Study Shows Low Incidence of Immunogenicity With Tbo-Filgrastim

Neutropenia, a primary cause of delays, interruptions, and dose reduction to chemotherapy, can compromise both patient survival and complete response rates. Granulocyte colony-stimulating factors (G-CSFs), including tbo-filgrastim (Granix), can reduce the incidence, duration, and severity of febrile neutropenia in patients who are receiving chemotherapy. However, drugs like tbo-filgrastim (a follow-on filgrastim product that was approved before the United States had instituted a regulatory pathway for the approval of biosimilar products under the Biologics Price Competition and Innovation Act) can cause serious immune reactions.

The production of anti-drug antibodies (ADAs) can have negative consequences for patients, including such reactions as anaphylaxis, reduced efficacy, and the neutralization of endogenous counterparts by cross-reactive neutralizing antibodies. A new study, conducted by Linglong Zou, PhD, and colleagues, evaluates the immunogenicity of tbo-filgrastim in patients receiving chemotherapy for solid and hematologic malignancies.¹ The research team’s data will be presented at the American Society of Hematology’s 59th Annual Meeting and Exposition in Atlanta, Georgia, on Sunday, December 10, 2017.

Zou and his team collected blood samples during 3 different phase 3 clinical studies that compared the efficacy and safety of tbo-filgrastim with filgrastim and/or placebo administered 1 day after chemotherapy for a duration of 5 to 14 days. The team implemented a 3-tier approach—including screening, confirmation, and a titer assay—to evaluate binding ADAs for tbo-filgrastim using a validated homogeneous enzyme-linked immunosorbent assay. Neutralizing activity was assessed for confirmed-positive ADA test samples using a validated cell-based proliferation assay. Clinical measures were examined for all patients who had confirmed ADAs in order to assess a possible correlation between ADAs and the potential clinical impact of immunogenicity.

In total, 436 patients who had been diagnosed with cancer and who had received tbo-filgrastim were assessed for immunogenicity of the follow-on filgrastim product. These patients had breast cancer (n = 213), lung cancer (n = 160), and non-Hodgkin’s lymphoma (n = 63).

Only 3 patients with breast cancer developed ADAs at a low titer, and none of the samples showed cross-reactivity to endogenous G-CSF or neutralizing antibody activity. Three patients with lung cancer developed ADAs at a low titer, but none of the ADA-positive samples cross-reacted with endogenous G-CSF, and 1 pre-dose sample showed neutralizing antibody activity in cycle 1 prior to tbo-filgrastim treatment. Among the patients with non-Hodgkin’s lymphoma, 1 patient developed ADAs at a titer too low to be determined. No cross-reactivity or neutralizing antibody activity were associated with this patient’s blood sample. Overall, immunogenicity incidence was 1.6% among all of the patients tested, and none of the patients with positive ADA samples showed evidence of hypersensitivity, anaphylaxis, or a loss of treatment efficacy.

The researchers concluded that the incidence of immunogenicity or treatment-emergent ADAs in patients receiving chemotherapy and tbo-filgrastim was low across the 3 cancer populations tested, and that all positive samples had low-titer ADAs. None of the positive samples had cross-reactive ADAs to endogenous G-CSF, and none of the patients with positive ADA samples had clinically relevant immunogenicity-related symptoms during the study period.

Reference

1. Zou L, Buchner A, Field J, Barash S, Liu P. Immunogenicity assessment of tbo-filgrastim in cancer patients receiving chemotherapy. Presented at the American Society of Hematology 59th Annual Meeting and Exposition, December 10, 2017; Atlanta, Georgia. Abstract 2274. https://ash.confex.com/ash/2017/webprogram/Paper99985.html