Table 4.

Interim recommendations for management of FN in patients with cancer receiving chemotherapy during the coronavirus (COVID-19) pandemic.

Society	Recommendations
ASCO27	• G-CSF should be used cautiously and in line with guidelines from ASCO • To avoid neutropenia or myelosuppression, which may put the patient at higher risk of COVID-19 infection, prophylactic G-CSF would still be justified • Limited/no data available in patients with active COVID-19 needing G-CSF for neutropenia/FN • Decisions need to be based on the clinical situation • Regarding COVID-19, ASCO identifies 2 key areas of management of patients with potential FN: ◦ Prophylaxis—potential use of G-CSF in patients at a lower level of expected risk (eg, >10% risk) in order to reduce the risk of FN and emergency care; neutrophil count monitoring and regular contact advised ◦ Acute care—for patients with potential FN, evaluation of status should occur by phone/telemedicine to determine if the patient should be assessed in the clinic or sent to the ED. For those with known FN, standard guidelines46 for care (including isolation) should be followed irrespective of COVID-19 status. If available, rapid COVID-19 testing should be used to ascertain the level of PPE required for caregivers as well as the appropriate facility location for continued care. If rapid testing is unavailable, the patient should be managed for FN per standard guidelines with the assumption of COVID-19 infection
NCCN29	• Recommendations aim to minimize risk of hematologic complications associated with chemotherapy, reducing the need for hospital occupancy or additional infusion clinic/ED visits • Recommended that routine prophylactic G-CSF should be made available to all patients receiving intermediate- or high-risk chemotherapy regimens • Prophylactic G-CSFs may also be appropriate in patients receiving low-risk regimens when age or comorbidities increase their risk of FN • For patients experiencing FN who have not received prior prophylactic therapy with PEGylated G-CSFs, it is advised they start G-CSFs to shorten time to neutrophil recovery • For patients with respiratory infection, respiratory symptoms, or a confirmed/suspected COVID-19 infection and FN, G-CSF is not recommended due to the potential for increasing pulmonary inflammation and inflammatory cytokine (eg, IL-6) production associated with severe COVID-19 infection • Self-administration of daily filgrastim or long-acting pegfilgrastim (1-3 days after chemotherapy) or use of an on-body injector pegfilgrastim are recommended to minimize visits to outpatient centers and reduce the risk of COVID-19 exposure
ESMO28	• For patients with solid tumors not treated for cure, consider administering regimens at low risk of FN ◦ For use of regimens with a higher risk of FN, there must be considerable evidence that clearly outweighs potential emergency intervention and COVID-19 exposure • G-CSF indication should be expanded to include patients receiving chemotherapy with a lower risk of FN (the theoretical concern of acute respiratory failure due to G-CSF-induced leukocyte recovery in patients with COVID-19 pulmonary infection does not outweigh the benefit); however, this approach may require additional outpatient clinic visits • For outpatient management of FN in patients with lower risk, well-documented and verified criteria are available (eg, the MASCC FN risk group stratifications47), with published randomized trials using oral antibiotics • Use of antibiotic prophylaxis and/or prescription of stand-by antibiotics should be expanded due to a potential risk of a delay to emergency visits for patients who develop fever • Critical review and reduction of the use of steroids is recommended, if possible • In patients receiving a fluoropyrimidine, genetic testing to identify patients with DPD deficiency is recommended48 • No evidence is currently available demonstrating that neutropenia due to PARP or CDK4/6 inhibitors results in an increase in associated viral infections

ASCO, American Society of Clinical Oncology; CDK, cyclin-dependent kinase; COVID-19, coronavirus disease 2019; DPD, dihydropyrimidine dehydrogenase; ED, emergency department; ESMO, European Society for Medical Oncology; FN, febrile neutropenia; G-CSF, granulocyte colony-stimulating factor; IL-6, interleukin 6; MASCC, Multinational Association of Supportive Care in Cancer; NCCN, National Comprehensive Cancer Network; PARP, poly(adenosine diphosphate-ribose) polymerase; PEG, polyethylene glycol; PPE, personal protective equipment.