ABSTRACT
BackgroundNeutropenia is commonly encountered in cancer patients, and recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) is widely given to oncology patients to counteract neutropenia and prevent infection. G-CSF is both a growth factor and cytokine that initiates proliferation and differentiation of mature granulocytes. However, the clinical impact of neutropenia and G-CSF use in cancer patients, who are also afflicted with coronavirus disease 2019 (COVID-19), remains unknown. MethodsAn observational cohort of 304 hospitalized patients with COVID-19 at Memorial Sloan Kettering Cancer Center was assembled to investigate links between concurrent neutropenia (N=55) and G-CSF administration (N=16) on COVID-19-associated respiratory failure and death. These factors were assessed as time-dependent predictors using an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, a similar model was constructed with patients that received G-CSF, categorized into "high"- and "low"- response, based on the level of absolute neutrophil count (ANC) rise 24 hours after growth factor administration. ResultsNeutropenia (ANC < 1 K/mcL) during COVID-19 course was not independently associated with severe respiratory failure or death (HR: 0.71, 95% Cl: 0.34-1.50, P value: 0.367) in hospitalized COVID-19 patients. When controlling for neutropenia, G-CSF administration was associated with increased need for high oxygen supplementation and death (HR: 2.97, 95% CI: 1.06-8.28, P value: 0.038). This effect was predominantly seen in patients that exhibited a "high" response to G-CSF based on their ANC increase post-G-CSF administration (HR: 5.18, 95% CI: 1.61-16.64, P value: 0.006). ConclusionPossible risks versus benefits of G-CSF administration should be weighed in neutropenic cancer patients with COVID-19 infection, as G-CSF may lead to worsening clinical and respiratory status in this setting.
Subject(s)
COVID-19ABSTRACT
New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center (MSKCC) performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age [≥] 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.