Virtual Library

Start Your Search

Melina E Marmarelis



Author of

  • +

    MA05 - Update on Clinical Trials and Treatments (ID 123)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • +

      MA05.10 - Pembrolizumab in the Treatment of Patients with Malignant Pleural Mesothelioma Following Progression After Initial Chemotherapy (Now Available) (ID 2788)

      13:30 - 15:00  |  Author(s): Melina E Marmarelis

      • Abstract
      • Presentation
      • Slides

      Background

      Checkpoint inhibitor (CPI) therapies have demonstrated clinical benefit in patients (pts) with malignant pleural mesothelioma (MPM) and are now included in the NCCN guidelines as an acceptable treatment option. Herein, we report our initial experience treating pts with MPM in the palliative second line or greater setting.

      Method

      Between January 2016 and November 2018, 74 pts with biopsy proven MPM were treated with pembrolizumab every three weeks until confirmed disease progression or unacceptable toxicity. Progression-free survival (PFS) and OS were defined as the time from first pembrolizumab dose to recurrence and death, respectively, or to last contact. Response rates (RR) were measured by a dedicated thoracic radiologist using modified RECIST 1.1 criteria. Adverse events were routinely recorded/scored at each follow up visit. according to CTCAE 4.0 with level of attribution to pembrolizumab.

      Result

      Demographics of the 74 pt cohort are shown in table 1. Twently-nine (39%) of pts experienceda total of 39 grade 1-2 adverse events, possibly or definitely related to therapy (Table 2). There was one grade 4pneumonitis that resulted in new requirement for oxygen, which resolved with steroids; and one patient experienced leukoencephalopathy that resulted in death. The overall response rate (including only partial responses by modified RECIST 1.1) for the entire cohort was 26%. Median progression free survival and overall survival for the entire cohort were 2.8 months and 7.9 months, respectively.

      Table 2: Adverse Events

      CTCAE 4.0 Grade

      AE Description

      1-2

      3-4

      5

      hypothroid

      5

      arthralgias

      8

      colitis

      3

      diarrhea

      2

      lip lesion

      1

      pneumonitis

      2

      1

      SICCA syndrome

      1

      thrombocytopenia

      1

      dermatitis

      1

      hypopigmentation

      1

      nephritis

      1

      fatigue

      1

      abdominal pain

      1

      uveitis

      1

      transaminitis

      1

      elvated alk phos

      1

      leukoencephalopathy

      1

      pruritis

      3

      hypercalcemia

      3

      rash

      2

      Table 1: Demographics

      Age in Years

      median (range)

      Min

      73

      (52-92)

      Gender

      Patients (N=74)

      Female

      29

      39%

      Male

      55

      74%

      Histology

      Epithelial

      58

      78%

      Sarcomatoid

      6

      8%

      Biphasic

      10

      14%

      # of chemotherapy courses

      0

      3

      4%

      1

      42

      57%

      2

      22

      30%

      3-4

      7

      9%

      # of radiotherapy courses

      0

      42

      57%

      1

      30

      41%

      2-3

      6

      8%

      Surgical Resection

      Have EPD

      24

      32%

      Did not have EPD

      50

      68%

      PDL1

      Negative

      21

      28%

      Positive

      12

      16%

      Not Determined

      42

      57%

      Conclusion

      Pembrolizumab in the Tx of MPM was reasonably well tolerated in this large, single institution experience. RR, PFS and OS appear remarkably similar to recent published data from a registry study of off-label use of pembrolizumab in pts with MPM in Switzerland and Australia (include reference). Ongoing studies include analysis of PDL-1 and other potential immunotherapy response biomarkers.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      MA11.11 - STK11/LKB1 Genomic Alterations Are Associated with Inferior Clinical Outcomes with Chemo-Immunotherapy in Non-Squamous NSCLC (Now Available) (ID 2898)

      14:00 - 15:30  |  Author(s): Melina E Marmarelis

      • Abstract
      • Presentation
      • Slides

      Background

      Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread use of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we present updated data on the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy from a large retrospective multi-institution international study.

      Method

      620 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 21 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 468 pts treated with first-line CPP (or >1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 152 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP.

