Abstract
G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.
Similar content being viewed by others
References
Goldschmidt H, Ashcroft J, Szabo Z, Garderet L (2019) Navigating the treatment landscape in multiple myeloma: which combinations to use and when? Ann Hematol 98:1–18. https://doi.org/10.1007/s00277-018-3546-8
Martin T, Huff CA (2019) Multiple myeloma: current advances and future directions. Clin Lymphoma Myeloma Leuk 19:255–263
Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905
Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, Malfitano A, Petrò D, Evangelista A, Spada S, Pescosta N, Omedè P, Campbell P, Liberati AM, Offidani M, Ria R, Pulini S, Patriarca F, Hajek R, Spencer A, Boccadoro M, Palumbo A (2015) Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol 16:1617–1629
Cavo M, Palumbo A, Zweegmanet S, Dimopoulos MA, Hajek R, Pantani L et al (2016) Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): a randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). J Clin Oncol 34(15_suppl):8000–8000. https://doi.org/10.1200/JCO.2016.34.15_suppl.8000
Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P,IFM 2009 Study Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017;376:1311–1320
D’Souza A, Lee S, Zhu X, Pasquini M (2017) Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant 23:1417–1421
Passweg JR, Baldomero H, Basak GW, Chabannon C, Corbacioglu S, Duarte R, Kuball J, Lankester A, Montoto S, Latour RP, Snowden JA, Styczynski J, Yakoub-Agha I, Arat M, Mohty M, Kröger N, European Society for Blood and Marrow Transplantation (EBMT) (2019) The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies. Bone Marrow Transplant 54:1575–1585. https://doi.org/10.1038/s41409-019-0465-9
Cavo M, Gay FM, Patriarca F, Zamagni E, Montefusco V, Dozza L et al (2017) Double autologous stem cell transplantation significantly prolongs progression-free survival and overall survival in comparison with single autotransplantation in newly diagnosed multiple myeloma: an analysis of phase 3 EMN02/H095 study. Blood 130(Suppl 1):401
Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan A (2019) Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol 37(7):589–597
Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, Béné MC, Broijl A, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Garderet L, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Lenain P, Macro M, Mathiot C, Orsini-Piocelle F, Perrot A, Stoppa AM, van de Donk N, Wuilleme S, Zweegman S, Kolb B, Touzeau C, Roussel M, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Fermand JP, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Zhuang S, Chiu C, Pei L, de Boer C, Smith E, Deraedt W, Kampfenkel T, Schecter J, Vermeulen J, Avet-Loiseau H, Sonneveld P (2019) Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 394(10192):29–38
Linch DC, Milligan DW, Winfield DA, Kelsey SM, Johnson SA, Littlewood TJ, Smith GM, Hutchinson RM, Goldstone AH, Fielding AK, Vaughan Hudson G (1997) G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial. Br J Haematol 99:933–938
Klumpp TR, Mangan KF, Goldberg SL, Pearlman ES, Macdonald JS (1995) Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial. J Clin Oncol 13:1323–1327
Lee SM, Radford JA, Dobson L, Huq T, Ryder WD, Pettengell R, Morgenstern GR, Scarffe JH, Crowther D (1998) Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin’s lymphoma: clinical benefits at no extra cost. Br J Cancer 77:1294–1299
Spitzer G, Adkins DR, Spencer V, Dunphy FR, Petruska PJ, Velasquez WS, Bowers CE, Kronmueller N, Niemeyer R, McIntyre W (1994) Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit. J Clin Oncol 12:661–670
Trivedi M, Martinez S, Corringham S, Medley K, Ball ED (2011) Review and revision of clinical practice of using G-CSF after autologous and allogeneic hematopoietic stem cell transplantation at UCSD. J Oncol Pharm Pract 17:85–90
NeupogenÕ (filgrastim) [prescribing information]. Thousand Oaks, CA: Amgen Inc, 2012
NeulastaÕ (pegfilgrastim) [prescribing information]. Thousand Oaks, CA: Amgen Inc, 2012
https://www.nccn.org/professionals/physician_gls/default.aspx#supportive
Sebban C, Lefranc A, Perrier L, Moreau P, Espinouse D, Schmidt A et al (2012) A randomised phase II study of the efficacy, safety and cost-effectiveness of pegfilgrastim and filgrastim after autologous stem cell transplant for lymphoma and myeloma (PALM study). Eur J Cancer 48:713–720
Castagna L, Bramanti S, Levis A, Michieli MG, Anastasia A, Mazza R, Giordano L, Sarina B, Todisco E, Gregorini AI, Santoro A (2010) Pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell support. Ann Oncol 21:1482–1485
Ziakas PD, Kourbeti IS (2012) Pegfilgrastim vs. filgrastim for supportive care after autologous stem cell transplantation: can we decide? Clin Transpl 26:16–22
Wannesson L, Luthi F, Zucca E, Rosselet-Christ A, Baglioni M, Marelli L, Ghielmini M, Ketterer N (2011) Pegfilgrastim to accelerate neutrophil engraftment following peripheral blood stem cell transplant and reduce the duration of neutropenia, hospitalization, and use of intravenous antibiotics: a phase II study in multiple myeloma and lymphoma and comparison with filgrastim-treated matched controls. Leuk Lymphoma 52:436–443
Samaras P, Blickenstorfer M, Siciliano RD, Haile SR, Buset EM, Petrausch U, Mischo A, Honegger H, Schanz U, Stussi G, Stahel RA, Knuth A, Stenner-Liewen F, Renner C (2011) Pegfilgrastim reduces the length of hospitalization and the time to engraftment in multiple myeloma patients treated with melphalan 200 and auto-SCT compared with filgrastim. Ann Hematol 90:89–94
