Biosimilar epoetin alfa (HX575) for the treatment of chemotherapy-induced anaemia: Development, approval and 10 years’ clinical experience

Abstract Background Epoetin and intravenous iron are used at St. Bartholomew's Hospital (Barts Health NHS Trust) for the treatment of patients with non-myeloid malignancy and chemotherapy-induced anemia. Modified American Society of Hematology/American Society of Clinical Oncology guidelines are used to guide epoetin use. This is combined with a systematic approach to iron supplementation based on iron status markers, including zinc protoporphyrin (ZPP). Using this approach, we have previously reported very high hemoglobin response rates of up to 92% with epoetin beta (Agrawal et al. Blood 2005; 106: Abs 588). Biosimilar versions of epoetin alfa are now approved in Europe to treat chemotherapy-induced anemia in patients with cancer. These agents offer potentially substantial cost savings to healthcare payers, and their greater affordability may increase patient access to treatments. We performed a pilot study of the effectiveness of biosimilar epoetin alfa (Sandoz, Germany) in our protocol for the management of chemotherapy-induced anemia in patients with hematological malignancies. Methods Patients with chronic lymphocytic leukemia (CLL), myeloma or lymphoma, receiving chemotherapy and with Hb<10 g/dL, were treated with biosimilar epoetin alfa (30,000 IU subcutaneously once weekly, increased to 60,000 IU at 4 weeks if no response [Hb increase<1 g/dL over baseline]). Minor and major responses to epoetin were defined as a Hb increase of 1–2 g/dL and >2 g/dL, respectively. Iron support was given in the form of intravenous (i.v.) iron sucrose 200 mg weekly if indicated based on iron status markers (serum ferritin, transferring saturation [TSAT], mean corpuscular Hb [MCH] and ZPP). Results Nineteen patients treated with biosimilar epoetin alfa were included in this analysis (9 with CLL, 7 with myeloma, 3 with lymphoma). Ages ranged from 25 to 84 years. 18 patients had a response to biosimilar epoetin alfa (95%); of these, 12 had a major response and 6 a minor response. Only one patient required an epoetin dose increase. Four patients were transfusion-dependent at baseline, 3 of whom became transfusion-independent on epoetin therapy. Seven of the 19 patients were ineligible for iron supplementation because of a serum ferritin >1000 μg/L. Of the remaining 12 patients, five (43%) received i.v. iron support based on their iron status markers at baseline and during epoetin therapy. In all five, the trigger for iron support was a raised ZPP in combination with a low/normal serum ferritin; TSAT was low in only 2/5and the MCH was normal in 5/5. All five patients achieved a response to epoetin. In contrast, five other patients who had a raised ZPP did not receive iron support because of markedly raised serum ferritin (>750 μg/L) with raised TSAT. Conclusions This pilot study indicates that biosimilar epoetin alfa is effective for the treatment of chemotherapy-induced anemia in patients with hematological malignancies. Although this is a small data set, response rates using biosimilar epoetin alfa in our epoetin/iron supplementation protocol (95%) are very high and similar to historical data using epoetin beta (92%). While ZPP appears to be a useful parameter to guide iron support in patients with hematological malignancies, it cannot be used in isolation and must be correlated with serum ferritin. Appropriate use of iron support, based on assessment of readily available laboratory parameters, may increase response rates to epoetin therapy. Disclosures: Agrawal: Sandoz Biopharmaceuticals: Consultancy, Honoraria, Research Funding. Turner:Sandoz Biopharmaceuticals: Employment.

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SP55824-MONTH SAFETY OUTCOMES OF BIOSIMILAR EPOETIN ALFA IN THE EUROPEAN MONITOR-CKD5 PHARMACOEPIDEMIOLOGICAL STUDY OF ANAEMIA IN HAEMODIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfw174.13 ◽

2016 ◽

Vol 31 (suppl_1) ◽

pp. i278-i278

Author(s):

David Goldsmith ◽

Johannes Mann ◽

Frank Dellanna ◽

Gerard London ◽

Christian Combe ◽

...

Keyword(s):

Epoetin Alfa ◽

Pharmacoepidemiological Study ◽

Safety Outcomes ◽

Biosimilar Epoetin Alfa

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Management of anaemia in oncohaematological patients treated with biosimilar epoetin alfa: results of an Italian observational, retrospective study

Therapeutic Advances in Medical Oncology ◽

10.1177/1758834016670554 ◽

2016 ◽

Vol 9 (1) ◽

pp. 22-32 ◽

Cited By ~ 6

Author(s):

Giovanni Rosti ◽

Mario Petrini ◽

Alberto Bosi ◽

Piero Galieni ◽

Daniele Bernardi ◽

...

