Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study

Abstract

Background Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia. Patient and methods One hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21. Results Lipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was − 0.3 days (95% confidence interval, − 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 109/L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 109/L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease. Conclusions This study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile. Trial registration number ClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23

New insight into strategies used to develop long-acting G-CSF biologics for neutropenia therapy

“…Clinical trials of pegfilgrastim have been shown to have a favourable competence and safety profile for prophylactic usage in patients with cancer receiving chemotherapy and at risk of severe neutropenia and may be preferred by both physicians and patients over short-acting G-CSF due to enhanced adherence and a simple once-per-cycle subcutaneous injection ( 90 – 92 ). Lipegfilgrastim was found to be an effective option for reducing the duration of severe chemotherapy-induced neutropenia and preventing FN in older patients with aggressive B-cell NHL receiving MSC ( 36 ). Although the current studies published for lipegfilgrastim are still limited, there is an indication that it is a promising treatment for chemotherapy-induced neutropenia.…”

Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF)

“…This patient group benefits significantly from G-CSF prophylaxis, with a significant 5.7% reduction in the absolute risk of fatal complications after chemotherapy [27]. Dose intensity can be better maintained [29,74].…”