Characterization of host immune cell parameters before and during immunotherapy is expected to identify predictive biomarkers for clinical outcome. We prospectively monitored blood immune cells from 35 patients with advanced non–small cell lung cancer undergoing checkpoint inhibitor monotherapy. The aim was to identify parameters correlating with better/worse outcome. Peripheral blood was serially collected before each infusion at the onset and at cycle 3 and 5 of immunotherapy. A complete leukocyte blood count, the lymphocytic subpopulations and the percentages of both HLA-DRlow monocytes and dendritic cells (DC) were monitored. Disease control was defined as partial/complete response and stable disease on computed tomography scan according to RECIST 1.1. The predictive value of the immune cell parameters investigated was evaluated by patients’ survival analysis. Forty percent of patients showed a clinical response, and the global median overall survival was 7.0 months (95% confidence interval: 3.5–10.5). Patients with an initial neutrophil-to-lymphocyte ratio (NLR) ≥5.2, and/or an amount of HLA-DRlow monocytes ≥11% and/or a total DC level ≤0.4% of leukocytes did rarely respond to PD-1 inhibitor therapy. Otherwise, the immunotherapy-induced decrease of the neutrophil-to-lymphocyte ratio and/or HLA-DRlow monocytes and the increase of total DC frequencies were correlated with improved therapy response and prolonged overall survival. Blood values in the third cycle of immunotherapy did already reflect the effects observed. On the basis of the 3 immune cell parameters identified we created 3 different variants of scores that enable to stratify patients into groups of risk/therapy response. Our results warrant further investigation in larger prospective clinical trials for validation.
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.
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.
Introduction Patients with lung adenocarcinoma not expressing TTF1 and those with a KRAS mutation have worse prognosis. However, available data are limited and sometimes contradictory. Therefore, this retrospective cohort analysis aimed to clarify whether there was a difference in overall survival and progression-free survival between these groups of patients. Methods In total, data derived from 181 patients with metastatic lung adenocarcinoma treated at the Martha-Maria Halle-Dölau Hospital from 2016 to 2019 were analyzed. Kaplan-Meier curves were generated, and associated values, such as median survival and its confidence intervals, were determined using the log-rank test. Results A benefit in overall survival (OS) (8.4 vs 5.8 months; HR, .8; 95% CI, .53-1.19; P = .267) was associated with positive TTF1 expression, but this was not statistically significant. The same trend was shown with the progressive free survival (PFS) (6.5 vs 4.6 months; HR, .76; 95% CI, .51-1.20; P = .162). In patients with a KRAS mutation, there was no difference in OS compared to those with a wildtype KRAS. The median survival was almost identical at 7.5 months ( KRAS mutation, 95% CI, 3.32-11.74) and 7.0 months ( KRAS wildtype, 95% CI, 3.59-10.41). Additionally, in PFS, there was no difference between the 2 groups (5.8 vs 6.3 months). Conclusions Our analysis did not show a worse prognosis in patients with a KRAS mutation or in those with missing TTF1 expression, which is most likely related to the new therapeutic options. As a result of the administration of immunotherapy in patients with a KRAS mutation and the change from a regimen containing pemetrexed to a regimen containing no pemetrexed, the corresponding patients no longer seem to have a worse prognosis.
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