Patients were included if they received filgrastim for primary prophylaxis of FN with a curative cancer diagnosis. Patients receiving salvage chemotherapy for hematologic malignancies with intent to proceed to curative transplant were also included. Bone marrow involvement of the tumor is a FN risk factor. Only patients with hematologic malignancies and bone marrow involvement were included. Patients wereexcluded if they received filgrastim for secondary prophylaxis of neutropenia or FN, a noncurative cancer diagnosis, stem cell transplant mobilization and engraftment, or nononcologic neutropenia.
The primary outcome for this study was the incidence of neutropenia or FN leading to treatment delays despite the use of primary prophylaxis with filgrastim. A dose delay was defined as a delay of planned chemotherapy by ≥ 3 days. Secondary outcomes included chemotherapy dose decreases or discontinuations, hospitalizations, days of hospitalization, infections, extended duration of filgrastim, and transitions to pegfilgrastim due to neutropenia or FN. Documented infections were defined in patients with a positive culture, laboratory testing, or imaging consistent with infection. Extended durations of filgrastim or transitions to pegfilgrastim were patient specific and upon clinician discretion.
Descriptive statistics were used to summarize the study population and their health outcomes. Fisher exact test was used to compare FN incidence for high- and intermediate-risk FN groups.
RESULTS
Between September 1, 2015, and September 24, 2020, 381 patients received filgrastim. Of these patients, 59 met the inclusion criteria. Patients receiving filgrastim were excluded due to stem cell transplant mobilization/engraftment (n = 145), a noncurative cancer diagnosis (n = 134), use as a secondary prophylaxis (n = 33), and nononcologic neutropenia (n = 8). Additionally, 2 patients initially received pegfilgrastim and were not included in this data set.
The median (IQR) age was 64 (55-70) years and 42 patients (71%) were male (Table 1).
Ten patients (17%) experienced dose delays despite filgrastim use (Table 2).
Nine patients (15%) had the number of filgrastim injections per chemotherapy cycle extended due to various reasons. Five patients required extended days after hospitalization for FN, 3 patients for dose delays due to neutropenia with the previous cycle, and 1 patient with an undocumented reason outside of the prespecified outcomes. Two of these patients experienced continued neutropenia and dose delays after extending filgrastim from 5 to 7 days or 7 to 10 days. One patient who experienced continued neutropenia after extending filgrastim to 10 days was subsequently transitioned to pegfilgrastim without further episodes of neutropenia. The other patient who still experienced neutropenia after extending filgrastim to 7 days was receiving the last chemotherapy cycle and did not require subsequent doses of filgrastim.
Two additional patients were not included in the hospitalizations. The first was a patient on a chemotherapy regimen with a high risk for FN who presented to the emergency department with documented FN but was never admitted since the patient elected to not be hospitalized. This patient developed oral, anal, and vaginal candidiasis, and it was noted by the oncologist at the next clinic visit that this was likely secondary to grade 4 neutropenia (ANC < 500 neutrophils/μL). The second was a patient on a chemotherapy regimen with an intermediate risk for FN who was already hospitalized but had developed FN and sepsis despite filgrastim use.
Finally, out of the hospitalized patients, 9 (15%) had infections. This included 6 patients (18%) in the high risk for FN group and 3 patients (12%) in the intermediate risk for FN group (P = .72). Six patients transitioned to pegfilgrastim for hospitalization, 2 for neutropenia, and 1 for an unspecified reason. Nine patients (15%) who received filgrastim ended up transitioning to pegfilgrastim; 6 (67%) of these patients were transitioned due to hospitalization for FN. Of all the patients who transitioned to pegfilgrastim, 1 patient on a high risk for FN regimen developed sepsis due to herpes zoster in the setting of neutropenia after the previous cycle of chemotherapy.