1520 NCCN Ayman A. Saad, MD; Lee S. Schwartzberg, MD; Sepideh Shayani, PharmD; Mahsa Talbott, PharmD; Saroj Vadhan-Raj, MD; Sumithira Vasu, MBBS; Myeloid Growth Factors, Martha Wadleigh, MD; Peter Westervelt, MD, PhD; Jennifer L. Burns; and Lenora Pluchino, PhD Version 2.2017 Overview Clinical Practice Guidelines in Oncology Myeloid growth factors (MGFs) are a class of biolog- Jeffrey Crawford, MD; Pamela Sue Becker, MD, PhD; ic agents that regulate the proliferation, differentia- James O. Armitage, MD; Douglas W. Blayney, MD; tion, survival, and activation of cells in the myeloid Julio Chavez, MD; Peter Curtin, MD; Shira Dinner, MD; Thomas Fynan, MD; Ivana Gojo, MD; lineage. In patients with cancer receiving myelosup- Elizabeth A. Griffiths, MD; Shannon Hough, PharmD, BCOP; pressive chemotherapy, MGFs are primarily used to Dwight D. Kloth, PharmD, BCOP; David J. Kuter, MD, DPhil; reduce the incidence of neutropenia. Neutropenia is Gary H. Lyman, MD, MPH, FRCP; Mary Mably, RPh, BCOP; defined as an absolute neutrophil count (ANC) of Sudipto Mukherjee, MD, PhD, MPH; Shiven Patel, MD; <500 neutrophils/mcL or an ANC of <1,000 neu- Lia E. Perez, MD; Adam Poust, PharmD; trophils/mcL and a predicted decline ≤500 neutro- Raajit Rampal, MD, PhD; Vivek Roy, MD; Hope S. Rugo, MD; phils/mcL over the next 48 hours. Neutropenia can Abstract Please Note Myeloid growth factors (MGFs) are given as supportive care to The NCCN Clinical Practice Guidelines in Oncol- patients receiving myelosuppressive chemotherapy to reduce ogy (NCCN Guidelines®) are a statement of consensus the incidence of neutropenia. This selection from the NCCN of the authors regarding their views of currently accepted Guidelines for MGFs focuses on the evaluation of regimen- approaches to treatment. Any clinician seeking to apply and patient-specific risk factors for the development of febrile or consult the NCCN Guidelines® is expected to use in- neutropenia (FN), the prophylactic use of MGFs for the preven- tion of chemotherapy-induced FN, and assessing the risks and dependent medical judgment in the context of individual benefits of MGF use in clinical practice. clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Net- J Natl Compr Canc Netw 2017;15(12):1520–1541 ® ® doi: 10.6004/jnccn.2017.0175 work (NCCN ) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or NCCN Categories of Evidence and Consensus use in any way. The full NCCN Guidelines for Myeloid Category 1: Based upon high-level evidence, there is uni- Growth Factors are not printed in this issue of JNCCN form NCCN consensus that the intervention is appropriate. but can be accessed online at NCCN.org. Category 2A: Based upon lower-level evidence, there is © National Comprehensive Cancer Network, Inc. uniform NCCN consensus that the intervention is appro- 2017, All rights reserved. The NCCN Guidelines and the priate. illustrations herein may not be reproduced in any form Category 2B: Based upon lower-level evidence, there is without the express written permission of NCCN. NCCN consensus that the intervention is appropriate. Disclosures for the NCCN Myeloid Growth Factors Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is ap- At the beginning of each NCCN Guidelines panel meeting, panel propriate. members review all potential conflicts of interest. NCCN, in keep- ing with its commitment to public transparency, publishes these All recommendations are category 2A unless otherwise disclosures for panel members, staff, and NCCN itself. noted. IIndividual disclosures for the NCCN Myeloid Growth Factors Clinical trials: NCCN believes that the best management for Panel members can be found on page 1541. (The most recent any cancer patient is in a clinical trial. Participation in clinical version of these guidelines and accompanying disclosures are trials is especially encouraged. available on the NCCN Web site at NCCN.org.) These guidelines are also available on the Internet. For the latest update, visit NCCN.org. ©© JNCCN—JournalJNCCN—Journal ofof thethe NationalNational ComprehensiveComprehensive CancerCancer NetworkNetwork || VolumeVolume 1515 NumberNumber 1212 || DecemberDecember 20172017 1521 NCCN Guidelines® Journal of the National Comprehensive Cancer Network Myeloid Growth Factors progress to febrile neutropenia (FN; ≥38.3°C orally or literature on randomized clinical trials of chemo- ≥38.0°C duration over 1 hour), which is a major dose- therapy in patients with early-stage breast cancer limiting toxicity of chemotherapy that often requires and non-Hodgkin’s lymphoma (NHL) has shown prolonged hospitalization and broad-spectrum antibi- that the rates of myelosuppression and delivered otic