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Association Between Granulocyte Colony-Stimulating Factor (G-CSF) Use and Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Among Elderly Patients with Breast, Lung, or Prostate Cancer

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Abstract

Introduction

Patients diagnosed with cancer have an increased risk both for myelodysplastic syndromes (MDS) and for acute myeloid leukemia (AML) following treatment.

Methods

Using SEER-Medicare data, we selected patients aged 66 years and older who completed systemic therapy between 2002 and 2014 for breast (stage I–III), lung (stage I–III), or prostate (stage I–IV) cancer. For each cancer, we estimated the risk of a composite endpoint of MDS or AML in patients receiving granulocyte colony-stimulating factor (G-CSF) vs. not.

Results

The 10-year cumulative risk difference (granulocyte colony-stimulating factor [G-CSF] − no G-CSF) for MDS-AML was 0.45% (95% CI 0.13–0.77%) in breast cancer and 0.39% (95% CI 0.15–0.62%) in lung cancer. G-CSF use was associated with a hazard ratio of 1.60 (95% CI 1.07–2.40) in breast cancer and 1.50 (95% CI 0.99–2.29) in lung cancer. Filgrastim use was associated with a hazard ratio of 1.01 (95% CI 1.00–1.03) per administration in breast cancer and 1.02 (95% CI 0.99–1.05) per administration in lung cancer. Pegfilgrastim was associated with a hazard ratio of 1.08 (95% CI 1.01–1.15) per administration in breast cancer and 1.12 (95% CI 1.00–1.25) per administration in lung cancer. Analyses in prostate cancer were limited because of the low number of events.

Conclusions

The use of G-CSF in patients diagnosed with breast and lung cancer is associated with an increased risk of MDS-AML. However, the MDS-AML absolute risk difference is very low.

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Acknowledgements

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database.

Funding

Outcomes Insights, Inc was funded by Amgen to conduct this study. Amgen also paid the journal’s Rapid Service fees. Prior to conducting the research, Outcomes Insights, Inc. was permitted to publish the results of this study by Amgen, Inc., which is a requirement in the data use agreement with the National Cancer Institute.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

All authors contributed to the conception, study design, and protocol development. Mark Danese conducted the data analyses. Mark Danese and Jennifer Schenfeld were responsible for creating the initial draft. All authors were involved in revising the initial draft and approving the final version. All authors agree to be accountable for the integrity of the research.

Disclosures

At the time this research was conducted Jennifer Schenfeld, Jaime Shaw, Prasad Gawade, Akhila Balasubramanian, Michael Kelsh, and Rohini K. Hernandez were Amgen employees and Amgen stockholders. Gary Lyman served as a Principal Investigator on an institutional grant from Amgen, Inc. and received speaking or consulting fees from G1 Therapeutics, Partners Healthcare, BeyondSpring, Squibb (institutional), Sandoz, Merck, Jazz, Kallyope, and TEVA. Mark Danese was an owner of Outcomes Insights, Inc. Outcomes Insights, Inc. received research funding to conduct this study, including funding for developing the manuscript. Outcomes Insights, Inc. has also received consulting fees from Amgen related to methods for observational research. Outcomes Insights, Inc. provided research and consulting services in oncology to Bristol Myers Squibb, Seattle Genetics, Boston Scientific, Mirati, EMD Serono, and Taiho.

Compliance with Ethics Guidelines

The study protocol was reviewed by Advarra and received an exemption determination on 24 May 2019. The authors received permission to access and use the USRDS data from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Data Availability

The data sets generated for the current study are not publicly available to ensure patient privacy, as required by the data use agreement with the National Cancer Institute

Author information

Authors and Affiliations

  1. Outcomes Insights, Inc., 30200 Agoura Road, Suite 230, Agoura Hills, CA, 91301, USA

    Mark D. Danese

  2. Center for Observational Research, Amgen, Thousand Oaks, CA, USA

    Jennifer Schenfeld, Jaime Shaw, Akhila Balasubramanian, Michael Kelsh & Rohini K. Hernandez

  3. Vertex Pharmaceuticals, Boston, MA, USA

    Prasad Gawade

  4. Hutchinson Institute for Cancer Outcomes Research (HICOR), Fred Hutchinson, Seattle, WA, USA

    Gary Lyman

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  1. Mark D. Danese
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Correspondence to Mark D. Danese.

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Danese, M.D., Schenfeld, J., Shaw, J. et al. Association Between Granulocyte Colony-Stimulating Factor (G-CSF) Use and Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Among Elderly Patients with Breast, Lung, or Prostate Cancer. Adv Ther 39, 2778–2795 (2022). https://doi.org/10.1007/s12325-022-02141-1

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  • DOI: https://doi.org/10.1007/s12325-022-02141-1

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