Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors

Abstract

BackgroundSteroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs.MethodsWe reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation.ResultsOut of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation.ConclusionsIn patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.

Comparisons between tumor burden and other prognostic factors that influence survival of patients with non‐small cell lung cancer treated with immune checkpoint inhibitors

“…Finally, this study did not include analysis related to steroid use. Baseline steroid use in a similar study setting has been previously reported to be a negative prognostic factor . However, during the observation period of this study, no patient received concurrent systemic corticosteroids (equivalent to greater than 10 mg of prednisone per day) during ICI therapy as a result of our institutionally established local ICI dosing criteria.…”

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study

“…Several recent studies assessed the effect of early steroid use on clinical outcomes when steroids were prescribed for several medical conditions, such as dyspnea, pain, fatigue, brain metastases, or spinal cord compression . In a pooled cohort of 640 patients receiving an anti–PD‐1/PD‐L1 agent for non–small cell lung cancer, 90 patients (14%) received prednisone equivalent ≥10 mg at ICI initiation.…”

“…Patients receiving steroids at baseline have more aggressive disease, with a bias that could persist even after adjustment for cofounding variables . Fucà et al studied 35 patients who received early treatment with steroids, defined as corticosteroids ≥10 mg for at least 1 day within 28 days after ICI initiation, among 151 patients receiving ICIs for non–small cell lung cancer (96% of whom were treated with an anti–PD‐1/PD‐L1 agent). Patients in the exposed cohort had a lower probability of achieving disease control (OR 0.32, P = 0.006), and had shorter progression‐free survival (HR 1.88, P = 0.03) and overall survival (HR 2.38, P < 0.001) after adjustment for other confounding covariates.…”

“…Patients in the exposed cohort had a lower probability of achieving disease control (OR 0.32, P = 0.006), and had shorter progression‐free survival (HR 1.88, P = 0.03) and overall survival (HR 2.38, P < 0.001) after adjustment for other confounding covariates. Steroids could impair the early T cell signature, which has been shown to be associated with the response to ICIs in biopsy specimens obtained from melanoma patients soon after treatment initiation, but when used later could have less impact, as shown in several studies . Whether other causes of immunodepression, such as primary immunodeficiencies or chronic HIV infection, could dampen the efficacy of ICI is not known and should be studied.…”

Is Immune Checkpoint Inhibitor Treatment an Option for Patients With Rheumatic Diseases and Cancer?

“…Tison and colleagues report an association between use of an immunosuppressant at the start of ICI therapy and shorter progression‐free survival from cancer, with a trend toward shorter overall survival. Early prednisone use (>10 mg per day within 28 days of ICI treatment) has been associated with worse tumor control, progression‐free survival, and overall survival in patients with metastatic non–small cell lung cancer receiving ICIs . However, in the study by Tison et al, early use of glucocorticoids was also associated with the presence of brain metastases and other cancer‐related symptoms, raising a concern that early use was associated with more advanced disease, increasing the possibility of bias by confounding.…”