Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study

Aim. To assess effectiveness and safety of Extimia® BIOCAD (INN: empegfilgrastim) used to decrease the rate and duration of neutropenia, the rate of febrile neutropenia and infections that manifest in febrile neutropenia in patients with lymphoproliferative diseases who receive myelosuppressive therapy.

Materials and methods. The paper presents the results of the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study of effectiveness and safety of Extimia® BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases who receive cytotoxic therapy. The second stage of the interim analysis describes patient characteristics, therapy used in 221 patients with morphologically confirmed lymphoma who received one or more cycles of chemotherapy as part of LEGERITY study. The endpoints of interest included the rate of Grade 3/4 neutropenia in patients, after the first cycle of any therapy line; the rate of febrile neutropenia; the rate of Grade 3/4 infectious complications; the rate of antibacterial therapy prescriptions; and the assessment of the relative dose-intensity of received chemotherapy. Additionally, the incidence rate of all adverse drug reactions (ADRs) was assessed in patients who received at least one dose of the study drug; the incidence rate of all serious ADRs was assessed in patients who received at least one dose of the study drug; the incidence rate of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 3/4 ADRs – in patients who received at least one dose of the study drug; the rate of study drug discontinuations due to ADRs was also assessed.

Results. As of the second interim analysis, LEGERITY included 221 patients with various indolent and aggressive lymphomas. Median age of the patients was 53 years (19–82). A group of older patients (over 60 years of age) accounted for 34% of the study population. Patients received ≤1 injection of Extimia per chemotherapy cycle. Grade 3/4 neutropenia was registered in 6.7% (n=14) patients. Overall, all-grade neutropenia was reported in 21.4% (n=44) patients. Febrile neutropenia was reported in 2.9% cases. Severe infections and the use of antimicrobials were reported in no patients throughout the CT period and after each cycle of therapy. Most commonly reported adverse reactions included mild-to-moderate ossalgias (6.8%) and myalgias, back pain, and arthralgias (3.2%), that did not require pharmaceutical therapy. One (0.5%) patient had a severe adverse drug reaction – a CTCAE 5.0 Grade 4 hypotension episode.

Conclusion. Interim analysis results support high effectiveness and safety of the Russian original pegylated granulocyte colony-stimulating factor of empegfilgrastim (Extimia®) in patients both with indolent and aggressive lymphomas. Real world evidence demonstrates a favourable safety and tolerability profile of empegfilgrastim in all age groups, including in the aging population. As of the moment of the interim analysis publication, the study is ongoing. Final conclusions on the safety and effectiveness of empegfilgrastim (Extimia®) are to be drawn upon the study completion.