilcoxon matched pairs analysis based on normality of data. All patients had CT scans with full RECIST 1.1 and tumor volume measurements.

      Result

      We analyzed 28 pts (63% female, median age = 65.5). 9 pts received chemotherapy, 12 pts immunotherapy, and 7 pts chemoimmunotherapy. Both immunotherapy (p = 0.001) and chemoimmunotherapy (p=0.016) resulted in an immune response that peaked at 3 weeks compared to baseline (Figure). No immune response was identified with chemotherapy (p=0.734). Immune response was detected in exhausted T cells (PD1+CD39+ CD8) for both immunotherapy (p =0.007) and chemoimmunotherapy (p =0.031). In addition, chemoimmunotherapy induced activation of CD27+CCR7+ memory CD8 T cells (p=0.0313), not seen with immunotherapy (p= 0.871). figure 1 wclc abstract.jpg

      Conclusion

      Chemoimmunotherapy and immunotherapy, but not chemotherapy, induced a significant immune response in the peripheral blood, peaking at 3 weeks. While immunotherapy and chemoimmunotherapy both targeted an exhausted population, chemoimmunotherapy induced an immune response in exhausted and memory T cells. We have collected more samples, and at time of the WCLC will present these data, as well as correlation with RECIST responses.