Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group

Annals of Hematology

Volumn 95, Issue 2, 2016, Pages 191-199

  Lübbert, Michael ^a   Suciu, Stefan ^b   Hagemeijer, Anne ^c   Rüter, Björn ^a   Platzbecker, Uwe ^d   Giagounidis, Aristoteles ^e   Selleslag, Dominik ^f   Labar, Boris ^g   Germing, Ulrich ^h   Salih, Helmut R ⁱ   Muus, Petra ^j   Pflüger, Karl Heinz ^k   Schaefer, Hans Eckart ^l   Bogatyreva, Lioudmila ^a,l   Aul, Carlo ^m   de Witte, Theo ^j   Ganser, Arnold ⁿ   Becker, Heiko ^a   Huls, Gerwin ^j,o   van der Helm, Lieke ^o   Vellenga, Edo ^o   Baron, Frédéric ^p   Marie, Jean Pierre ^q   Wijermans, Pierre W ^r   more..

^a UNIVERSITY OF FREIBURG   (Germany)

^b EORTC DATA CENTER   (Belgium)

^c UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^d DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^e MARIEN HOSPITAL DÜSSELDORF   (Germany)

^f AZ Sint Jan Brugge Oostende ^*  (Belgium)

^g KBC Zagreb   (Croatia)

^h HEINRICH HEINE UNIVERSITY   (Germany)

ⁱ UNIVERSITY OF TÜBINGEN   (Germany)

^j RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^k Diako Hospital   (Germany)

^l UNIVERSITY OF FREIBURG   (Germany)

^m ST JOHANNES HOSPITAL   (Germany)

ⁿ HANNOVER MEDICAL SCHOOL   (Germany)

^o UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^p UNIVERSITY OF LIÈGE   (Belgium)

^q SORBONNE UNIVERSITÉ   (France)

^r HAGA HOSPITAL   (Netherlands)

more..

Author keywords

Adverse cytogenetics; Azacytidine; Elderly patients; Epigenetic therapy; Hypomethylating agents; Monosomal karyotype

Indexed keywords

DECITABINE; ANTINEOPLASTIC ANTIMETABOLITE; AZACITIDINE;

AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CHRONIC MYELOMONOCYTIC LEUKEMIA; CONTROLLED STUDY; CYTOGENETICS; FEMALE; GERIATRIC PATIENT; HIGH RISK PATIENT; HUMAN; KARYOTYPE; MAJOR CLINICAL STUDY; MALE; MONOSOMY; MULTIPLE AUTOSOMAL MONOSOMY; MYELODYSPLASTIC SYNDROME; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; REFRACTORY ANEMIA WITH EXCESS BLASTS; REFRACTORY ANEMIA WITH EXCESS BLASTS IN TRANSFORMATION; TREATMENT RESPONSE; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DISEASE COURSE; DISEASE FREE SURVIVAL; EPIDEMIOLOGY; GENETICS; GERMANY; LEUKEMIA; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; RISK FACTOR; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; FEMALE; GERMANY; HUMANS; LEUKEMIA; MALE; MIDDLE AGED; MONOSOMY; MYELODYSPLASTIC SYNDROMES; RISK FACTORS;

EID: 84955197196     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-015-2547-0     Document Type: Article

References (31)

1. Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, Wheatley K (2007) A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 109(6):1114–1124. doi:10.1002/cncr.22496
2. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Lubbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465. doi:10.1182/blood-2012-03-420489
3. Haase D, Germing U, Schanz J, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Kündgen A, Lübbert M, Kunzmann R, Giagounidis AAN, Aul C, Trümper L, Krieger O, Stauder R, Müller TH, Wimazal F, Valent P, Fonatsch C, Steidl C (2007) New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 110(13):4385–4395. doi:10.1182/blood-2007-03-082404
4. Kayser S, Zucknick M, Döhner K, Krauter J, Köhne CH, Horst HA, Held G, von Lilienfeld-Toal M, Wilhelm S, Rummel M, Germing U, Götze K, Nachbaur D, Schlegelberger B, Göhring G, Späth D, Morlok C, Teleanu V, Ganser A, Döhner H, Schlenk RF (2011) Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 119(2):551–558. doi:10.1182/blood-2011-07-367508
5. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD (2009) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European leukemiaNet. Blood 115(3):453–474. doi:10.1182/blood-2009-07-235358
6. Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK (2010) European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol 28(14):2389–2395. doi:10.1200/jco.2009.26.4242
7. Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF (2009) Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 28(4):556–561. doi:10.1200/jco.2009.23.9178
8. Lübbert M, Rüter BH, Claus R, Schmoor C, Schmid M, Germing U, Kuendgen A, Rethwisch V, Ganser A, Platzbecker U, Galm O, Brugger W, Heil G, Hackanson B, Deschler B, Döhner K, Hagemeijer A, Wijermans PW, Döhner H (2012) A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy. Haematologica 97(3):393–401. doi:10.3324/haematol.2011.048231
9. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299. doi:10.1182/blood-2015-01-621664
10. Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10(3):223–232. doi:10.1016/s1470-2045(09)70003-8
11. Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pflüger KH, Coens C, Hagemeijer A, Schaefer HE, Ganser A, Aul C, de Witte T, Wijermans PW (2011) Low-dose decitabine versus best supportive care in elderly patients with Intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European organisation for research and treatment of cancer leukemia group and the German MDS study group. J Clin Oncol 29(15):1987–1996. doi:10.1200/jco.2010.30.9245
12. van der Helm LH, Alhan C, Wijermans PW, van Marwijk KM, Schaafsma R, Biemond BJ, Beeker A, Hoogendoorn M, van Rees BP, de Weerdt O, Wegman J, Libourel WJ, Luykx-de Bakker SA, Minnema MC, Brouwer RE, Croon-de Boer F, Eefting M, Jie K-SG, van de Loosdrecht AA, Koedam J, Veeger NJGM, Vellenga E, Huls G (2011) Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme. Br J Haematol 155(5):599–606. doi:10.1111/j.1365-2141.2011.08893.x
13. Wijermans PW, Lübbert M, Verhoef G, Klimek V, Bosly A (2005) An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol 84(S1):9–17. doi:10.1007/s00277-005-0012-1
14. van der Helm LH, Veeger NJGM, Kooy MM, Beeker A, de Weerdt O, de Groot M, Alhan C, Hoogendoorn M, Laterveer L, van de Loosdrecht AA, Koedam J, Vellenga E, Huls G (2013) Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30% bone marrow blasts. Leuk Res 37(8):877–882. doi:10.1016/j.leukres.2013.03.022
15. Jabbour E, Garcia-Manero G, Ravandi F, Faderl S, O’Brien S, Fullmer A, Cortes JE, Wierda W, Kantarjian H (2013) Prognostic factors associated with disease progression and overall survival in patients with myelodysplastic syndromes treated with decitabine. Clin Lymphoma Myeloma Leuk 13(2):131–138. doi:10.1016/j.clml.2012.11.001
16. Estey EH (2013) Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia. Leukemia 27(9):1803–1812. doi:10.1038/leu.2013.173
17. Lübbert M, Wijermans P, Kunzmann R, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2001) Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 114(2):349–357. doi:10.1111/j.1365-2141.2001.02933.x
18. Rüter B, Wijermans P, Claus R, Kunzmann R, Lübbert M (2007) Preferential cytogenetic response to continuous intravenous low-dose decitabine (DAC) administration in myelodysplastic syndrome with monosomy 7. Blood 110(3):1080–1082. doi:10.1182/blood-2007-03-080630
19. Raj K, John A, Ho A, Chronis C, Khan S, Samuel J, Pomplun S, Thomas NSB, Mufti GJ (2007) CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. Leukemia 21(9):1937–1944. doi:10.1038/sj.leu.2404796
20. Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Grau J, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D (2013) Monosomal karyotype in MDS: explaining the poor prognosis? Leukemia 27(10):1988–1995. doi:10.1038/leu.2013.187
21. Valcarcel D, Adema V, Sole F, Ortega M, Nomdedeu B, Sanz G, Luno E, Canizo C, de la Serna J, Ardanaz M, Marco V, Collado R, Grau J, Montoro J, Mallo M, Vallespi T (2013) Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome. J Clin Oncol 31(7):916–922. doi:10.1200/jco.2012.41.6073
22. Becker H, Suciu S, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Muus P, Pflüger KH, Hagemeijer A, Schaefer HE, Fiaccadori V, Baron F, Ganser A, Aul C, de Witte T, Wijermans PW, Lübbert M (2015) Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt)—results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Ann Hematol 94(12):2003–2013. doi:10.1007/s00277-015-2489-6
23. Breems DA, Van Putten WLJ, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KBJ, Mellink CHM, Nieuwint A, Jotterand M, Hagemeijer A, Beverloo HB, Löwenberg B (2008) Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 26(29):4791–4797. doi:10.1200/jco.2008.16.0259
24. 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 108(2):419–425. doi:10.1182/blood-2005-10-4149
25. Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Löwenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL, World Health Organization (WHO) international working group (2000) Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96(12):3671–3674
26. Wijermans PW, Krulder JWM, Huijgens PC, Neve P (1997) Continuous infusion of low-dose 5-aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia 11(1):1–5. doi:10.1038/sj.leu.2400526
27. Wijermans P, Lübbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2000) Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol Off J Am Soc Clin Oncol 18(5):956–962
28. Kantarjian H, Issa J-PJ, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R, Shen L, Nimer SD, Leavitt R, Raza A, Saba H (2006) Decitabine improves patient outcomes in myelodysplastic syndromes. Cancer 106(8):1794–1803. doi:10.1002/cncr.21792
29. Oosterveld M, Suciu S, Muus P, Germing U, Delforge M, Belhabri A, Aul C, Selleslag D, Ferrant A, Marie JP, Amadori S, Jehn U, Mandelli F, Hess U, Hellström-Lindberg E, Cakmak-Wollgast S, Vignetti M, Labar B, Willemze R, de Witte T (2015) Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies. Ann Hematol 94(1):23–34. doi:10.1007/s00277-014-2177-y
30. Hwang KL, Song MK, Shin HJ, Na HJ, Shin DH, Kim JK, Moon JH, Ahn JS, Song IC, Hong J, Lee GW, Chung JS (2014) Monosomal and complex karyotypes as prognostic parameters in patients with international prognostic scoring system higher risk myelodysplastic syndrome treated with azacitidine. Blood Res 49(4):234–240. doi:10.5045/br.2014.49.4.234
31. Pleyer L, Burgstaller S, Girschikofsky M, Linkesch W, Stauder R, Pfeilstocker M, Schreder M, Tinchon C, Sliwa T, Lang A, Sperr WR, Krippl P, Geissler D, Voskova D, Schlick K, Thaler J, Machherndl-Spandl S, Theiler G, Eckmüllner O, Greil R (2014) Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian azacitidine registry of the AGMT-study group. Ann Hematol 93(11):1825–1838. doi:10.1007/s00277-014-2126-9