Comparison of different types of G-CSF

Granulocyte colony-stimulating factor (G-CSF) is a blood growth factor naturally found in the body. G-CSF stimulates the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils. Under stress, such as infection, high doses of chemotherapy and inflammation can stimulate G-CSF production, which in turn stimulates neutrophil production in the bone marrow and mobilises the neutrophils throughout the body.

Neutrophils are short-lived granulocytes produced in the bone marrow from common myeloid progenitor cells. Neutrophils compromise the majority of white blood cells. Neutrophils ingest, kill and digest pathogens. It helps the immune system fight infections and heal injuries.

A common side effect of chemotherapy is neutropenia, as chemotherapy targets rapidly dividing cells such as myeloblasts, which are the precursor to neutrophils. Since neutrophils are crucial to fighting infections, patients undergoing chemotherapy can be at risk of febrile neutropenia. Febrile neutropenia is a life-threatening condition where patients experience a fever greater than 38.3°C and an absolute neutrophil count of less than 0.5 x 10⁹ cells/L. Patients with febrile neutropenia are required to be hospitalised, and IV antibiotics are administered.

The discovery of G-CSF in the body and its isolation has led to the development of exogenous G-CSF, starting with filgrastim. G-CSF injections can be used to accelerate the proliferation and differentiation of progenitor cells. This rapidly results in more neutrophils available, which shortens the neutropenia phase. Recombinant G-CSF injections reduce the risk of febrile neutropenia by increasing neutrophil count. There are many indications for G-CSF, which include reducing the risk and duration of neutropenia after chemotherapy, mobilisation of stem cells for transplantation and severe chronic neutropenia.

There are three types of G-CSF injections currently readily available, which are pegfilgrastim, filgrastim and lipegfilgrastim.

Pegfilgrastim

Pegfilgrastim is given as a single dose of 6mg subcutaneously. Pegfilgrastim is a pegylated form of filgrastim, which has a longer half-life and lower renal clearance compared to filgrastim. Pegfilgrastim is given at least 24 hours after a chemotherapy cycle, and is usually only required once each chemotherapy cycle. It is usually given 1 to 3 days after completion of chemotherapy.  It is recommended to give chemotherapy only after 14 days from the last pegfilgrastim injection. There is a risk of severe thrombocytopenia if pegfilgrastim is given with concurrent chemotherapy. A common side effect patients experience is bone pain, which also indicates that the medication is working. Patients can take paracetamol to help with the pain. A rare adverse effect which can be fatal if not treated is splenic rupture, which presents as left upper abdominal pain or shoulder pain. Hence patients should be counselled about the difference in pain experienced. Compared to daily filgrastim injections, pegfilgrastim is more convenient to use for patients.

Filgrastim

Compared to the other two, filgrastim is given as a daily injection. Unlike the other two, filgrastim is non pegylated. It can be given as a subcutaneous or intravenous injection. The usual dose is 5-10mcg/kg and rounded up to the nearest vial or syringe size for adults which is given over several days. Chemotherapy is safe to give 24 hours after filgrastim injections. Per eviQ guidelines, filgrastim is used for peripheral blood stem cell mobilisation for use in allogeneic peripheral blood progenitor cell transplantation.

Lipegfilgrastim

Lipegfilgrastim is also given as a single dose of 6mg via subcutaneous injection 24 hours after chemotherapy. It is also a pegylated form of filgrastim and is long acting. Lipegfilgrastim has a longer half-life compared to pegfilgrastim. It has been shown to induce a longer lasting increase in neutrophil counts and a greater time-dependent resistance to neutrophil elastase degradation compared to pegfilgrastim. However, from studies, it is shown to be non-inferior to pegfilgrastim. The side effects are also similar to the others, with bone pain being the most common side effect.