Prophylaxis with Myeloid Growth Factors

The prophylactic use of myeloid growth factors decreases the risk of neutropenia, febrile neutropenia, and rates of infection.1 Prophylaxis also improves the relative chemotherapy dose intensity received. Results of some meta-analyses suggest that myeloid growth factor use may also decrease infection-related mortality and death during chemotherapy.

The NCCN and the ASCO guidelines for the use of growth factors recommend that all patients receiving high-risk chemotherapy should receive neutropenia prophylaxis with a granulocyte-colony–stimulating factor (G-CSF) or, for patients undergoing induction for hematopoietic cell transplantation for acute myeloid leukemia, granulocyte-macrophage colony–stimulating factor (GM-CSF).1,5 The NCCN also recommends that G-CSF be considered for patients receiving intermediate-risk chemotherapy, particularly if 1 or more patient-associated risk factors are present. Patients receiving low-risk chemotherapy should not be treated with G-CSF.

Currently, the US Food and Drug Administration (FDA)–approved G-CSF products include filgrastim and its biosimilars or recombinants filgrastim-sndz, tbo-filgrastim, and filgrastim-aafi, as well as the longer half-life products pegfilgrastim and its biosimilar pegfilgrastim-jmdb. The NCCN recommends either filgrastim-sndz or tbo-filgrastim as frequently as it recommends the innovator product, but notes that there are insufficient data for NCCN to include the newer biosimilars, such as filgrastim-aafi and pegfilgrastim-jmbd in their recommendations.1 The only FDA-approved GM-CSF is sargramostim. The selection of a specific G-CSF product will be based on treatment plan and schedule, cost, and convenience.2 Biosimilars typically cost less than their associated reference products.1

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Filgrastim and its biosimilars are dosed daily through post-nadir ANC recovery, beginning the day of, the day after, or up to 3 to 4 days after chemotherapy.1 In contrast, pegfilgrastim and its biosimilar have longer half-lives, allowing them to be administered as a single dose per chemotherapy cycle. Although pegfilgrastim is recommended to be dosed the day after or up to 4 days following chemotherapy, some institutions administer it the day of chemotherapy to accommodate patient travel concerns. The FDA recently approved a delivery device for pegfilgrastim that administers the full dose the day after chemotherapy, thereby allowing day-after administration of pegfilgrastim for patients who cannot return to clinic.

Treatment of Neutropenia and Febrile Neutropenia

The benefits of treating neutropenia or febrile neutropenia with myeloid growth factors are less clear than the benefits of prophylactic therapy. A meta-analysis of 1518 patients across 13 trials demonstrated that G-CSF treatment of febrile neutropenia resulted in a shorter length of hospitalization and shorter time to neutrophil recovery, but did not improve overall survival. Based on the current data, the NCCN recommends that patients already receiving G-CSFs who then develop febrile neutropenia should continue to receive the same G-CSF product. Clinicians should consider risk factors for infection and clinical outcomes when determining if patients who are not already receiving G-CSF should be receive G-CSF as an adjunct to antibiotic treatment for febrile neutropenia.

Patients who develop febrile neutropenia, with no other known reason for fever, should be treated for infection with empirical antibiotics.2 Patients with a high risk of complications should receive treatment as inpatients, whereas clinically stable patients with a low risk for complications may be candidates for outpatient treatment.

References

  1. Crawford J, Becker PS, Alwan L, et al. National Comprehensive Cancer Network clinical practice guidelines in oncology: Myeloid growth factors. Version 2.2018. www.nccn.org.   Updated August 3, 2018. Accessed September 6, 2018.
  2. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. J Clin Oncol. 2018;36(14):1443-1453.
  3. Lalami Y, Klastersky J. Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: an overview about well-established and recently emerging clinical data. Crit Rev Oncol Hematol. 2017;120:163-179.
  4. Truong J, Lee EK, Trudeau ME, Chan KKW. Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):608-618.
  5. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33(28):3199-3212.
  6. What you need to know: neutropenia and risk for infection. National Center for Chronic Disease Prevention and Health Promotion, Division of Cancer Prevention and Control. https://www.cdc.gov/cancer/preventinfections/pdf/neutropenia.pdf. Accessed September 5, 2018.