      Result

      Among 468 CPP-treated pts, STK11/LKB1 genomic alterations (N=118) were associated with significantly shorter PFS (mPFS 5.0m vs 6.8m, HR 1.45, 95% CI 1.11 to 1.91; P=0.007) and shorter OS (mOS 10.6m vs 16.7m, HR 1.46, 95% CI 1.04 to 2.07; P=0.031) compared with STK11/LKB1-wt tumors (N=350). The likelihood of disease progression as BOR to CPP differed significantly between the two groups (29.5% vs 17%, P= 0.006). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N=435) (mPFS 5.0m vs 6.9m, HR 1.48, 95% CI 1.12-1.95, P=0.006 and mOS 10.6m vs 16.7m, HR 1.45, 95% CI 1.02-2.05, P=0.036). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not result in significant improvement of PFS (mPFS 5.0m vs 3.9m, HR 0.82, 95% CI 0.63 to 1.07, P=0.14) or OS (mOS 10.6m vs 9.1m, HR 0.93, 95% CI 0.67 to 1.30, P=0.69) compared to CP alone.

      Conclusion

      In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      P1.01-63 - Impact of Prior Radiation Pneumonitis on Incidence of Immunotherapy Related Pneumonitis (ID 662)

      09:45 - 18:00  |  Author(s): Melina E Marmarelis

      • 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.

  • +

    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
    • +

      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): Melina E Marmarelis

      • 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.

  • +

    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.14-26 - Outcomes in Patients with Compound Epidermal Growth Factor Receptor (EGFR) Mutations After Treatment with Tyrosine Kinase Inhibitors (TKIs) (ID 1090)

      10:15 - 18:15  |  Author(s): Melina E Marmarelis

      • Abstract
      • Slides

      Background

      TKIs targeting EGFR have changed the therapeutic paradigm for patients (pts) with non-small cell lung cancer (NSCLC) harboring classic sensitizing mutations in EGFR (L858R and Exon 19del). Less is known about the efficacy of TKIs when a sensitizing mutation is co-existent with another, not resistance-associated EGFR mutation (compound EGFR mutations). We report the outcomes of pts with de novo compound EGFR mutations treated with TKIs.

      Method

      We identified pts with compound EGFR mutated NSCLC (plasma or tissue detection) treated at a single center. All disease-associated EGFR mutations were included with the exception of T790M and C797S. Time to treatment failure (TTF) was calculated from the start of TKI therapy until treatment discontinuation for any reason (i.e. disease progression, toxicity, pt choice or death). Overall survival (OS) was calculated from the start of TKI until death. Median OS (mOS) and TTF (mTTF) were estimated from Kaplan-Meier curves.

      Result

      24 pts with compound EGFR mutations were identified (median age 60, 67% female, 29% never smokers) between 2011 and 2018 (Table 1). Of the 16 (67%) who received a TKI, the most common mutation was G719X (n=9). Exon 19 deletions (del) were present in 2 patients (1 with G719X). L858R was found in 5 patients. Of the 8 pts who did not receive a TKI, 4 had early stage NSCLC that never progressed, 2 had local recurrence treated with surgery/radiation and 2 had metastatic recurrence. Among those treated with a TKI, the mTTF was 13.6 months (mo) and mOS was 32.7 mo. There was no difference in mTTF between erlotinib (n=10) and afatinib (n=6) (13.6 vs. 8.8 mo, log rank p=0.67). Median follow up was 33 mo. In 7 pts who had both baseline tissue and plasma testing, plasma detected all non-classic mutations.

      Conclusion

      The mOS and mTTF in this cohort of pts with compound EGFR mutations compare favorably to the historical progression free survival and mOS for pts with classic sensitizing mutations in EGFR treated with erlotinib or afatinib.

      Table 1: Compound EGFR mutations (n=24)

      Exon 3

      Exon 18

      Exon 19

      Exon 20

      R108K

      E709X

      del

      S768I

      V769M

      R776H

      Exon 18

      G719X

      5

      1

      8

      1

      1

      Exon 19

      del

      1

      Exon 21

      L858R

      3

      2

      L861Q

      1

      1

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.