Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study.

PURPOSE: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P = .005), respectively. CONCLUSION: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer.

BACKGROUND: There is a paucity of data regarding the prognostic influence of peripheral blood CD4+ T lymphopenia in non-small cell lung cancer (NSCLC). Therefore, we investigated the prognostic value of T lymphopenia in NSCLC. MATERIALS: Treatment-naive patients with a pathological diagnosis of NSCLC, at clinical stage I to IV were included in the prospective TELOCAP1 study. Lymphocytes count was evaluated in peripheral blood by flow cytometry. CD4+ and CD8+ T lymphopenia were defined as an absolute count of < 500/µL and < 224/µL respectively. The prognostic value of T lymphopenia was analyzed in the whole population, in local/loco-regional (stage I-IIIB) and in advanced (stage IV) NSCLC disease, using the Kaplan-Meier method and Cox regression models for survival curves and multivariate analysis, respectively. RESULTS: Between July 2010 and January 2014, 169 evaluable patients with clinical stage I to IV NSCLC were prospectively enrolled. The prevalence of CD4+ and CD8+ T lymphopenia was similar in the study population (around 29%). Patients with CD4+ T lymphopenia showed lower overall survival than those with CD4+ T lymphocytes count > 500/µL (median overall survival (OS) 16.1 versus 21.7 months, hazard ratio (HR): 1.616 [95% CI: 1.1-2.36], p = 0.012). This association with OS was especially marked in local/loco-regional NSCLC stages (median OS, 21.8 versus 72 months, respectively, HR: 1.88 [95% CI: 0.9-3.8], p = 0.035). Multivariate analysis confirmed the worse prognosis associated with CD4+ T lymphopenia in local/loco-regional NSCLC, but not in metastatic patients (HR 2.028 [95% CI = 1.065-3.817] p = 0.02). Restricted cubic spline analysis showed that patients with CD4+ T lymphocytes count ≤500/µL displayed a high risk of death regardless of NSCLC clinical stage. There was no obvious relationship between CD8+ T lymphopenia and clinical outcome. CONCLUSION: We identified CD4+ T lymphopenia as an independent prognostic factor in local/loco-regional stages of NSCLC and CD4+ T lymphopenia is also associated with a high risk of death, regardless of NSCLC clinical stage. TRIAL REGISTRATION: EUDRACT: 2009-A00642-55.

Let us not underestimate the long-term risk of SPLC after surgical resection of NSCLC.

OBJECTIVES: Several studies have reported that patients operated on for non-small cell lung cancer (NSCLC) are at high risk of second primary lung cancer (SPLC). However, widely varying estimates of this risk have been reported, with very few studies taking into account that these patients are at particularly high competing risk of death, due to recurrence of the initial disease and to comorbidities. Risk factor evaluation over time has significant repercussions on the post-surgery surveillance strategy offered for NSCLC. This study primarily sought to measure the risk of SPLC in a long-term follow-up series, using statistical methods considering competing risks of death. MATERIALS AND METHODS: The cumulative SPLC risk was estimated using the cumulative incidence of patients with completely resected Stage I-III NSCLC diagnosed between 2002 and 2015 based on the Doubs and Belfort cancer registry (France). A proportional sub-distribution hazard model (sdRH) was used to investigate factors associated with SPLC risk in the presence of competing risks. RESULTS: Among the 522 patients, adenocarcinoma and Stage I or II disease accounted for 52.3% and 75.7% of patients, respectively. Overall, 84 patients developed SPLC (16.1%). The cumulative risk of SPLC was 20.2% at 10 years post-surgery (95% confidence interval [CI]: 15.3-23.2), and 25.2% (CI: 19.4-31.3) at 14 years post-surgery. On multivariate analysis, the SPLC risk was significantly higher in patients with postoperative thoracic radiotherapy (sdRH 2.79; 95% CI: 1.41-5.52; p = 0.003). CONCLUSION: This study using appropriate statistical methods to consider competing risks showed that after complete NSCLC resection, the cumulative incidence function of SPLC was high, with patients receiving postoperative thoracic radiotherapy at higher risk. These data support the need for life-long follow-up of patients who undergo NSCLC surgery, with the objective of screening for SPLC.

Exophiala dermatitidis Revealing Cystic Fibrosis in Adult Patients with Chronic Pulmonary Disease.

Cystic fibrosis (CF) is a genetic inherited disease due to mutations in the gene cystic fibrosis transmembrane conductance regulator (CFTR). Because of the huge diversity of CFTR mutations, the CF phenotypes are highly heterogeneous, varying from typical to mild form of CF, also called atypical CF. These atypical features are more frequently diagnosed at adolescence or adulthood, and among clinical signs and symptoms leading to suspect a mild form of CF, colonization or infection of the respiratory tract due to well-known CF pathogens should be a warning signal. Exophiala dermatitidis is a melanized dimorphic fungus commonly detected in respiratory specimens from CF patients, but only very rarely from respiratory specimens from non-CF patients. We described here two cases of chronic colonization of the airways by E. dermatitidis, with recurrent pneumonia and hemoptysis in one patient, which led clinicians to diagnose mild forms of CF in these elderly patients who were 68- and 87-year-old. These cases of late CF diagnosis suggest that airway colonization or respiratory infections due to E. dermatitidis in patients with bronchiectasis should led to search for a mild form of CF, regardless of the age and associated symptoms. On a broader level, in patients with chronic respiratory disease and recurrent pulmonary infections, an allergic bronchopulmonary mycosis or an airway colonization by CF-related fungi like E. dermatitidis or some Aspergillus, Scedosporium or Rasamsonia species, should be considered as potential markers of atypical CF and should led clinicians to conduct investigations for CF diagnosis.