Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years

Figures & data

Figure 1. Evolution of CSF use in US clinical practice.

Table 1. Currently available CSF agents in US clinical practice.

CSF agent	Brand name	Date approved	Indication
Short-acting agents
Filgrastim	Neupogen	1991	Patients with cancer receiving myelosuppressive chemotherapy Indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with cancer undergoing bone marrow transplantation Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g. febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients undergoing autologous peripheral blood progenitor cell collection and therapy Indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with severe chronic neutropenia Indicated for chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.
Sargramostim	Leukine	1991	• Following induction chemotherapy in acute myelogenous leukemia • Mobilization and following transplantation of autologous peripheral blood progenitor cell • Myeloid reconstitution after autologous bone marrow transplantation • Myeloid reconstitution after allogeneic bone marrow transplantation • Bone marrow transplantation failure or engraftment delay
tbo-Filgrastim	Granix	2012	In adult and pediatric patients 1 month and older for reduction in the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Filgrastim-sndz	Zarxio	2015	Patients with cancer receiving myelosuppressive chemotherapy Indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with cancer undergoing bone marrow transplantation Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g. febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients undergoing autologous peripheral blood progenitor cell collection and therapy Indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with severe chronic neutropenia Indicated for chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.
Filgrastim-aafi	Nivestym	2018	Patients with cancer receiving myelosuppressive chemotherapy Indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever. Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML). Patients with cancer undergoing bone marrow transplantation Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g. febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation. Patients undergoing autologous peripheral blood progenitor cell collection and therapy Indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis. Patients with severe chronic neutropenia Indicated for chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.
Long-acting agents
Pegfilgrastim	Neulasta	2002	To decrease the incidence of infection as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Pegfilgrastim-jmdb	Fulphila	2018	Same as pegfilgrastim
Pegfilgrastim-cbqv	Udenyca	2018	Same as pegfilgrastim
Pegfilgrastim-bmez	Ziextenzo	2019	Same as pegfilgrastim

Table 2. Current recommendations for use of CSF prophylaxis in US clinical practice.

Organizations	Recommendations
American Society of Clinical Oncology	• Primary prophylaxis with a CSF starting with the first cycle and continuing through subsequent cycles of chemotherapy is recommended in patients who have an approximately 20% or higher risk for febrile neutropenia based on patient-, disease- and treatment-related factors. Primary CSF prophylaxis should also be administered in patients receiving dose-chemotherapy when considered appropriate. Consideration should be given to alternative, equally effective, and safe chemotherapy regimens not requiring CSF support when available. • Secondary prophylaxis with a CSF is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy, in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or delay may be a reasonable alternative.
National Comprehensive Cancer Network	• In adult patients with solid tumors and non-myeloid malignancies, primary prophylaxis with CSFs is recommended if overall risk of FN is high (>20%) and is to be considered for patients at intermediate risk (10–20%) with one or more of the following risk factors: prior chemotherapy or radiation therapy; persistent neutropenia; bone marrow involvement by tumor; recent surgery and/or open wounds; liver dysfunction (bilirubin >2.0); renal dysfunction (creatinine clearance <50); and age >65 years receiving full chemotherapy dose intensity. • Secondary prophylaxis is to be considered in patients experiencing FN or a dose-limiting neutropenic event in a prior cycle, if there was no prior use of CSFs. For patients with prior use of CSFs in the prior cycle, chemotherapy dose reduction or change in treatment regimen should be considered. Short-acting agents should be started on the day after myelosuppressive chemotherapy or up to3 or 4 d thereafter. Long-acting agents should be administered the day after myelosuppressive therapy.