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Gabriela Fernandes
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-04 - Pembrolizumab-Induced Fatal Encephalopathy (Now Available) (ID 2274)
08:00 - 18:00 | Author(s): Gabriela Fernandes
- Abstract
Background
Pembrolizumab is a monoclonal antibody against programmed cell death 1 (PD-1) receptor approved for PD-L1 positive metastatic non-small cell lung cancer (NSCLC). Neurologic adverse events associated with anti-PD-1 antibodies are rare but might be fatal.
Method
We report a case of fatal encephalopathy in a patient with metastatic NSCLC treated with pembrolizumab.
Result
A 65-year-old former smoker woman with advanced lung adenocarcinoma with a KRASmutation and an intermediate expression of PD-L1 (20-30%) previously treated with combination of carboplatin and pemetrexed started pembrolizumab (200 mg, every three weeks) after disease progression. After the second infusion of pembrolizumab, she presented with seizures and decreased level of consciousness. Concerning neurological examination, the patient was vigil, carried out only simple commands with absence of speech. Additionally, her muscular tonus was increased. Blood tests were unremarkable. Electroencephalogram was consistent with diffuse encephalopathy and also showed frequent epileptiform activity. Cerebral computed tomography and magnetic resonance revealed central nervous system (CNS) multifocal demyelination. Cerebrospinal fluid was acellular with glucose and protein within normal range. Also, microbiologic examination and polymerase chain reaction (PCR) assay for cytomegalovirus, herpes simplex 1 and 2 and John Cunningham (JC) virus were negative. Anti-onconeural antibodies were absent. Systemic corticosteroid therapy (dexamethasone 4 mg, every six hours) was initiated, with no improvement. Best supportive care was decided by a multidisciplinary team and patient died one month after admission.
Conclusion
After excluding other causes for encephalopathy as paraneoplastic syndrome, CNS infection and metastasis, temporal association with pembrolizumab administration made us suspect of an adverse event of this drug. A case of pembrolizumab-induced encephalopathy was reported in advanced NSCLC, after two doses administration and the patient recovered after high dose corticosteroids. However, another case of nivolumab-induced encephalopathy in advanced renal cell carcinoma was fatal, even with drug discontinuation and high dose corticosteroid therapy. Although anti-PD-1 rarely cause encephalopathy, our case highlights not only its occurrence but also shows that it may be rapidly progressive and irreversible. As this entity probably represents an autoimmune process due to PD-1 block, its course is impossible to predict.
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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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P1.04-59 - Modified Glasgow Prognostic Score Predict Survival Among Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (Now Available) (ID 1424)
09:45 - 18:00 | Author(s): Gabriela Fernandes
- Abstract
Background
Immune checkpoint (ICP) inhibitors improved survival among patients (pts) with metastatic non-small cell lung cancer (mNSCLC). Modified Glasgow Prognostic Score (mGPS) is an inflammation-based score with prognostic value in lung cancer. We investigated predictive value of pre-treatment mGPS among mNSCLC pts treated with ICP inhibitors.
Method
Data of mNSCLC pts treated with ICP inhibitors at Hospital São João, Porto, Portugal, were retrospectively collected. Pre-treatment mGPS was calculated using pre-treatment albumin and C-reactive protein. Survival was estimated with Kaplan-Meier method and curves were compared by log-rank test. Multivariate analysis was performed using Cox proportional hazard model.
Result
77pts were included, 71.4% were male and mean age was 66.2±9.7 years old. Most of pts had previous smoking history (77.9%) and an ECOG 0 or 1 (83.1%). Concerning tumour features, 69.5% were adenocarcinoma and 28.6% squamous cell carcinoma with a mean of PD-L1 expression of 47.6±34.3%. 10.4% had a driver mutation. Nivolumab was used in 71.4% and pembrolizumab in 28.6%. Partial response was achieved in 27.3%, stable disease in 31.2% and 39.0% had disease progression. Overall, progression-free survival (PFS) and overall survival (OS) were 5.0 (95% CI, 2.0-7.9) and 15.0 (95% CI, 8.4-21.6) months (mo), respectively. Adverse effects (AE) occurred in 26.0%. A lower mGPS was associated with superior OS (0: not reached; 1: 7.0 mo; 2: 3.0 mo, p=0.002) and PFS (0: not reached; 1: 4.0 mo; 2: 2.0 mo, p<0.001). In addition, ECOG 0-1was associated with superior OS (16.0 vs 3.0mo, p=0.011) and PFS (6.0 vs 2.0mo, p=0.023), comparing to ECOG 2-3. Better survival was also verified in pts with AE occurrence (OS: p=0.001 and PFS: p<0.001) and in pts with lower number of metastatic sites (OS: p=0.004 and PFS: p<0.001). In a multivariate model, adjusting for ECOG, number of metastatic sites and AE occurrence, lower mGPS was associated to a better survival, regarding OS (p=0.004) and PFS (p=0.002).
Conclusion
Pre-treatment mGPS influenced OS and PFS and may represent a useful tool to predict survival in pts with mNSCLC treated with ICP inhibitors.
