The aim of this study was to investigate the expression of the coinhibitory molecule PD-L1/CD274 in monocytes and dendritic cells (DC) in the blood of lung cancer patients undergoing PD1 inhibitor therapy and to correlate data with patient’s outcome. PD-L1/CD274 expression of monocytes, CD1c⁺ myeloid DC (mDC) and CD303⁺ plasmacytoid DC (pDC) was determined by flow cytometry in peripheral blood at immunotherapy onset. The predictive value of the PD-L1/CD274-expression data was determined by patients’ survival analysis. Patients with a high PD-L1/CD274 expression of monocytes and blood DC subpopulations rarely responded to PD1 inhibitor therapy. Low PD-L1/CD274 expression of monocytes and DC correlated with prolonged progression-free survival (PFS) as well as overall survival (OS). The highest PD-L1/CD274 expression was found in CD14⁺HLA-DR⁺⁺CD16⁺ intermediate monocytes. Whereas the PD-L1/CD274 expression of monocytes and DC showed a strong positive correlation, only the PD-L1/CD274 expression of DC inversely correlated with DC amounts and lymphocyte counts in peripheral blood. Our results implicate that a high PD-L1/CD274 expression of blood monocytes and DC subtypes is a risk factor for therapy response and for the survival of lung cancer patients undergoing PD1 inhibitor therapy.

Objectives: Small-cell lung cancer (SCLC) is a lung malignancy with high relapse rates and poor survival outcomes. Treatment-resistant disease relapse occurs frequently and effective salvage therapies are urgently needed. Materials and Methods: We aimed to define efficacy and safety of checkpoint inhibitors (CPIs) in a heterogeneous population of relapsed and refractory SCLC patients in a large retrospective multicentric real-world cohort across German tertiary care centers. Results: A total of 111 patients from 11 treatment centers were included. Median age of all patients was 64 years, and 63% were male. Approximately one-third of all patients had poor performance status [Eastern Cooperative Oncology Group (ECOG) ⩾ 2], and 37% had known brain metastases. Patients were heavily pretreated with a median number of prior therapy lines of 2 (range, 1–8). Median follow-up of the entire cohort was 21.7 months. Nivolumab and Nivolumab/Ipilimumab were the most common regimens. Overall disease control rate was 27.2% in all patients and was numerically higher in CPI combination regimens compared with single-agent CPI (31.8% versus 23.8%; p = 0.16). Median overall survival (OS) was 5.8 months [95% confidence interval (CI), 1.7–9.9 months]. The 12- and 24-month survival rates were 31.8% and 12.7%, respectively. The 12-week death rate was 27.9%. Disease control and response rate were significantly lower in patients with liver metastases. Platinum sensitivity (to first-line treatment), metastatic burden, and lactate dehydrogenase (LDH) showed prognostic impact on survival in univariate analysis. Neutrophil-to-lymphocyte ratio (NLR) was a significant and independent predictor of survival in univariate ( p = 0.01) and multivariate analyses [hazard ratio (HR), 2.1; 95% CI = 1.1–4.1; p = 0.03]. Conclusion: CPI in patients with relapsed or refractory (R/R) SCLC is of limited value in an overall patient cohort; however, long-term survival, in particular with CPI combination strategies, is possible. Clinical characteristics allow a more differentiated subgroup selection, in particular patients with low NLR showed less benefit from CPI in R/R SCLC.

In this exploratory prospective observational study on 40 small cell lung cancer (SCLC) patients treated with a combination of chemotherapy and immune checkpoint inhibitors, blood immune cells were characterized by multi-color flow cytometry at the baseline and at the third therapy cycle. The numbers of neutrophils and of T-, B-, and NK cells, as well as the frequency of HLA-DR^low monocytes, 6-SulfoLacNAc (slan)+ non-classical monocytes and circulating dendritic cell (DC) subtypes were determined. The prognostic value of the parameters was evaluated by the patient’s survival analysis with overall survival (OS) as the primary endpoint. In addition, blood cell parameters from SCLC patients were compared to those from non-SCLC (NSCLC). The global median OS of patients was 10.4 ± 1.1 months. Disease progression (15% of patients) correlated with a higher baseline neutrophil/lymphocyte ratio (NLR), more HLA-DR^low monocytes, and lower NK cell and DC numbers. The risk factors for poor OS were the presence of brain/liver metastases, a baseline NLR ≥ 6.1, HLA-DR^low monocytes ≥ 21% of monocytes, slan+ non-classical monocytes < 0.12%, and/or CD1c+ myeloid DC < 0.05% of leukocytes. Lymphocytic subpopulations did not correlate with OS. When comparing biomarkers in SCLC versus NSCLC, SCLC had a higher frequency of brain/liver metastases, a higher NLR, the lowest DC frequencies, and lower NK cell numbers. Brain/liver metastases had a substantial impact on the survival of SCLC patients. At the baseline, 45% of SCLC patients, but only 24% of NSCLC patients, had between three and five risk factors. A high basal NLR, a high frequency of HLA-DR^low monocytes, and low levels of slan+ non-classical monocytes were associated with poor survival in all lung cancer histotypes. Thus, the blood immune cell signature might contribute to a better prediction of SCLC patient outcomes and may uncover the pathophysiological peculiarities of this tumor entity.

