Two decades of pegfilgrastim: what have we learned? Where do we go from here?

AbstractChemotherapy-induced febrile neutropenia (FN) is a medical emergency that may occur in patients with malignancies receiving myelosuppressive chemotherapy. FN requires early therapeutic intervention since it is associated with increased hospitalizations and high mortality risk of 5%–20%. FN-related hospitalizations are higher in patients with myeloid malignancies than in those with solid tumors due to the myelotoxicity of chemotherapy regimens and the compromised bone marrow function. FN increases the burden of cancer by causing chemotherapy dose reductions and delays. The administration of the first granulocyte colony-stimulating factor (G-CSF) filgrastim reduced the incidence and duration of FN in patients undergoing chemotherapy. Filgrastim later evolved into pegfilgrastim, which has a longer half-life than filgrastim and is associated with a lower rate of severe neutropenia, chemotherapy dose reduction, and treatment delay. Nine million patients have received pegfilgrastim since its approval in early 2002. The pegfilgrastim on-body injector (OBI) is an innovative device facilitating the time-released auto-injection of pegfilgrastim approximately 27 h after chemotherapy, as clinically recommended for the prevention of FN, thus eliminating the need for a next-day hospital visit. Since its introduction in 2015, one million patients with cancer have received pegfilgrastim using the OBI. Subsequently, the device was approved in the United States (US), European Union, Latin America, and Japan, with studies and a postmarketing commitment demonstrating device reliability. A recent prospective observational study conducted in the US demonstrated that the OBI substantially improved the adherence to and compliance with clinically recommended pegfilgrastim therapy; patients receiving pegfilgrastim via the OBI experienced a lower incidence of FN than those receiving alternatives for FN prophylaxis. This review discusses the evolution of G-CSFs leading to the development of the OBI, current recommendations for G-CSF prophylaxis in the clinic, continued evidence supporting next-day pegfilgrastim administration, and improvements in patient care made possible with the OBI.PLAIN LANGUAGE SUMMARYFor over 20 years, treatment with pegfilgrastim (a therapy that supports the growth of immune cells) has been used in patients with cancer to prevent febrile neutropenia (FN) – an unwanted effect of cancer treatment or chemotherapy. FN is defined as the loss of healthy immune cells and development of fever possibly due to an infection. Patients with FN may be very ill or may die, depending on the seriousness of the condition. However, treatment with pegfilgrastim reduces the occurrence of FN and improves survival.Treatment guidelines recommend that pegfilgrastim should be given 24 h after chemotherapy, requiring patients to travel to the hospital on the next day of chemotherapy. Some patients may choose the less helpful option of receiving pegfilgrastim on the same day of chemotherapy to avoid travel. This need led to the development of an on-body injector (OBI) device that is applied on the skin on the last day of chemotherapy and administers pegfilgrastim approximately 27 h after chemotherapy. The highly reliable OBI ensures timely delivery of therapy with a success rate of 99.9%, reduces the travel burden, and helps in following the recommended guidelines for pegfilgrastim administration. For two decades, pegfilgrastim has played a significant role in the treatment and prevention of FN, and the new OBI device provides the required treatment support for improving patient care.Keywords: Febrile neutropeniaon-body injectorpegfilgrastimdevice reliabilityprophylaxisG-CSF TransparencyDeclaration of fundingThis work was funded by Amgen Inc., Thousand Oaks, CA, USA.Declaration of financial/other relationshipsThe authors declare the following financial interests or personal relationships which may be considered as potential competing interests: JC reports the role of Scientific Advisor for G1 Therapeutics and Sandoz. CB, SL, and DS are employed by and own stock in Amgen.Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contributionsCB, SL, and DS were involved in the conception of this manuscript. CB, SL, DS, and JC were involved in the design, interpretation, and critical revision of this manuscript for intellectual content. All authors approve this version of the review for publication.AcknowledgementsThe authors thank Yin Lin, PhD, of Amgen Inc. for providing feedback on the manuscript. Medical writing support was provided by Utkarsha A Singh, PhD, of Cactus Life Sciences (part of Cactus Communications Pvt Ltd), funded by Amgen Inc., Thousand Oaks, CA, USA.Data availability statementNot applicable.Notesi Neupogen; Amgen Inc., Thousand Oaks, CAii Neulasta Onpro; Amgen Inc., Thousand Oaks, CA