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

Hartmut Link,S Mahlmann,U M Martens,P Bias,M Zaiss,R Depenbusch,A Köhler,M Engelhardt,A Lammerich,G Illerhaus,A Salar,A Buchner

doi:10.1007/s00520-020-05711-7

Abstract

BackgroundLipegfilgrastim 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 methodsOne hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21.ResultsLipegfilgrastim 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.ConclusionsThis 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 numberClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23

Highlights

Patients with non-Hodgkin lymphoma (NHL) receiving chemotherapy, such as R-CHOP, are at high risk of developing clinically significant neutropenia [1,2,3], which can lead to dose reductions, cycle delays, or even treatment discontinuation
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
Lipegfilgrastim (Lonquex®; Teva B.V., Haarlem, Netherlands) is a long-acting granulocyte colony–stimulating factors (G-CSFs) indicated for reduction of the duration of neutropenia and the incidence of febrile neutropenia (FN) in adult patients receiving cytotoxic chemotherapy [12]

Summary

Introduction

Patients with non-Hodgkin lymphoma (NHL) receiving chemotherapy, such as R-CHOP, are at high risk of developing clinically significant neutropenia [1,2,3], which can lead to dose reductions, cycle delays, or even treatment discontinuation. Lipegfilgrastim has been shown to induce a longer-lasting increase in ANC than an equivalent dose of the conventionally glycopegalated long-acting G-CSF, pegfilgrastim (Neulasta®; Amgen Inc., Thousand Oaks, CA, USA) [15] This may reflect the higher cumulative exposure and slower clearance of lipegfilgrastim compared with pegfilgrastim [15]. Lipegfilgrastim, administered once per chemotherapy cycle, has been shown to be non-inferior to pegfilgrastim with respect to duration of severe neutropenia (DSN, defined as the number of days with grade 4 neutropenia [ANC < 0.5 × 109/ L]) in breast cancer patients [16]. 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 chemotherapyinduced neutropenia.

Methods

Results

Conclusion