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.).

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.

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.