A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis

Abstract

Background: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. Methods: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. Results: Among the 943 cancer patients screened, 83 patients (11,3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1,4, 95% CI [1, 1, 03, 92], p-value = 0.01). Conclusions: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.

ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19

“…However, leucocytosis was common in the treatment arm, including severe cases. We note, that our results and the trial are in stark contrast to observational studies associating higher G-CSF plasma levels 68,69 and rhG-CSF treatment among cancer patients with a poor prognosis 70,71 , likely explained by the inability to distinguish cause and effect. We further emphasize, that our genetically anchored drug prioritisation approach cannot make any recommendations about the best timepoint and dose of intervention during the course of infection/disease, which are crucial parameters for any drug application.…”

G-CSF zur Prophylaxe der Neutropenie und der febrilen Neutropenie, Anämie bei Krebserkrankung

“…Bei Patienten mit aktiver COVID-19-Erkrankung und gleichzeitiger G‑CSF-Therapie kann sich der klinische Zustand verschlechtern [ 23 , 24 ]. Da die Lungenschädigung bei COVID-19 aus einer hyperinflammatorischen Reaktion des Immunsystems resultiert, an der auch Neutrophile beteiligt sind, sollte G‑CSF in dieser Situation vermieden werden [ 25 ].…”

G-CSF zur Prophylaxe der Neutropenie und der febrilen Neutropenie, Anämie bei Krebserkrankung

“…Bei Patienten mit aktiver COVID-19-Erkrankung und gleichzeitiger G‑CSF-Therapie kann sich der klinische Zustand verschlechtern [ 32 , 33 ]. Da die Lungenschädigung bei COVID-19 aus einer hyperinflammatorischen Reaktion des Immunsystems resultiert, an der auch Neutrophile beteiligt sind, sollte G‑CSF in dieser Situation vermieden werden [ 34 ].…”

“…EORTC(European Organisation for Research and Treatment of Cancer)-Leitlinien empfehlen auf Basis randomisierter Studien einheitlich, G‑CSF bei einem FN-Risiko von 20 % oder mehr einzusetzen. Diese Studien zeigen hinsichtlich der Rate an FN und tödlichen Infektionen, dass Patienten mit einem FN-Risiko ≥20 % von G‑CSF signifikant profitieren [ 38 , 39 , 40 , 41 , 42 , 33 ].…”