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Cost Effectiveness of Pegfilgrastim Versus Filgrastim After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Lymphoma and Myeloma

An Economic Evaluation of the PALM Trial

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Abstract

Background

Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet.

Objective

We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100 ± 10 days from transplant.

Methods

The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital’s point of view and are expressed in 2009 euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann–Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5 × 109/L and temperature ≥38 °C), duration of neutropenia (ANC <1.0 × 109/L and ANC <0.5 × 109/L), duration of thrombopenia (platelets <50 × 109/L and <20 × 109/L), and days with a temperature ≥38 °C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method.

Results

151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n = 74) was €25,024 (SD 9,945). That in the filgrastim arm (n = 76) was €28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0 × 109/L) avoided, days of thrombopenia (platelets <20 × 109/L) avoided, and days with temperature ≥38 °C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5 × 109/L avoided and the number of days with platelets <50.0 × 109/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC <1.0 × 109/L), 59 % for thrombopenia (platelets <20 × 109/L), 86 % for temperature ≥38 °C, 32 % for neutropenia (ANC <0.5 × 109/L), and 43 % for thrombopenia (platelets <50 × 109/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5 × 109/L) is 5 %.

Conclusion

This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.

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Acknowledgment

The authors are grateful to the coordinating staff, physicians, clinical research assistants and nursing staff involved in this study as well as to the chief financial officers and pharmacists of participating centres. The authors also gratefully acknowledge Magali Hureau, Gérard de Pouvourville and Patrick Sylvestre Baron for feedback on a preliminary version of this paper. The authors thank Amgen France for its support in conducting this study. The authors would like to thank the referees for their insightful comments and suggestions. Rob Stepney, medical writer, Charlbury, UK, assisted with the final editing of the manuscript.

Source of financial support:

The study received research support from AMGEN Inc., Thousand Oaks, CA, USA. AMGEN had no involvement in the design, in the data management, in the analysis, or in the interpretation and reporting of this study.

Authors’ contributions

LP, AL, DP, CS designed the study, acquired and interpreted the clinical and cost data, undertook the statistical analysis, and prepared the manuscript. PQ, AST, BF, PB, PM, JOB, SL, FJ, DE participated in clinical data acquisition and analysis. CS, CP participated in the statistical analysis. CS is guarantor for the overall content of this manuscript.

Authorisation of the Commission Nationale de l’Informatique et des Libertés (CNIL):

1257249.

Unique Protocol ID:

PALM.

Secondary IDs:

ET2007–113.

Trial registration number:

NCT00794261.

Author information

Authors and Affiliations

  1. Department Cancer and Environment, Cancer Centre Léon Bérard, University of Lyon, GATE Lyon-St Etienne, UMR-CNRS 5824, 28 rue Laënnec, 69373, Lyon Cedex 08, France

    Lionel Perrier

  2. Biostatistics Unit, Cancer Centre Léon Bérard, Lyon, France

    Anne Lefranc & David Pérol

  3. Haematology Unit, University Hospital Saint Eloi, Montpellier, France

    Philippe Quittet

  4. University Hospital, INSERM U892, Angers, France

    Aline Schmidt-Tanguy

  5. ERIC EA3083, University of Lyon, Lyon, France

    Carole Siani

  6. Laboratory of Actuarial and Financial Sciences SAF, EA2429, University Claude Bernard Lyon 1, Lyon, France

    Christian de Peretti

  7. Pharmacy, Cancer Centre Léon Bérard, Lyon, France

    Bertrand Favier

  8. Haematology Unit, Cancer Centre Léon Bérard, Lyon, France

    Pierre Biron & Catherine Sebban

  9. University Hospital, Nantes, France

    Philippe Moreau

  10. Haematology Department, University Hospital, Clermont-Ferrand, France

    Jacques Olivier Bay

  11. University Hospital Bretonneau, Tours, France

    Séverine Lissandre

  12. Haematology Department, Cancer Centre Henri Becquerel, Rouen, France

    Fabrice Jardin

  13. Haematology Unit, University Hospital Lyon sud, Pierre Bénite, France

    Daniel Espinouse

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  1. Lionel Perrier
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  15. Catherine Sebban
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Corresponding author

Correspondence to Lionel Perrier.

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Perrier, L., Lefranc, A., Pérol, D. et al. Cost Effectiveness of Pegfilgrastim Versus Filgrastim After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Lymphoma and Myeloma. Appl Health Econ Health Policy 11, 129–138 (2013). https://doi.org/10.1007/s40258-013-0011-7

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