Abstract
The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by bone marrow failure and a risk of progression to acute myeloid leukemia (AML). Anemia affects the course of disease, quality of life (QOL), and cognitive function of MDS patients. Erythroid-stimulating agents (ESAs) are effective; however, not all patients respond to ESAs. To evaluate the effectiveness of a biosimilar epoetin α (Binocrit) for the treatment of anemia in low-/intermediate-1 risk MDS patients and to evaluate the impact of ESAs on QOL and on cognitive function, 24 consecutive patients aged over 65 years were treated with Binocrit at 40,000 IU once a week for 12 weeks and were followed for at least 3 months. Responsive patients continued with 40,000 IU once a week for a further 12 weeks. Changes in QOL were assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An), while cognitive assessment was carried out by mini-mental state examination (MMSE). All patients completed 12 weeks of therapy. Sixteen patients (66.67 %) achieved an erythroid response (ER), 15 patients (62.5 %) became transfusion independent and remained free from transfusion requirement for at least 3 months, while two patients had reduction in transfusion requirement of at least four RBC transfusions/8 weeks compared with the pretreatment transfusion requirement. Seven patients were nonresponders (29.1 %), of whom four patients were low risk and three intermediate-I risk. Seven transfusion-independent patients were low risk, and eight were intermediate-1 risk. Median hemoglobin (Hb) values were significantly higher after treatment in responders (p < 0.001). ER was maintained after 24 weeks. Statistically significant positive correlations between improvement in Hb and variations in patients’ mini-mental (Spearman’s Rho = 0.54, p < 0.01) and FACT-An scores (Spearman’s Rho = 0.59, p < 0.003) were demonstrated. This preliminary study shows that Binocrit is promising for the treatment of anemia of MDS patients. ER positively correlates with improvements in patients’ cognitive status and positive changes in QOL.
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References
Tefferi A, Vardiman JW (2009) Myelodysplastic syndromes. N Engl J Med 361:1872–1885
Castelli R, Cassin R, Cannavò A, Cugno M (2013) Immunomodulatory drugs: new options for the treatment of myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk 13:1–7
Wright RA, Pantaleo G (2013) Effort processes in achieving performance outcomes: interrelations among and roles of core constructs. Behav Brain Sci 36(6):705–706
Pantaleo G, Miron A, Frankowski S, Ferguson M. Effects of deterrence on intensity of group identification and efforts to protect group identity. Motivation & Emotion, Special Issue on Effort, 2014, in press; ISSN: 0146–7239 EISSN: 1573–6644.
Lamperti E, Pantaleo G, Finocchiaro CY, Silvani A, Botturi A, Gaviani P, Sarno L, Salmaggi A (2012) Recurrent brain tumor: the impact of illness on patient’s life. Support Care Cancer 20:1327–1332
Cazzola M, Malcovati L (2005) Myelodysplastic syndromes-coping with ineffective hematopoiesis. N Engl J Med 352:536–538
Oliva EN, Finelli C, Santini V, Poloni A, Liso V, Cilloni D, Impera S, Terenzi A, Levis A, Cortelezzi A, Ghio R, Musto P, Semenzato G, Clissa C, Lunghi T, Trappolini S, Gaidano V, Salvi F, Reda G, Villani O, Binotto G, Cufari P, Cavalieri E, Spiriti MA (2012) Quality of life and physicians’ perception in myelodysplastic syndromes. Am J Blood Res 2:136–147
Malcovati L (2007) Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 31(suppl 3):S2–S6
Seiter K (2013) Myelodysplasia: new approaches. CurrTreat Options Oncol 14:156–169
Fenaux P, Ades L (2013) How we treat lower-risk myelodysplastic syndromes. Blood 23(121):4280–4286
Kelaidi C, Fenaux P (2010) Darbepoetin alfa in anemia of myelodysplastic syndromes: present and beyond. Expert Opin Biol Ther 10(4):605–614
Abraham I, Mac Donald K (2012) Clinical safety of biosimilar recombinant human erythropoietins. Expert Opin Drug Saf 11:819–840