Keyword(s):

Solid Tumour ◽

Solid Tumours ◽

Routine Practice ◽

Blood Transfusions ◽

Haematological Malignancies ◽

The European Union ◽

Epoetin Alfa ◽

Symptomatic Anaemia ◽

Biosimilar Epoetin Alfa

Background: Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice. Methods: The ANEMONE study was a national, longitudinal, retrospective, multicentre observational study. Patients had to be 18 years or older, with a solid tumour or non-Hodgkin’s lymphoma, Hodgkin’s disease or multiple myeloma, receiving chemotherapy, and treated with Binocrit® to manage chemotherapy-induced anaemia. The primary outcomes were the proportion of patients with a Hb increase ⩾1 g/dl during the first 4 weeks and with a Hb increase ⩾2 g/dl during the first 12 weeks. Results: A total of 245 patients were enrolled and 215 patients were evaluable for statistical analysis. In the first 4 weeks, 49.3% of patients showed an increase in Hb of ⩾1 g/dl: 45.5% in patients with solid tumours and 52.1% in patients with haematological malignancies. In the first 12 weeks, 51.6% of patients showed an increase in Hb of ⩾2 g/dl (48.4% solid tumours, 54.2% haematological diseases). Treatment with Binocrit® was well tolerated. Conclusions: These results confirm the effectiveness and safety of Binocrit® for chemotherapy-induced anaemia in routine practice in patients with solid tumours, lymphoma and myeloma.

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Management of Chemotherapy‐induced Anemia (CIA) with Biosimilar Epoetin Alfa (Binocrit®) in Patients with Multiple Myeloma (MM): An Interim Analysis of an Ongoing French National Observational Study (The OncoBOS study)

Blood ◽

10.1182/blood.v124.21.4001.4001 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4001-4001 ◽

Cited By ~ 1

Author(s):

Irina Voronina ◽

Mario Ojeda-Urib ◽

Charles Dauriac ◽

Laurent Voillat ◽

Camille Aubron-Olivier ◽

...

Keyword(s):

Observational Study ◽

Board Of Directors ◽

Treatment Period ◽

Iron Status ◽

Routine Practice ◽

Epoetin Alfa ◽

Advisory Committees ◽

Time Points ◽

The Mean ◽

Biosimilar Epoetin Alfa

Abstract Background: OncoBOS is a national, prospective, non-interventional, longitudinal, observational study describing biosimilar epoetin alfa (Binocrit®) use in routine practice in France in patients receiving chemotherapy treatment (CT) for solid tumors, lymphoma or myeloma. This sub-analysis focuses on the management of CIA in patients with MM. Patients and methods: Patients ≥18 years with MM, CIA and eligible for treatment with Binocrit® were included in this analysis. Patients characteristics, data on CIA and its management and predominant factors considered by the physician in prescribing Binocrit® were recorded at baseline, 3-4 weeks and 12 (± 1) weeks later. Hemoglobin (Hb) outcomes assessed included the proportion of patients achieving a Hb increase ≥1 and ≥2 g/dL, and the mean Hb change from baseline. Results: 99 patients with MM (mean age 71.1 years) from 20 sites were recruited from September 2011 to April 2014. 54.5% of subjects were male. Mean and median baseline Hb levels were 9.4 g/dL and 10 g/dL, respectively. The mean increase in Hb level was 1.1 g/dL after 1 month and 2.2 g/dL after 3 months (p<0.001 vs baseline) of Binocrit® treatment. A Hb increase ≥1 g/dL was achieved by 57.6% of patients at week 3-4 and 78.0% at week 12; a Hb increase ≥2 g/dL was achieved by 22.2% and 60.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit® once weekly. Four of the 99 patients (4.0%) required a dose increase; 3 of these patients had their dose doubled during the treatment period. Transfusion rates remained stable at 12.1% and 9.6% at week 3-4 and week 12, respectively. Oral and intravenous (IV) iron supplementation rates were low: oral iron was received by 1.0% and 2.2% of patients at week 3-4 and week 12, respectively; 1.0% and 1.1% of patients received IV supplementation at the same time points. Of note, these low rates could be explained by the fact that iron status (serum ferritin and transferrin saturation coefficient) was assessed in only 32.3% of subjects at baseline. Physicians considered quality of life (59.6%), fatigue (20.2%) and avoidance of blood transfusion (13.1%) as predominant factors in the rationale for anemia management and treatment. Over the treatment period, one treatment-related adverse reaction was recorded, which was not considered serious. Conclusion: This sub-analysis indicates that Binocrit®, used in routine practice, is effective and well tolerated for the treatment of CIA in patients with MM receiving CT. Disclosures Voronina: Sandoz: Investigator Other. Ojeda-Urib:Sandoz: Honoraria. Dauriac:Sandoz: Investigator Other. Voillat:Sandoz: Investigator Other. Aubron-Olivier:Sandoz: Employment. Fernet:Sandoz: Employment. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fitoussi:Sandoz: Honoraria.

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