ASCO has issued a clinical practice guideline update on use of hematopoietic colony-stimulating factors, as reported in the Journal of Clinical Oncology by Thomas J. Smith, MD, FACP, FASCO, FAAHMP, and colleagues.¹ This update to the ASCO 2006 guideline was based on a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014 by an ASCO update committee. The committee was co-chaired by Dr. Smith, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, and James O. ­Armitage, MD, FASCO, of the University of Nebraska Medical Center.

Changes to prior recommendations include the addition of tbo-filgrastim and the biosimilar filgrastim-sndz (Zarxio), moderation of the recommendation regarding routine use of colony-stimulating factors in older patients with diffuse aggressive lymphoma, and the addition of recommendations against routine dose-dense chemotherapy in lymphoma and in favor of high dose-intensity chemotherapy in urothelial cancer. The updated guideline does not address recommendations on the use of colony-stimulating factors in acute myeloid leukemia or myelodysplastic syndromes in adults.

A summary of the updated recommendations is reproduced below. Type of recommendation, evidence quality, and strength of recommendation are shown in parentheses.

Recommendations

Primary prophylaxis with a colony-stimulating factor starting with the first cycle and continuing through subsequent cycles of chemotherapy is recommended in patients with an approximately 20% or higher risk for febrile neutropenia based on patient-, disease-, and treatment-related factors. Primary colony-stimulating factor prophylaxis should also be administered in patients receiving dose-dense chemotherapy when considered appropriate. Consideration should be given to alternative, equally effective, and safe chemotherapy regimens not requiring colony-stimulating factor support when available. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Secondary prophylaxis with a colony-stimulating factor is recommended for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose or treatment delay may compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or delay may be a reasonable alternative. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Colony-stimulating factors should not be routinely used for patients with neutropenia who are afebrile. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Colony-stimulating factors should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia. However, colony-stimulating factors should be considered in patients with fever and neutropenia who are at high risk for infection-associated complications or who have prognostic factors predictive of poor clinical outcomes. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Dose-dense regimens with colony-stimulating factor support should only be used if supported by convincing efficacy data or within an appropriately designed clinical trial. Efficacy data support the use of dose-dense chemotherapy in the adjuvant treatment of high-risk breast cancer and the use of high-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin in urothelial cancer. There are limited and conflicting data on the value of dose-dense regimens with colony-stimulating factor support in non-Hodgkin lymphoma, and it cannot routinely be recommended at this time. (type = evidence based, benefits outweigh harms; evidence quality = high for breast cancer and lymphoma, intermediate for urothelial cancer; strength of recommendation = strong for breast cancer and lymphoma, moderate for urothelial cancer)

Colony-stimulating factors may be used alone, after chemotherapy, or in combination with plerixafor ­(Mozobil) to mobilize peripheral-blood progenitor cells. Choice of mobilization strategy depends in part on the type of cancer and the type of transplantation. (type = evidence based, benefits outweigh harms; evidence quality = strong; strength of recommendation = high)

Colony-stimulating factors should be administered after autologous stem cell transplantation to reduce the duration of severe neutropenia. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Colony-stimulating factors may be administered after allogeneic stem cell transplantation to reduce the duration of severe neutropenia. (type = evidence based; evidence quality = low; strength of recommendation = weak)

Prophylactic colony-stimulating factors for patients aged ≥ 65 years with diffuse aggressive lymphoma treated with curative chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab [Rituxan]) should be considered, particularly in the presence of comorbidities. (type = evidence based, benefits outweigh harms; evidence quality = intermediate; strength of recommendation = moderate)

The use of colony-stimulating factors in pediatric patients will almost always be guided by clinical protocols. As in adults, the use of colony-stimulating factors is reasonable as primary prophylaxis for pediatric patients with a high likelihood of febrile neutropenia. Similarly, the use of colony-stimulating factors for secondary prophylaxis or for therapy should be limited to high-risk patients. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

For pediatric indications in which dose-intense chemotherapy is known to have a survival benefit, such as Ewing sarcoma, colony-stimulating factors should be used to enable the administration of these regimens. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Colony-stimulating factors should not be used in pediatric patients with nonrelapsed acute lymphoblastic leukemia or nonrelapsed acute myeloid leukemia who do not have an infection. (type = informal consensus; evidence quality = intermediate; strength of recommendation = moderate)

Pegfilgrastim (Neulasta), filgrastim (Neupogen), tbo-filgrastim, and filgrastim-sndz (and other biosimilars, as they become available) can be used for the prevention of treatment-related febrile neutropenia. The choice of agent depends on convenience, cost, and clinical situation. There have been no additional data comparing granulocyte colony-stimulating factors and granulocyte-macrophage colony-stimulating factors since the 2006 update; therefore, there is no change in the recommendation regarding their therapeutic equivalency. (type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong)

Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death resulting from injury to other organs, include the prompt administration of colony-stimulating factors or pegylated granulocyte colony-stimulating factors. (type = formal consensus [by others], benefits outweigh harms; evidence quality = intermediate; strength of recommendation = moderate)  ■

Disclosure: Dr. Smith owns stock in United Healthcare. Dr. Armitage has a leadership position with Tesaro Bio and a consulting or advisory role with GlaxoSmithKline, Roche, Spectrum Pharmaceuticals, Ziopharm Oncology, Conatus IDMC, and Celgene. For full disclosures of the other authors, visit jco.ascopubs.org.

Reference

1. 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 33:3199-3212, 2015.