Consensus Recommendations on Pegfilgrastim for Prophylaxis of Febrile Neutropenia

Chemotherapy-induced febrile neutropenia (FN), a side effect of many cancer treatments, can lead to infection, sepsis, and potentially death. Use of granulocyte-colony stimulating factor (G-CSF) agents, including the long-acting G-CSF pegfilgrastim, is recommended for both primary and secondary prophylaxis of chemotherapy-induced FN, and many providers and patients prefer pegfilgrastim to short-acting therapeutic options because of its less frequent administration.

A paper by Matti Aapro, MD, recently published in Supportive Cancer Care, outlined—for the first time—consensus recommendations on using pegfilgrastim in particular patients and therapeutic scenarios. The consensus recommendations were made by an advisory board convened in 2015; experts were selected to participate on the board if they were specialists in oncology or onco-hematology, had extensive clinical experience with short-acting and long-acting G-CSF agents, were fluent speakers of English, and were engaged in clinical research and academic work on chemotherapy-induced FN. Ahead of the panel’s meeting, a literature review was performed to establish the current evidence base on using pegfilgrastim.

The experts adopted the following recommendations and statements through consensus agreement:

• Prevention of chemotherapy-associated FN is not yet optimal. Clinical practice may deviate from clinical guidelines in the use of G-CSF, and high-risk patients may not be treated or may be undertreated.
• When curing disease is the intention of chemotherapy, maintenance of planned dose intensity by using G-CSF to prevent delays should be the standard of care.
• In patients receiving chemotherapy or targeted agents with a FN risk of 20% or greater, pegfilgrastim or short-acting G-CSF should be given for all cycles of chemotherapy.
• In patients receiving chemotherapy or targeted therapy with an FN risk of 10% to 20%, if factors that increase risk suggest that the overall risk of neutropenia-related complications is 20% or greater, the patient should receive pegfilgrastim or short-acting G-CSF.
• In patients with an FN risk of under 10%, if special factors suggest that the overall risk of neutropenia-related complications is 20% or higher, the patient should receive pegfilgrastim or short-acting G-CSF.
• If 11 days of filgrastim treatment will not be used, pegfilgrastim should be given instead. If filgrastim is used, it should be maintained until FN has resolved and neutrophil count has returned to normal.
• Based on the convenience and the potential for greater patient adherence, pegfilgrastim may be preferable to 11 days of filgrastim for prevention of chemotherapy-induced FN.
• Pegfilgrastim is not appropriate for treating patients who are receiving weekly chemotherapy because of the current absence of clinical trial data for this use.
• In patients receiving split-dose chemotherapy, pegfilgrastim administration is recommended 24 hours after the last chemotherapy dose.
• If G-CSF is needed for maintenance of a treatment dose or prevention of FN in patients undergoing palliative treatment, convenience and the potential for greater adherence may favor the use of pegfilgrastim.
• Once initiated, pegfilgrastim should be continued throughout all cycles of chemotherapy.
• Additional trials with G-CSF are necessary in the context of targeted and immunotherapies.
• In patients with multiple myeloma (MM) who need G-CSF, pegfilgrastim can be given in some instances, but filgrastim may have more applications, as it can be given concurrently with some treatment regimens.
• In newly diagnosed patients with acute myeloid leukemia who are receiving induction therapy, filgrastim may be considered. In patients receiving consolidation chemotherapy with the intent to cure, pegfilgrastim may be preferable to filgrastim.
• In patients with lymphoma, chronic lymphocytic leukemia, or MM who are receiving targeted treatments, either pegfilgrastim or short-acting G-CSF may be considered.

On some topics—including whether pegfilgrastim or filgrastim is more appropriate in patients with bone pain, or what use of pegfilgrastim is most appropriate for patients with renal impairment—the panel was unable to reach a consensus.

The authors of the paper also note that biosimilar products are increasingly used for the prevention of FN; in both the United States and Europe, biosimilars of short-acting G-CSF agents are available. However, a biosimilar pegfilgrastim therapy has not yet received regulatory approval from either the FDA or the European Medicines Agency.