Engert, A., Griskevicius, L., Zyuzgin, Y., Lubenau, H., & del Giglio, A. (2009). XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy. Leukemia and Lymphoma, 50, 374–379.

The purpose of the study was to demonstrate the activity and safety of XM02 compared to filgrastim for the prevention of chemotherapy-induced neutropenia in patients with non-Hodgkin lymphoma.

Patients randomized in a 2:1 ratio of XM02 to filgrastim for the first cycle of chemotherapy (CHOP or R-CHOP [rituximab added per national guidelines and physician discretion]). All patients received XM02 in subsequent cycles, with a maximum of six cycles; three weeks per cycle. Subcutaneous injections given daily (5 mg/kg per day) for at least five days and a maximum of 14 days. Drug stopped with the absolute neutrophil count (ANC) of  10 x 10⁹/L or greater after nadir was reached (blood samples to evaluate ANC taken within 24 hours prior to start of chemotherapy and then daily from day 2 on in the first cycle and day 5 on in cycles 2–6 until day 15 or until ANC reached greater than 2.0 x10⁹/L). Body temperature measured daily until day 15 or until ANC reached greater than 2.0 x10⁹/L.

• 92 total patients were in the sample.
• Age ranged from 18-83 years.
• For women, were in the XM02 group and 12 were in the filgrastim group.
• For men, 31 were in the XM02 group and 17 were in the filgrastim group.
• Patients had aggressive NHL, defined as diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, follicular lymphoma grade 3, or anaplastic large cell lymphoma.
• Eligible patients had to be chemotherapy-naïve, have a life expectancy of six months or longer, an international prognostic index score of 3 or lower, an ANC greater than 15 x 10⁹/L, a platelet count greater than 100 x 10⁹/L, and adequate hepatic, cardiac, and renal function for the chemotherapy regimen.

Multiple inpatient and outpatient settings

Active treatment

Phase III, randomized, controlled trial

• Duration of severe neutropenia (DSN)    
• Febrile neutropenia    
• ANC
• Adverse events: musculoskeletal and connective tissue disorders (bone pain, arthralgia, back pain, musculoskeletal pain, jaw pain); general disorders and administration site conditions (pyrexia, fatigue, flu like illness); gastrointestinal (diarrhea); nervous system (HA), vascular (hot flush); and blood and lymphatic (anemia)
• Pharmacokinetics
   

XM02 was found to be pharmacokinetically similar to filgrastim and not statistically significantly different from filgrastim for febrile neutropenia (FN) in cycle 1 (11.1% for XM02 and 20.7% for filgrastim). ANC values in both groups reached a maximum at day 4 and decreased to a nadir on day 9 followed by an increase reaching a maximum on day 11, with a return to day 1 mean values reached on day 21 (similar to other filgrastim studies). Drug-related adverse events were not statistically different between XM02 and filgrastim.

The administration of G-CSFs for the prevention of chemotherapy-induced neutropenia and related adverse events has been proven effective in many trials. Use of XM02 has similar pharmacokinetics, safety, and efficacy compared to the established filgrastim. Other studies show greater efficacy with pegylated filgrastim that requires less dosing than the daily doses of filgrastim. The use of XM02 instead of filgrastrim does not seem favorable based on these results.

• Small sample size (less than 100 participants)
• This study was sponsored and funded by BioGeneriX AG, the manufacturer of XM02.
• Filgrastim was only compared to XM02 in the first chemotherapy cycle, then all patients received XM02; yet the results evaluated outcomes throughout the duration of all chemotherapy doses.
   

Based on this study alone, nurses can be aware that XM02 for patients 18 and older with aggressive NHL for the risk reduction of neutropenia and related adverse outcomes will be similarly effective to filgrastrim.