Gerds A, Fox-Geiman M, Dawravoo K, Rodriguez T, Toor A, Smith S, Kiley K, Fletcher-Gonzalez D, Hicks C, Stiff P (2010) Randomized phase III trial of pegfilgrastim versus filgrastim after autologus peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 16:678–685
Martino M, Praticò G, Messina G, Irrera G, Massara E, Messina G, Console G, Iacopino P (2006 Nov) Pegfilgrastim compared with filgrastim after high-dose melphalan and autologous hematopoietic peripheral blood stem cell transplantation in multiple myeloma patients. Eur J Haematol 77(5):410–415
https://www.ema.europa.eu/en/documents/product-information/lonquex-epar-product-information_en.pdf
Pan W (2001) Akaike’s information criterion in generalized estimating equations. Biometrics. 57(1):120–125
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR,Infectious Diseases Society of AmericaaClinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011;52:427–431
Lyman GH, Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther2003;1:23–35
Lalami Y, Klastersky J (2017) 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 120:163–179
Lyman GH, Kuderer N, Greene J, Balducci L (1998) The economics of febrile neutropenia: implications for the use of colony stimulating factors. Eur J Cancer 34:1857–1864
Fortner BV, Schwartzberg L, Tauer K, Houts AC, Hackett J, Stolshek BS (2005) Impact of chemotherapy- induced neutropenia on quality of life: a prospective pilot investigation. Support Care Cancer 13:522–528
Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur JCancer 47:8–32
Clark OA, Lyman GH, Castro AA, Clark LG, Djulbegovic B (2005) Colony stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol 23:4198–4214
Kuderer NM, Dale DC, Crawford J, Lyman GH (2007) Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J ClinOncol 25:3158–3167
Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, Huang M, Crawford J (2013) The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol 24:2475–2484
Rifkin R, Spitzer G, Orloff G, Mandanas R, McGaughey D, Zhan F et al (2010) Pegfilgrastim appears equivalent to daily dosing of filgrastim to treat neutropenia after autologous peripheral blood stem cell transplantation in patients with non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 10:186–191
Bondarenko I, Gladkov OA, Elsaesser R, Buchner A, Bias P (2013) Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy. BMC Cancer 13:386
Gladkov OA, Buchner A, Bias P, Müller U, Elsässer R (2016) Chemotherapy associated treatment burden in breast cancer patients receiving lipegfilgrastim or pegfilgrastim: secondary efficacy data from a phase III study. Support Care Cancer 24:395–400
Bondarenko IM, Bias P, Buchner A (2016) Incidence of bone pain in patients with breast cancer treated with lipegfilgrastim or pegfilgrastim: an integrated analysis from phase II and III studies. Support Care Cancer 24:267–273
Ludwig H, Bokemeyer C, Aapro M, Boccadoro M, Gascón P, Denhaerynck K, Krendyukov A, Abraham I, MacDonald K (2019) Chemotherapy induced neutropenia/febrile neutropenia prophylaxis with biosimilar filgrastim in solid tumors versus hematological malignancies: MONITOR-GCSF study. Future Oncol 15(8):897–907
Aagaard T, Reekie J, Roen A, Daugaard G, Specht L, Sengeløv H et al (2019 Mar 6) Development and validation of a cycle-specific risk score for febrile neutropenia during chemotherapy cycles 2-6 in patients with solid cancers: the CSR FENCE score. Int J Cancer. https://doi.org/10.1002/ijc.32249
Bensinger WI, Longin K, Appelbaum F, Rowley S, Weaver C, Lilleby K et al (2019) Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol 87:825–831
Bond TC, Szabo E, Gabriel S, Klastersky J, Tomey O, Mueller U, Schwartzberg L, Tang B (2018 Sep) Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events. J Oncol Pharm Pract 24(6):412–423
Mathew S, Adel N, Rice RD, Panageas K, Duck ET, Comenzo RL et al (2010 Oct) Retrospective comparison of the effects of filgrastim and pegfilgrastim on the pace of engraftment in auto-SCT patients. Bone MarrowTransplant 45(10):1522–1527
Martino M, Montanari M, Bruno B, Console G, Irrera G, Messina G, Offidani M, Scortechini I, Moscato T, Fedele R, Milone G, Castagna L, Olivieri A (2012 Nov) Autologous hematopoietic progenitor cell transplantation for multiple myeloma through an outpatient program. Expert Opin Biol Ther 12(11):1449–1462
Martino M, Montanari M, Ferrara F, Ciceri F, Scortechini I, Palmieri S et al (2014 Jul) Very low rate of readmission after an early discharge outpatient model for autografting in multiple myeloma patients: an Italian multicenter retrospective study. Biol Blood MarrowTransplant 20(7):1026–1032
Martino M, Russo L, Martinello T, Gallo GA, Fedele R, Moscato T, Console G, Vincelli DI, Ronco F, Postorino M, Irrera G, Messina G (2015 Mar) A home-care, early discharge model after autografting in multiple myeloma: results of a three-arm prospective, non-randomized study. Leuk Lymphoma 56(3):801–804
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
The study was approved by the local institutional review board and was conducted according to the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. All patients provided written informed consent before inclusion.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
It was obtained from all patients for being included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Martino, M., Gori, M., Tripepi, G. et al. A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant. Ann Hematol 99, 331–341 (2020). https://doi.org/10.1007/s00277-019-03901-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-019-03901-w