Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)

被引:84
作者
Angelucci, Emanuele [1 ]
Santini, Valeria [2 ]
Di Tucci, Anna Angela [1 ]
Quaresmini, Giulia [3 ]
Finelli, Carlo [4 ]
Volpe, Antonio [5 ]
Quarta, Giovanni [6 ]
Rivellini, Flavia [7 ]
Sanpaolo, Grazia [8 ]
Cilloni, Daniela [9 ]
Salvi, Flavia [10 ]
Caocci, Giovanni [11 ]
Molteni, Alfredo [12 ]
Vallisa, Daniele [13 ]
Voso, Maria Teresa [14 ]
Fenu, Susanna [15 ]
Borin, Lorenza [16 ]
Latte, Giancarlo [17 ]
Alimena, Giuliana [18 ]
Storti, Sergio [19 ]
Piciocchi, Alfonso [20 ]
Fazi, Paola [20 ]
Vignetti, Marco [20 ]
Tura, Sante [21 ]
机构
[1] Osped Oncol Riferimento Reg Armando Businco, Hematol & Bone Marrow Transplantat Unit, I-09121 Cagliari, Italy
[2] Univ Florence, Div Hematol, Florence, Italy
[3] Azienda Osped Papa Giovanni XXIII, Hematol & Bone Marrow Transplant Unit, Bergamo, Italy
[4] St Orsola Marcello Malpighi Hosp, Div Hematol, Bologna, Italy
[5] San Giuseppe Moscati Hosp, Div Hematol, Avellino, Italy
[6] Osped A Perrino, Div Hematol, Brindisi, Italy
[7] UO Med Interna & Oncoematol PO Umberto I, Nocera Inferiore, Italy
[8] IRCCS Casa Sollievo Sofferenza, Div Hematol, San Giovanni Rotondo, Italy
[9] Univ Turin, Dept Clin & Biol Sci, Turin, Italy
[10] AO Nazl Santi Antonio & Biagio & C Arrigo, Div Hematol, Alessandria, Italy
[11] R Binaghi Hosp, Bone Marrow Transplantat Ctr, Cagliari, Italy
[12] Osped Niguarda Ca Granda, Div Hematol, Milan, Italy
[13] Hosp Piacenza, Div Med Oncol & Hematol, Piacenza, Italy
[14] Univ Cattolica Sacro Cuore, Div Hematol, Rome, Italy
[15] San Giovanni Hosp, Div Hematol, Rome, Italy
[16] Div Hematol, Monza, Italy
[17] S Francesco Hosp, Div Hematol, Nuoro, Italy
[18] Univ Roma La Sapienza, Div Hematol, I-00185 Rome, Italy
[19] Campobasso Univ, Div Hematol & Med Oncol, Campobasso, Italy
[20] GIMEMA Fdn, GIMEMA Data Ctr, Rome, Italy
[21] Univ Bologna, Bologna, Italy
关键词
serum ferritin; iron chelation; safety; myelodysplastic syndromes; deferasirox; iron overload; chelation therapy; IRON-OVERLOADED PATIENTS; LABILE PLASMA IRON; CHELATION-THERAPY; RESPONSE CRITERIA; MDS PATIENTS; CELLS; RISK; PROGENITORS; GUIDELINES; SURVIVAL;
D O I
10.1111/ejh.12300
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. Methods The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Results Of 159 participants enrolled from 37 Italian centers, 152 received >= 1 dose of deferasirox (initiated at 10-20mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966ng/mL to 1475ng/mL (P<0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12months, respectively. Conclusions Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence.
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收藏
页码:527 / 536
页数:10
相关论文
共 45 条
[11]   Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with β-thalassemia major [J].
Forni, Gian Luca ;
Podesta, Marina ;
Musso, Marco ;
Piaggio, Giovanna ;
Musallam, Khaled M. ;
Balocco, Manuela ;
Pozzi, Sarah ;
Rosa, Alessandra ;
Frassoni, Francesco .
HAEMATOLOGICA, 2013, 98 (04) :555-559
[12]   What are RBC-transfusion-dependence and -independence? [J].
Gale, R. P. ;
Barosi, G. ;
Barbui, T. ;
Cervantes, F. ;
Dohner, K. ;
Dupriez, B. ;
Gupta, V. ;
Harrison, C. ;
Hoffman, R. ;
Kiladjian, J. -J. ;
Mesa, R. ;
Mc Mullin, M. F. ;
Passamonti, F. ;
Ribrag, V. ;
Roboz, G. ;
Saglio, G. ;
Vannucchi, A. ;
Verstovsek, S. .
LEUKEMIA RESEARCH, 2011, 35 (01) :8-11
[13]   Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload [J].
Gattermann, Norbert .
LEUKEMIA RESEARCH, 2007, 31 :S10-S15
[14]   Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes [J].
Gattermann, Norbert ;
Finelli, Carlo ;
Della Porta, Matteo ;
Fenaux, Pierre ;
Stadler, Michael ;
Guerci-Bresler, Agnes ;
Schmid, Mathias ;
Taylor, Kerry ;
Vassilieff, Dominique ;
Habr, Dany ;
Marcellari, Andrea ;
Roubert, Bernard ;
Rose, Christian .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (09) :1364-1371
[15]   Deferasirox treatment of iron-overloaded chelation-naive and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange [J].
Gattermann, Norbert ;
Jarisch, Andrea ;
Schlag, Rudolf ;
Blumenstengel, Klaus ;
Goebeler, Mariele ;
Groschek, Matthias ;
Losem, Christoph ;
Procaccianti, Maria ;
Junkes, Alexia ;
Leismann, Oliver ;
Germing, Ulrich .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2012, 88 (03) :260-268
[16]   Iron overload in MDS-pathophysiology, diagnosis, and complications [J].
Gattermann, Norbert ;
Rachmilewitz, Eliezer A. .
ANNALS OF HEMATOLOGY, 2011, 90 (01) :1-10
[17]   Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study [J].
Gattermann, Norbert ;
Finelli, Carlo ;
Della Porta, Matteo ;
Fenaux, Pierre ;
Ganser, Arnold ;
Guerci-Bresler, Agnes ;
Schmid, Mathias ;
Taylor, Kerry ;
Vassilieff, Dominique ;
Habr, Dany ;
Domokos, Gabor ;
Roubert, Bernard ;
Rose, Christian .
LEUKEMIA RESEARCH, 2010, 34 (09) :1143-1150
[18]   Increased serum hepcidin levels during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndrome [J].
Ghoti, Hussam ;
Fibach, Eitan ;
Westerman, Mark ;
Gordana, Olbina ;
Ganz, Tomas ;
Rachmilewitz, Eliezer A. .
BRITISH JOURNAL OF HAEMATOLOGY, 2011, 153 (01) :118-120
[19]   Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes [J].
Ghoti, Hussam ;
Fibach, Eitan ;
Merkel, Drorit ;
Perez-Avraham, Galit ;
Grisariu, Sigal ;
Rachmilewitz, Eliezer A. .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (08) :1433-1434
[20]   Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences [J].
Glickstein, Hava ;
Ben El, Rinat ;
Link, Gabi ;
Breuer, William ;
Konijn, Abraham M. ;
Hershko, Chaim ;
Nick, Hanspeter ;
Cabantchik, Z. Ioav .
BLOOD, 2006, 108 (09) :3195-3203