Although immune checkpoint inhibitor (ICI) therapies have improved the treatment of patients with advanced non-small cell lung cancer (NSCLC), several patients do not achieve durable clinical responses. Biomarkers for the prediction of therapy responses are urgently needed. To identify blood cell parameters correlating with patients’ survival, immune cells from 90 patients with NSCLC undergoing a combination of ICI and chemotherapy were prospectively monitored. At the time point of the first and third antibody administration, complete leukocyte blood count, the percentage of HLA-DR^low monocytes, the percentage of 6-Sulfo LacNAc (slan)+CD16+ non-classical monocytes, and the number of circulating dendritic cell (DC) subtypes, as well as T-, B-, and NK cells were determined by multi-color flow cytometry in peripheral blood. The prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis, with progression-free survival (PFS) as the main criterion. A total of 67 patients (74.4%) showed a partial remission or a stable disease, and 35% of patients even survived 12 months and longer. Patients with a neutrophil-to-lymphocyte ratio (NLR) ≥6.1, a frequency of HLA-DR^low monocytes ≥22%, of slan+ non-classical monocytes <0.25% of leukocytes, and/or a sum of myeloid DC (MDC) and plasmacytoid DC (PDC) ≤0.14% of leukocytes had a poorer prognosis. The hazard ratio for PFS was 2.097 (1.208–3.640) for the NLR, 1.964 (1.046–3.688) for HLA-DR^low monocytes, 3.202 (1.712–5.99) for slan+ non-classical monocytes, and 2.596 (1.478–4.56) for the MDC/PDC sum. Patients without any of the four risk factors showed the best PFS. Furthermore, low NK cell counts correlated with shorter PFS (cutoff 200 cells/µL). Female patients had lower baseline NK cell counts and a shorter PFS. Our study confirms the usefulness of blood immune cells as biomarkers for clinical response and survival in NSCLC patients undergoing a combined ICI/chemotherapy.

Introduction: Lung cancer is most common in older patients; despite this, older patients are historically under-represented in clinical studies. Here we present data from GIDEON, a study undertaken in Germany in patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) receiving first-line afatinib. GIDEON enrolled a high proportion of patients aged >= 70 years, providing an opportunity to study afatinib use in older patients.Materials and Methods: In GIDEON (NCT02047903), a prospective non-interventional study, patients with EGFRm+ NSCLC received first-line afatinib in routine clinical practice until disease progression, death or intolerable adverse events. Key objectives were twelve-month progression-free survival (PFS) rate and objective response rate (ORR). Overall survival (OS) and safety were also assessed. This post hoc analysis explores out-comes of patients grouped by age (>= 70 and = 70 years. In the >= 70 years age group and the = 70 years age group and the = 3 adverse drug reactions (ADRs) were observed in 34.8% and 40.7% of patients, respectively; the most common were diarrhea (13.6% and 14.0%), acneiform dermatitis (7.6% and 7.0%), stomatitis (1.5% and 4.7%) and maculopapular rash (1.5% and 4.7%).Discussion: Patients with EGFRm+ NSCLC aged >= 70 years showed clinical benefit from first-line afatinib with no unexpected safety signals, supporting the use of afatinib in this setting.

Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: In this retrospective single-center study, we analyzed clinical data from 72 patients with stage III NSCLC treated with definitive CRT between 2017 and 2022. The patients were stratified by receipt of durvalumab consolidation. Univariable and multivariable Cox regression models were used to assess overall survival (OS) and progression-free survival (PFS). Stepwise variable selection based on the Akaike Information Criterion (AIC) was used to construct an optimized multivariable model. A sensitivity analysis with adjustment for treatment period (2017–2018 vs. 2019–2022) was conducted to account for the introduction of durvalumab into routine clinical practice. Results: Among 72 patients, 35 received durvalumab and 37 did not. The median OS was 2.08 years; the 3- and 5-year OS rates were 38.6% and 30.3%, respectively. Multivariable regression revealed significantly improved OS associated with Karnofsky performance status (KPS) > 80% (HR 0.29, p = 0.003), Charlson Comorbidity Index (CCI) ≤ 2 (HR 0.39, p = 0.009), and durvalumab treatment (HR 3.99, p = 0.008). PD-L1 expression ≥ 1% showed a trend toward improved OS (HR 3.72, p = 0.063). The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, respectively. Patients treated with durvalumab had a longer median PFS (20.5 months) compared to those without durvalumab (12.0 months). In the multivariable analysis, KPS > 80% (HR 0.29, p < 0.001), CCI ≤ 2 (HR 0.53, p = 0.048), and durvalumab treatment (HR 2.81, p = 0.023) were significantly associated with improved PFS. A sensitivity analysis adjusting for treatment period—reflecting the introduction of durvalumab into routine clinical practice from 2019—confirmed the robustness of these findings. Conclusions: Our findings support the clinical benefit of durvalumab consolidation following CRT in a real-world population, especially in patients with good performance status and low comorbidity burden. These results confirm and extend the PACIFIC trial findings into routine clinical practice, highlighting the prognostic value of functional status and comorbidity alongside PD-L1 expression.