Study evaluates effect of neutropenia and granulocyte colony-stimulating factor in cancer patients with COVID-19
The potential risks versus benefits of recombinant human granulocyte colony-stimulating factor (G-CSF) administration should be considered in neutropenic cancer patients with coronavirus disease 2019 (COVID-19), since G-CSF administration may lead to worsening clinical and respiratory status, suggests a study published in Clinical Infectious Diseases.
“Neutropenia is a common side-effect of many anti-cancer therapies due to their effects on rapidly dividing hematopoietic cells. Recombinant human G-CSF is often given to cancer patients for ongoing or impending neutropenia,” wrote Allen W Zhang, MD, University of British Columbia, Vancouver, Canada, and colleagues. “However, the clinical impact of neutropenia and G-CSF use in cancer patients with COVID-19 remains unknown.”
To characterise the effect of G-CSF (filgrastim or pegfilgrastim) on the development of respiratory decompensation and death in cancer patients with COVID-19, researchers performed a retrospective cohort study of 379 cancer patients at Memorial Sloan Kettering Cancer Center who tested positive for COVID-19 and received cancer directed therapy within 30 days of their COVID-19 diagnosis between March 11 and November 16, 2020.
Cancer types reported among the patients included breast cancer (24%), colorectal cancer (11%), lung cancer (10%), lymphoma (7%), prostate cancer (7%), among others. Of the patients, 227 (60%) received cytotoxic chemotherapy within 30 days of their COVID-19 diagnosis. Meanwhile, 28 (7.4%) patients received either filgrastim or pegylated filgrastim.
Among the 379 patients, 130 (34.3%) were hospitalised for the management of COVID-19 symptoms. Using an extended Cox model with G-CSF encoded as a time-dependent covariate, the researchers found that G-CSF administration was significantly associated with increased risk of hospitalisation in patients with COVID-19 (hazard ratio [HR] 3.54, 95% confidence interval [CI] 1.25-10.0, P = 0.017). The association remained significant when considering patients who had asymptomatic COVID-19 (HR 18.31, 95% CI 2.51-96.8, P = 0.008).
Similarly, among the 130 patients who were hospitalised, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR 3.56, 95% CI 1.19-10.2, P = 0.024), but not neutropenia (HR 0.95, 95% CI 0.39-2.1, P = 0.907). The researchers observed that this effect was predominantly seen in patients who exhibited a high response to G-CSF based on their absolute neutrophil count (ANC) increase post-G-CSF administration (HR 7.78, 95% CI 2.05-27.9, P = 0.004), compared to those who had less robust levels of response to G-CSF (HR 4.04, 95% CI 0.80-16.7, P = 0.086). Further, the researchers found that the severity of neutropenia (ANC nadir in K/mcL) was not correlated with G-CSF use (Wilcoxon P value 0.55), which ruled out the possibility of G-CSF being reserved for cases with more severe neutropenia.
“To our knowledge, this is the first study describing the course of [COVID-19] in selected cancer patients who received G-CSF for neutropenia,” the authors noted. “We observed a higher risk of hospitalisation, as well as respiratory failure and death in patients that received G-CSF, particularly among patients that had a robust neutrophil response. Our observations on the inpatient side also suggest that neutropenia during COVID-19 illness itself was not an independent risk factor for adverse outcomes in COVID-19.”
“There has recently been accumulating evidence of rapid clinical deterioration in some patients with COVID-19 due to the hyperactive immune response driving COVID-19 progression, causing extensive infiltration of myeloid cells into the lungs (particularly monocytes, macrophages and neutrophils), leading to a cytokine storm,” the authors added. “Considering that neutrophil influx in the lung is a hallmark feature of acute respiratory distress syndrome, and that acute lung injury has already been reported as a potential complication of G-CSF use, administering G-CSF to all cancer patients with COVID-19 may have detrimental clinical consequences.”