Safety of Biosimilar Filgrastim in Patients with Haematological Malignancies Undergoing Neutropenia-Inducing Chemotherapy: A Subanalysis of the Next Study

Introduction

Febrile neutropenia (FN) is a major risk factor for infection-related morbidity/mortality as well as a dose-limiting toxicity in patients (pts) undergoing chemotherapy (CT). Biosimilar filgrastim (Nivestim^™, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. The NEXT (Nivestim^™ safety profile in patiEnts treated with cytotoXic CT in real-life clinical pracTice) study aimed to assess the safety of biosimilar filgrastim in pts undergoing CT for malignancies.

Methods

The NEXT study was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Adult pts (n=2114) undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as prophylaxis, or as curative treatment, were included. Data collected included pt characteristics, biosimilar filgrastim treatment-related data and treatment emergent AEs, including FN. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT. Here we present data for pts with haematological malignancies.

Results

Of the pts analysed, 525 had haematological malignancies (chronic lymphoid leukaemia [CLL]/acute lymphoid leukaemia [ALL]: 70; lymphoma: 408; myeloma: 47). Overall, the mean age ± standard deviation (SD) of pts with haematological malignancies was 64.8 ± 15.4 years (64.4% male). At inclusion, 88.0% of pts had no prior FN (CLL/ALL: 88.6%; lymphoma: 89.2%; myeloma: 76.6%); 31.1% had prior CT (CLL/ALL: 32.9%; lymphoma: 27.5%; myeloma: 59.6%) and 27.1% had prior G-CSF therapy (CLL/ALL: 21.4%; lymphoma: 26.7%; myeloma: 38.3%). Of the pts prescribed a prior G-CSF therapy, 39.2% received biosimilar filgrastim. The majority of pts (98.9%) received biosimilar filgrastim prophylactically (CLL/ALL: 100.0%; lymphoma: 98.8%; myeloma: 97.9%).

Of the group receiving biosimilar filgrastim with curative intent, the median time to initiation of biosimilar filgrastim therapy was 14.0 days after the start of the last CT cycle (lymphoma: 14.0 days; myeloma: 14.0 days); mean treatment duration ± SD was 4.8 ± 1.6 days (lymphoma: 5.2 ± 1.5 days; myeloma: 3.0 ± 0.0 days). In this group, 50.0% of pts received a dose of 30 MIU (lymphoma: 40.0%; myeloma: 100.0%) and biosimilar filgrastim was administered subcutaneously in all pts.

In the prophylactic biosimilar filgrastim group, the median time to initiation of biosimilar filgrastim was 6 days after start of the last CT cycle (CLL/ALL: 6.0 days; lymphoma: 6.0 days; myeloma: 6.5 days); mean treatment duration ± SD was 6.7 ± 4.6 days (CLL/ALL: 7.5 ± 7.0 days; lymphoma: 6.6 ± 4.0 days; myeloma: 5.9 ± 4.5 days). In this group, 70.9% of pts received a dose of 30 MIU (CLL/ALL: 57.1%; lymphoma: 72.5%; myeloma: 78.3%) and biosimilar filgrastim was administered subcutaneously in all pts. Anti-infective prophylaxis was reported in 51.2% of pts (CLL/ALL: 88.6%; lymphoma: 42.9%; myeloma: 67.4%). In the prophylactic group, 7.5% (95% confidence interval [CI] 5.5, 10.1) experienced FN (CLL/ALL: 7.1% [2.7, 16.0]; lymphoma: 7.1% [4.9, 10.1]; myeloma: 10.9% [4.3, 23.5]).

Of the pts with haematological malignancies, 18.6% experienced ≥1 AE (CLL/ALL: 8.6%; lymphoma: 21.5%; myeloma: 8.5%). The most common AEs (>5.0% of pts) were bone/muscular disorders (total: 13.7% [CLL/ALL: 7.1%, lymphoma: 16.0% myeloma: 4.3%]) and muscle pain (total: 13.4% [CLL/ALL: 7.1%, lymphoma: 15.5% myeloma: 4.3%]). In this analysis, 7.5% of pts were hospitalised for FN and/or infection (CLL/ALL: 7.1%; lymphoma: 7.1%; myeloma: 10.9%). The mean duration of hospitalisation ± SD for FN and/or infection after the first CT cycle was 11.3 ± 16.2 days (CLL/ALL: 10.5 ± 6.4 days; lymphoma: 11.4 ± 17.4 days; myeloma: 0.0 ± 0.0 days), 3.4% of pts had a CT dose reduction (CLL/ALL: 2.1%; lymphoma: 2.8%; myeloma: 2.3%) and 7.7% of pts (CLL/ALL: 15.7%; lymphoma: 5.9%; myeloma: 11.4%) had a delay in administration of CT due to FN and/or infection.

Conclusion

Biosimilar filgrastim was effective and well-tolerated in pts undergoing CT for haematological malignancies and is an alternative therapeutic option for pts with CT-induced neutropenia.