A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

被引:377
|
作者
Fenaux, Pierre [1 ]
Giagounidis, Aristoteles [2 ]
Selleslag, Dominik [3 ]
Beyne-Rauzy, Odile [4 ]
Mufti, Ghulam [5 ]
Mittelman, Moshe [6 ]
Muus, Petra [7 ]
Boekhorst, Peter Te [8 ]
Sanz, Guillermo [9 ]
del Canizo, Consuelo [10 ]
Guerci-Bresler, Agnes [11 ]
Nilsson, Lars [12 ]
Platzbecker, Uwe [13 ]
Luebbert, Michael [14 ]
Quesnel, Bruno [15 ]
Cazzola, Mario [16 ]
Ganser, Arnold [17 ]
Bowen, David [18 ]
Schlegelberger, Brigitte [17 ]
Aul, Carlo [2 ]
Knight, Robert [19 ]
Francis, John [19 ]
Fu, Tommy [19 ]
Hellstrom-Lindberg, Eva [20 ]
机构
[1] Univ Paris 13, Hosp Avicenne, AP HP, Serv Hematol Clin, F-93009 Bobigny, France
[2] St Johannes Hosp, Duisburg, Germany
[3] AZ St Jan Brugge AV, Brugge, Belgium
[4] Ctr Hosp Univ Purpan Pavill Med, Toulouse, France
[5] Kings Coll Hosp London, London, England
[6] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel
[7] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
[8] Erasmus MC, Rotterdam, Netherlands
[9] Hosp Univ La Fe, Valencia, Spain
[10] Hosp Univ Salamanca, Salamanca, Spain
[11] Ctr Hosp Univ Nancy Hematol & Med Interne, Vandoeuvre Les Nancy, France
[12] Skane Univ Hosp, Lund, Sweden
[13] Univ Klinikum Carl Gustav Carus, Dresden, Germany
[14] Univ Freiburg, Med Ctr, D-7800 Freiburg, Germany
[15] Ctr Hosp Reg Univ Claude Huriez, Serv Malad Sang, Lille, France
[16] Univ Pavia, Dept Hematol Oncol, Fdn Inst Ricovero & Cura Carattere Sci Policlin S, I-27100 Pavia, Italy
[17] Hannover Med Sch, D-3000 Hannover, Germany
[18] St Jamess Inst Oncol, Leeds, W Yorkshire, England
[19] Celgene Corp, Summit, NJ USA
[20] Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden
关键词
INTERNATIONAL WORKING GROUP; CHROMOSOME 5Q DELETION; FUNCTIONAL ASSESSMENT; RESPONSE CRITERIA; SCORING SYSTEM; MALIGNANCIES; MECHANISM; SURVIVAL; FATIGUE; ANEMIA;
D O I
10.1182/blood-2011-01-330126
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for >= 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for >= 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621. (Blood. 2011; 118(14):3765-3776)
引用
收藏
页码:3765 / 3776
页数:12
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