PF353 PATIENTS WITH SEVERE CHRONIC NEUTROPENIA SUBTYPES TREATED WITH BIOSIMILAR FILGRASTIM: A STUDY BY THE EUROPEAN BRANCH OF THE SEVERE CHRONIC NEUTROPENIA INTERNATIONAL REGISTRY
Authors: Zeidler C. , Mellor‐Heineke S. , Nakov R. , Natek M. , Mathieson N. , Gattu S. 
Published: June 2019

Background:

Severe chronic neutropenia (SCN) is a group of very rare blood disorders, characterised by low levels of neutrophils (<500/μl) lasting for extended periods of time, while other blood‐cell counts remain close to or within normal range. Since the introduction of granulocyte colony‐stimulating factor (G‐CSF) therapy in 1987, the prognosis and quality of life of patients with congenital neutropenia has vastly improved. The Severe Chronic Neutropenia International Registry (SCNIR), established in 1994, has gathered data on over 2,000 patients with SCN worldwide in order to monitor the clinical course, treatment and disease outcomes of patients with these rare diseases.

Aims:

This report by the European Branch of the SCNIR aims to compare results of patients with SCN treated with G‐CSF products (reference filgrastim, pegfilgrastim, lenograstim) with those who received Sandoz biosimilar filgrastim (Zarzio® or Filgrastim Hexal®) from July 2011 to March 2018.

Methods:

Since 1994, the European Branch of the SCNIR has been establishing a network including 26 European countries, Israel, Russia and Turkey. Clinical data on the course of neutropenia is collected after written informed consent by the patient or their legally authorised representative; all consent forms have been standardised and accepted by all local ethics committees.

Results:

Between 2011 and 2018, 789 patients were enrolled in the European registry, 578 (73.3%) of which had received G‐CSF. Of all G‐CSF treated patients (median age stable at approximately 14 years), the most common neutropenia diagnosis was congenital (n = 377), then cyclic (n = 88), idiopathic (n = 62), autoimmune (n = 30) and other (n = 21). Median G‐CSF dose was 3.01 μg/kg/day.

Twenty‐one patients (median age 14.5 years; range 0.7–48.2 years) had received Sandoz biosimilar filgrastim (Zarzio®, n = 15; Filgrastim Hexal®, n = 6). Of the 21 patients, 16 had changed medication from other G‐CSF products. The most common diagnosis of neutropenia among these patients was congenital (n = 12) followed by cyclic (n = 6), idiopathic, autoimmune and other (n = 1 each). Median treatment duration was 1.5 (range, 0.1–4.4) years and median dose was 2.27 (range, 0.25–40) μg/kg/day. Absolute neutrophil counts (ANCs) during treatment indicated that all patients responded well to Sandoz biosimilar filgrastim. ANCs remained stable in the 16 patients who changed medication.

Of the 578 patients who received G‐CSF, 50 have developed leukaemia secondary to SCN. Only one of these patients received Sandoz biosimilar filgrastim (Filgrastim Hexal® from March 2009 to November 2011); this patient suffered from congenital neutropenia and underwent successful stem cell transplant. So far, there have been no reports of osteoporosis, severe splenomegaly, splenic rupture, severe side effects or immunogenicity in any patient that received Sandoz biosimilar filgrastim.

Summary/Conclusion:

Efforts to register all patients with SCN within the co‐operating countries are ongoing, with the aim of estimating the incidence and prevalence of these rare disorders and the incidence of severe secondary events like leukaemia. G‐CSF remains the treatment of choice for patients with congenital neutropenia to maintain their ANC above 1,000/μL, which is required for the prevention of severe infections. With Sandoz biosimilar filgrastim, no new safety signals were observed and only one patient has developed leukaemia secondary to SCN during the observation period. In general, secondary leukaemia in congenital neutropenia patients is related to the underlying genetic disorder.