Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.

BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer. METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events. CONCLUSIONS: Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.).

Performance of T-Track® TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis.

Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track® TB, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels, and compared it to that of the QuantiFERON®-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track® TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track® TB was significantly higher (p < 0.001) than that of QFT-Plus. The overall agreement of T-Track® TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track® TB while misclassified by QFT-Plus (T-Track® TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track® TB while correctly classified by QFT-Plus (T-Track® TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track® TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.

Management of patients with SARS-CoV-2 infections with focus on patients with chronic lung diseases (as of 10 January 2022) : Updated statement of the Austrian Society of Pneumology (ASP).

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV­2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV­2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV­2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.

S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since the publication of the international IPF guideline in the year 2011 and the update 2018 several studies and technical advances have occurred, which made a new assessment of the diagnostic process mandatory. The goal of this guideline is to foster early, confident, and effective diagnosis of IPF. The guideline focusses on the typical clinical context of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardized questionnaires, serologic testing, and cellular analysis of bronchoalveolar lavage. High-resolution computed tomography remains crucial in the diagnostic workup. If it is necessary to obtain specimens for histology, transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom a bronchoscopic diagnosis did not provide the information needed. After all, IPF is a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.

Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion.

BACKGROUND: Tumour markers in pleural fluid and their diagnostic value are subject to debate. Although there are several studies on this topic, standardized cut-off values do not exist. In this study we investigated the potential of a ratio of carcinoembryonic antigen (CEA) in pleural fluid and serum, serving as an individual marker for pleural cancer manifestation. METHODS: A total of 201 consecutive patients with unclear pleural effusion were included in the study; 98 were diagnosed with malignant pleural effusion and 103 had an effusion due to other, benign reasons. CEA levels in pleural fluid and serum were measured. RESULTS: By using receiver operating characteristics analysis, at the cut-off of 1.0, the CEA ratio showed a specificity of 92% and sensitivity of 85%, with a positive predictive value of 91% and a negative predictive value of 87%. These results are higher than in previous investigations on different pleural tumour markers and their combination. CONCLUSIONS: The CEA ratio is a useful tool in predicting pleural carcinosis. Elevated results in cytology-negative patients should lead to further investigations, such as repeated cytological examination or thoracoscopy.

Fever after bronchoscopy: serum procalcitonin enables early diagnosis of post-interventional bacterial infection.

BACKGROUND: The aim of this study was to differentiate unspecific and self-limiting fever after bronchoscopy from fever due to infection by using serum procalcitonin, C-reactive protein and neutrophil count. Furthermore, frequency of fever after bronchoscopy and procedures as possible risk factors were evaluated. METHODS: Three hundred and fourteen consecutive patients were included. All bronchoscopies were performed using jet-ventilation and general anesthesia. Patients were analyzed according to interventions performed during bronchoscopy and laboratory results. Microbiological assessment was done in patients who developed fever to prove or rule out a bacterial infection. RESULTS: Forty-four patients showed fever within 24 h following bronchoscopy (14%). A bacterial infection was proven in 11 patients with fever (3.5%). Procalcitonin, neutrophil count and C-reactive protein were significantly higher in patients with fever after bronchoscopy compared to non-fever patients. To predict bacterial infection in the receiver operating analysis, procalcitonin had the highest area under the curve (0.942; 95% confidence interval [CI], 0.768 to 1.000; p = <0.001), followed by neutrophil count (AUC, 0.804; 95% CI, 0.606 to 0.946; p = 0.005), whereas CRP levels where not statistically significant. Endoscopic airway recanalization was the only intervention that induced fever more frequently than all other interventions (OR 13.629). CONCLUSIONS: Fever is frequently seen after bronchoscopy and in some cases caused by bacterial infection. Procalcitonin might be useful to distinguish a bacterial infection from unspecific self-limiting fever. Airway recanalization is a procedure that seems to induce fever significantly more often than other bronchoscopic interventions.

Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis.

BACKGROUND: Patients with chronic hypersensitivity pneumonitis (HP) can present with an insidious onset of their disease without typical fluctuating flu-like symptoms, and there are only signs of chronic respiratory failure caused by the progressive fibrotic lung disease. CASE REPORT: A 45-year-old man with a pneumomediastinum and interstitial lung disease was referred for further investigations and therapy. No traumatic event or interventional procedure had occurred prior to referral. The patient had been working in farming for almost 20 years and was exposed in childhood by his father to pigeon breeding from childhood until 20 years ago. He reported dyspnea on exercise for the previous 2 years. High-resolution CT of the lung showed a pneumomediastinum and a fibrotic interstitial lung disease without dominating ground-glass opacities. Specific IgG antibodies were markedly elevated against molds and avian antigens. Bronchoalveolar lavage demonstrated a slightly lymphocytic and neutrophilic alveolitis. After recovering from the pneumomediastinum, an open lung biopsy was performed and a UIP-pattern was detected. An inhalative challenge with hay from the work-place was positive. A diagnosis of chronic farmer's lung was made. CONCLUSIONS: Pneumomediastinum has been described in other fibrotic lung diseases, but until now it has not been described as a primary manifestation of chronic fibrotic HP. Particularly in cases of concurrent antigen sources, an inhalative challenge could be done, even in a chronic course of HP.

Acute effects of NPPV in interstitial lung disease with chronic hypercapnic respiratory failure.

OBJECTIVE: A case series evaluating the acute effects of noninvasive positive pressure ventilation (NPPV) in patients with chronic hypercapnic respiratory failure (HRF) secondary to interstitial lung diseases (ILD). PATIENTS AND METHODS: Ten patients with ILD were retrospectively evaluated. All had restrictive lung function (mean TLC, 47.6+/-12.6% predicted) and chronic hypercapnic respiratory failure (mean pH=7.39+/-0.02). Arterial blood gas analysis and lung function were compared before and after the application of controlled pressure-limited NPPV. RESULTS: Daytime PaCO(2) during spontaneous breathing decreased by 5.4+/-1.3mmHg (95% confidence interval, 4.5-6.3), from 57.7+/-5.1mmHg to 52.3+/-5.9 (p<0.001); while daytime PaO(2) increased by 3.4+/-3.3mmHg (95% confidence interval, 1.0-5.8), from 63.7+/-3.5mmHg to 67.1+/-3.4 (p=0.01); and TLC increased by 3.9+/-4.5% (95% confidence interval, 0.7-7.1), from 47.6+/-12.6%mmHg to 51.5+/-10.0% (p=0.023). CONCLUSIONS: In patients with ILD and chronic HRF controlled NPPV is tolerated and can acutely improve blood gas levels. Further studies examining the long-term benefits need to be explored.