use.1 Occurrences of severe neutropenia or FN can dose intensity are underreported.4 Due to indi- prompt dose reductions or treatment delays in subse- vidual patient risk factors, the rates of myelosup- quent chemotherapy cycles and compromise clinical pression with the same or similar regimens varied outcome. A review by Dale2 showed that approximately greatly, making it difficult to determine the actual 25% to 40% of treatment-naive patients develop FN risk for neutropenic complications associated with with common chemotherapy regimens. Development of common chemotherapy regimens.4 Treatment FN increases diagnostic and treatment costs and often dose intensity was reported with even less consis- leads to longer hospital stays. In addition, correlations tency, complicating interpretation of the reported have been reported between changes in neutrophil rates of toxicity or treatment efficacy. Thus, differ- counts and quality of life, as measured by physical func- ences in the reported rates of myelotoxicity may tioning, vitality, and mental health.3 be attributed to intrinsic variation in the patient The risk of FN is related to the treatment regimen population as well as differences in the delivered and delivered dose intensity. However, a survey of the dose intensities. Text cont. on page 1531. NCCN Myeloid Growth Factors Shiven Patel, MD† Huntsman Cancer Institute at the University of Utah Panel Members Lia E. Perez, MD‡ Moffitt Cancer Center *Jeffrey Crawford, MD/Chair†‡ Adam Poust, PharmD† Duke Cancer Institute University of Colorado Cancer Center *Pamela Sue Becker, MD, PhD/Vice Chair‡Þξ Raajit Rampal, MD, PhD‡Þ† Fred Hutchinson Cancer Research Center/ Memorial Sloan Kettering Cancer Center Seattle Cancer Care Alliance Vivek Roy, MD‡ James O. Armitage, MD†ξ‡ Mayo Clinic Cancer Center Fred & Pamela Buffett Cancer Center Hope S. Rugo, MD†‡ Douglas W. Blayney, MD†‡ UCSF Helen Diller Family Comprehensive Cancer Center Stanford Cancer Institute Ayman A. Saad, MD‡ξ Julio Chavez, MD† University of Alabama at Birmingham Moffitt Cancer Center Comprehensive Cancer Center Peter Curtin, MD‡ξ Lee S. Schwartzberg, MD†‡Þ UC San Diego Moores Cancer Center St. Jude Children’s Research Hospital/ Shira Dinner, MD†‡ The University of Tennessee Health Science Center Robert H. Lurie Comprehensive Cancer Center of Sepideh Shayani, PharmDΣ‡ Northwestern University City of Hope Comprehensive Cancer Center Thomas Fynan, MD† Mahsa Talbott, PharmD‡Σ Yale Cancer Center/Smilow Cancer Hospital Vanderbilt-Ingram Cancer Center Ivana Gojo, MD‡ Saroj Vadhan-Raj, MD†Þ The Sidney Kimmel Comprehensive Cancer Center at The University of Texas MD Anderson Cancer Center Johns Hopkins Sumithira Vasu, MBBS‡ Elizabeth A. Griffiths, MD‡Þ† The Ohio State University Comprehensive Cancer Center – Roswell Park Cancer Institute James Cancer Hospital and Solove Research Institute Shannon Hough, PharmD, BCOPΣ Martha Wadleigh, MD‡† University of Michigan Comprehensive Cancer Center Dana-Farber/Brigham and Women’s Cancer Center Dwight D. Kloth, PharmD, BCOPΣ Peter Westervelt, MD, PhD†ξ‡ Fox Chase Cancer Center Siteman Cancer Center at Barnes-Jewish Hospital and David J. Kuter, MD, DPhil†‡ Washington University School of Medicine Massachusetts General Hospital Cancer Center Gary H. Lyman, MD, MPH, FRCP†‡ NCCN Staff: Jennifer L. Burns, and Lenora Pluchino, PhD Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance KEY: Mary Mably, RPh, BCOPΣ‡ University of Wisconsin Carbone Cancer Center Sudipto Mukherjee, MD, PhD, MPH‡Þ *Discussion Section Writing Committee Case Comprehensive Cancer Center/ Specialties: †Medical Oncology; ‡Hematology/Hematology University Hospitals Seidman Cancer Center oncology; ÞInternal Medicine; ΣPharmacology; ξBone Marrow and Cleveland Clinic Taussig Cancer Institute Transplantation © JNCCN—Journal of the National Comprehensive Cancer Network | Volume 15 Number 12 | December 2017 1522 Myeloid Growth Factors, Version 2.2017 EVALUATION RISK ASSESSMENT d FOR PROPHYLACTIC USE OF G-CSF FOR FEBRILE NEUTROPENIA PRIOR TO FIRST FEBRILE NEUTROPENIA e CURATIVE/ADJUVANT OR PALLIATIVE SETTING f CHEMOTHERAPY CYCLE a,b Granulocyte colony- See Evaluation Prior to Second and High (>20%) stimulating factors Evaluation of • Disease Subsequent Chemotherapy Cycles (MGF-3) (G-CSF) g,h (category 1) risk for febrile • Chemotherapy regimen neutropenia High-dose therapy following Dose-dense therapy Intermediate Consider G-CSF h based See Evaluation of Patient Risk Factors for chemotherapy Standard-dose (10%–20%) on patient risk factors Prophylactic Use (MGF-2) in adult patients therapy with solid tumors • Patient risk factors and non-myeloid • Treatment intent