Bennett CL, Silver SM, Djulbegovic B, Samaras AT, Blau CA, Gleason KJ, Barnato SE, Elverman KM, Courtney DM, McKoy JM, Edwards BJ, Tigue CC, Raisch DW, Yarnold PR, Dorr DA, Kuzel TM, Tallman MS, Trifilio SM, West DP, Lai SY, Henke M (2008) Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 299:914–924
Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, Piper M, Rades D, Steensma DP, Djulbegovic B, Fey MF, Ray-Coquard I, Machtay M, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A (2009) Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet 373:1532–1542
Aapro M (2009) An update on twenty years of anemia management with erythropoiesis-stimulating agents in nephrology and oncology/hematology. Oncologist 14(suppl 1):1
Castelli R, Ferrari B, Cortelezzi A, Guariglia A (2010) Thromboembolic complications in malignant haematological disorders. Curr Vasc Pharmacol 8:482–494
Spiriti MA, Latagliata R, Niscola P, Cortelezzi A, Francesconi M, Ferrari D, Volpe E, Clavio M, Grossi A, Reyes MT, Musto P, Mitra ME, Azzarà A, Pagnini D, D'Arena G, Spadano A, Balleari E, Pecorari P, Capochiani E, De Biasi E, Perego D, Monarca B, Pisani F, Scaramella G, Petti MC (2005) Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome. Ann Hematol 84:167–176
Musto P, Lanza F, Balleari E, Grossi A, Falcone A, Sanpaolo G, Bodenizza C, Scalzulli PR, La Sala A, Campioni D, Ghio R, Cascavilla N, Carella AM (2005) Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol 128:204–209
Kelaidi C, Beyne-Rauzy O, Braun T, Sapena R, Cougoul P, Adès L, Pillard F, Lamberto C, Charniot JC, Guerci A, Choufi B, Stamatoullas A, Slama B, De Renzis B, Ame S, Damaj G, Boyer F, Chaury MP, Legros L, Cheze S, Testu A, Gyan E, Béné MC, Rose C, Dreyfus F, Fenaux P (2013) High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM. Ann Hematol 92:633
Santini V, Schemenau J, Levis A, Balleari E, Sapena R, Adès L, Guerci A, Beyne-Rauzy O, Gourin MP, Cheze S, Stamatoullas A, Sanna A, Gioia D, Cametti G, Ferrero D, Raffoux E, Rose C, Poloni A, Prebet T, Legros L, Natarajan-Amé S, Fenaux P, Germing U, Dreyfus F, Park S (2013) Can the revised IPSS predict response to erythropoietic-stimulating agents in patients with classical IPSS low or intermediate-1 MDS? Blood 122:2286–2288
Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke MJ, Weingart O, Kluge S, Piper M, Napoli M, Rades D, Steensma D, Djulbegovic B, Fey MF, Ray-Coquard I, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A (2009) Erythropoietin or darbepoetin for patients with cancer—meta-analysis based on individual patient data. Cochrane Database Syst Rev 3, CD007303
Haag-Weber M, Vetter A, Thyroff-Friesinger U (2009) Therapeutic equivalence, long term efficacy and safety of HX575 in the treatment of anemia in chronic renal failure patients receiving hemodialysis. ClinNephrol 72:380–e90
Kerkhofs L, Boschetti G, Lugini A, Stanculeanu DL, Palomo AG (2012) Use of biosimilar epoetin to increase hemoglobin levels in patients with chemotherapy-induced anemia: real-life clinical experience. Future Oncol 8:751–756
Abraham I, MacDonald K (2012) Clinical safety of biosimilar recombinant human erythropoietins. Expert Opin Drug Saf 5:819–840
Weise M, Bielsky MC, De Smet K, Ehmann F, Ekman N, Giezen TJ, Gravanis I, Heim HK, Heinonen E, Ho K, Moreau A, Narayanan G, Kruse NA, Reichmann G, Thorpe R, van Aerts L, Vleminckx C, Wadhwa M, Schneider CK (2012) Biosimilars: what clinicians should know. Blood 120:5111–5117
Greenberg PL, Cox C, Le Beau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J (1997) International scoring system for evaluating prognosis of myelodysplastic syndromes. Blood 89:2079–2088
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 15(108):419–425
Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, Gupta V, Harrison C, Hoffman R, Kiladjian JJ, Mesa R, Mc Mullin MF, Passamonti F, Ribrag V, Roboz G, Saglio G, Vannucchi A, Verstovsek S (2011) What are RBC-transfusion-dependence and -independence? Leuk Res 35:8–11
Cella D (1997) The Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 34(3 Suppl 2):13–19
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psych Res 12:189–198
