Biosimilar, Follow-On Filgrastim Feature in New Research on FN and Peripheral Stem Cell Mobilization

Research published in conjunction with the 2018 American Society of Clinical Oncology Annual Meeting presented new findings on the use granulocyte-colony stimulating factor (G-CSF) agents in treating febrile neutropenia (FN) and in peripheral stem cell mobilization.

Differences in AEs with G-CSFs may be due to differing baseline characteristics

G-CSF agents are widely used to treat and prevent chemotherapy-induced FN, and a study published in abstract examined characteristics of patients receiving reference filgrastim (Neupogen), the FDA-approved biosimilar filgrastim (Zarxio), and the FDA-approved follow-on filgrastim (tbo-filgrastim, which was approved prior to the establishment of a US biosimilar regulatory pathway) together with adverse events (AEs).¹

In total, 5470 patients were included, with 4155 receiving reference filgrastim, 771 receiving tbo-filgrastim, and 544 receiving biosimilar filgrastim.

Patients who received the reference were more likely to be male (45%) than were patients who received the follow-on (40%) or the biosimilar (36%), and they were more likely to have a diagnosis of leukemia than other cancers.

Patients who received the follow-on were more likely to experience the following AEs than those who received the reference: cough (5.4%, 3.4%), dizziness (3.0%, 1.3%), dyspnea (9.5%, 7.2%), fatigue (10.2%, 7.1%), and thrombocytopenia (15.6%, 12.7%).

Patients receiving the biosimilar had lower rates of the following AEs than patients who received the reference: arthralgia (0.9%, 3.4%), anemia (18.6%, 24.8%), fatigue (4.2%, 7.1%), and thrombocytopenia (7.9%, 12.7%). However, those receiving the biosimilar had higher rates of dizziness than those receiving the reference (3.1%, 1.3%).

The researchers state that the differences in demographic and clinical characteristics of the patients who received each of the 3 products could be due to differences in cancer type and age, or factors such as provider preferences and reimbursement policies; as the safety profiles of the products are similar, the differences in rates of AEs may explained by differences in the baseline characteristics of the patients.

Using biosimilar filgrastim could lead to faster neutrophil and platelet engraftment

In addition to its use in preventing FN, biosimilar filgrastim, Zarxio, is also approved for peripheral stem cell mobilization.

A retrospective analysis compared the efficacy of the biosimilar with that of reference filgrastim for peripheral stem cell mobilization, and found no difference in the yield of CD34+ cells in patients who received the 2 treatments.² However, using the biosimilar resulted in a significantly shorter time to neutrophil and platelet engraftment.

The study analyzed patients with multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma who were undergoing autologous hematopoietic stem cell transplantation at a single center from 2015 to 2017. All patients had peripheral blood stem cell mobilization with subcutaneous doses of 10 µg/kg per day of either the biosimilar or the reference filgrastim at on days 1 to 5 (with apheresis performed on day 5).

In total, 80 patients were included; 25 received the biosimilar and 55 received the reference filgrastim.

The median yield of CD34+ cells per kg for patients receiving the biosimilar versus the reference was similar at 5.19 (±3.02) and 4.58 (±2.43), respectively (P =.34). However, the median number of days to neutrophil engraftment was 10.8 (±1.78) for the biosimilar group and 12.0 (±2.83) for the reference group (P =.57), and the median number of days to platelet engraftment was 16.8 (±4.13) for the biosimilar group and 19.7 (±5.09) for the reference group (P =.02).

The researchers say that these finding should be confirmed by a large, randomized controlled trial, as engraftment is key in transplantation.

References

1. Irwin DE, Brady BL. Adverse events with G-CSF for neutropenia in cancer. J Clin Oncol. 2018;36 (suppl; abstr e18762).

2. Young D, Reddy PS, Mattar BI, et al. A retrospective analysis comparing efficacy of filgastrim-sndz versus filgastrim for autologous, peripheral stem cell mobilization in patients with multiple myeloma and lymphoma. J Clin Oncol. 2018;36 (suppl; abstr e19505).