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
Importance: New York City is a global epicenter for the SARS-CoV-2 outbreak with a significant number of individuals infected by the virus. Patients with multiple myeloma have a compromised immune system, due to both the disease and anti-myeloma therapies, and may therefore be particularly susceptible to coronavirus disease 2019 (COVID-19); however, there is limited information to guide clinical management. Objective: To assess risk factors and outcomes of COVID-19 in patients with multiple myeloma. Design: Case-series. Setting: Five large academic centers in New York City. Participants: Patients with multiple myeloma and related plasma cell disorders who were diagnosed with COVID-19 between March 10th, 2020 and April 30th, 2020. Exposures: Clinical features and risk factors were analyzed in relation to severity of COVID-19. Main Outcomes and Measures: Descriptive statistics as well as logistic regression were used to estimate disease severity reflected in hospital admissions, intensive care unit (ICU) admission, need for mechanical ventilation, or death. Results: Of 100 multiple myeloma patients (male 58%; median age 68, range 41-91) diagnosed with COVID-19, 74 (74%) were admitted; of these 13 (18%) patients were placed on mechanical ventilation, and 18 patients (24%) expired. None of the studied risk factors were significantly associated (P>0.05) with adverse outcomes (ICU-admission, mechanical ventilation, or death): hypertension (N=56) odds ratio (OR) 2.3 (95% confidence interval [CI] 0.9-5.9); diabetes (N=18) OR 1.1 (95% CI 0.3-3.2); age >65 years (N=63) OR 2.0 (95% CI 0.8-5.3); high dose melphalan with autologous stem cell transplant <12 months (N=7) OR 1.2 (95% CI 0.2-7.4), IgG<650 mg/dL (N=42) OR=1.2 (95% CI 0.4-3.1). In the entire series of 127 patients with plasma cell disorders, hypertension was significantly associated with the combined end-point (OR 3.4, 95% CI 1.5-8.1). Conclusions and Relevance: Although multiple myeloma patients have a compromised immune system due to both the disease and therapy; in this largest disease specific cohort to date of patients with multiple myeloma and COVID-19, compared to the general population, we found risk factors for adverse outcome to be shared and mortality rates to be within the higher range of officially reported mortality rates.