Balleari E, Clavio M, Arboscello E, Bellodi A, Bruzzone A, Del Corso L, Lucchetti MV, Miglino M, Passalia C, Pierri I, Ponassi I, Oneto C, Racchi O, Scudeletti M, Vignolo L, Zoppoli G, Gobbi M, Ghio R (2011) Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes. Leuk Res 35:1472–1476
Villegas A, Arrizabalaga B, Fernández-Lago C, Castro M, Mayans JR, González-Porras JR, Duarte RF, Remacha AF, Luño E, Gasquet JA (2011) Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response. Curr Med Res Opin 27(5):951–960
Park S, Kelaidi C, Sapena R, Vassilieff D, Beyne-Rauzy O, Coiteux V, Vey N, Ravoet C, Cheze S, Rose C, Legros L, Stamatoullas A, Escoffre-Barbe M, Guerci A, Chaury MP, Fenaux P, Dreyfus F (2010) Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res 34:1430–1436
Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di Maio M, Finelli C, Locatelli F, Marchetti M, Morra E, Musto P, Visani G, Tura S (2010) Italian Society of Hematology clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 34:1576–1588
Jädersten M, Malcovati L, Dybedal I, Della Porta MG, Invernizzi R, Montgomery SM, Pascutto C, Porwit A, Cazzola M, Hellström-Lindberg E (2008) Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J ClinOncol 26:3607–3613
Geissler RG, Ganser A (1998) Myelodysplastic syndromes: a guide to treatment with epoetin and colony-stimulating factors. BioDrugs 10:97–109
Groupe Francais des Myelodysplasies, Mannone L, Gardin C, Quarre MC, Bernard JF, Vassilieff D, Ades L, Park S, Vaultier S, Hamza F, Beyne-rauzy MO, Cheze S, Giraudier S, Agape P, Legros L, Voillat L, Dreyfus F, Fenaux P (2006) High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 133:513–519
Musto P, Falcone A, Sanpaolo G, Bodenizza C, La Sala A, Perla G, Carella AM (2003) Efficacy of a single, weekly dose of recombinant erythropoietin in myelodysplastic syndromes. Br J Haematol 122:269–271
Park S, Kelaidi C, Sapena R, Vassilieff D, Beyne-Rauzy O, Coiteux V, Vey N, Ravoet C, Cheze S, Rose C, Legros L, Stamatoullas A, Escoffre-Barbe M, Guerci A, Chaury MP, Fenaux P, Dreyfus F (2010) Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res 34(11):1430–1436
Italian Cooperative Study Group for rHuEpo in Myelodysplastic Syndromes, Ferrini PR, Grossi A, Vannucchi AM, Barosi G, Guarnone R, Piva N, Musto P, Balleari E (1998) A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br J Haematol 103:1070–1074
Raza A, Gezer S, Mundle S, Gao XZ, Alvi S, Borok R, Rifkin S, Iftikhar A, Shetty V, Parcharidou A (1995) Apoptosis in bone marrow biopsy samples involving stromal and hemopoietic cells in 50 patients with myelodysplastic syndromes. Blood 86:268–275
Greenberg PL (1998) Apoptosis and its role in myelodysplastic syndromes: implications for disease natural history and treatment. Leuk Res 22:1123–1136
Aapro M, Cornes P (2012) Diana Sun and Ivo Abraham comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer. Ther Adv Med Oncol 4:95–105
IGES Institute. The competitive role of biosimilars in the German SHI market for pharmaceuticals. 2010
Hong CH, Falvey C, Harris TB, Simonsick EM, Satterfield S, Ferrucci L, Metti AL, Patel KV, Yaffe K (2013) Anemia and risk of dementia in older adults: findings from the Health ABC study. Neurology 81:528–533
Artz AS (2008) Anemia and the frail elderly. Semin Hematol 45:261–266
Lucca U, Tehamanti M, Mosconi P et al (2008) Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the ‘health and anemia study’. PLoS ONE 3:e1920
Denny SD, Kuchibhatla MN, Cohen HJ (2006) Impact of anemia on mortality, cognition and function in community-dwelling elderly. Am J Med 119:327–334
Hare GM (2004) Anaemia and the brain. Curr Opin Anaesthesiol 17:363–369
Merelli A, Czornyj L, Lazarowski A (2013) Erythropoietin: a neuroprotective agent in cerebral hypoxia, neurodegeneration, and epilepsy. Curr Pharm Des 19:6791–6801
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Castelli, R., Deliliers, G.L., Colombo, R. et al. Biosimilar epoetin in elderly patients with low-risk myelodysplastic syndromes improves anemia, quality of life, and brain function. Ann Hematol 93, 1523–1529 (2014). https://doi.org/10.1007/s00277-014-2070-8
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DOI: https://doi.org/10.1007/s00277-014-2070-8