Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes

被引:109
作者
Sekeres, Mikkael A. [1 ]
Tiu, Ramon V. [1 ]
Komrokji, Rami [2 ]
Lancet, Jeffrey [2 ]
Advani, Anjali S. [1 ]
Afable, Manuel
Englehaupt, Ricki [1 ]
Juersivich, Joyce [1 ]
Cuthbertson, David
Paleveda, Jennifer [2 ]
Tabarroki, Ali
Visconte, Valeria
Makishima, Hideki
Jerez, Andres
Paquette, Ronald [3 ]
List, Alan F. [2 ]
Maciejewski, Jaroslaw P. [1 ]
机构
[1] Cleveland Clin, Taussig Canc Inst, Leukemia Program, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA
[2] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA
[3] Univ Calif Los Angeles, Los Angeles, CA USA
基金
美国国家卫生研究院;
关键词
WORLD-HEALTH-ORGANIZATION; EFFICACY; MDS; CLASSIFICATION; THALIDOMIDE; SAFETY;
D O I
10.1182/blood-2012-06-434639
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lenalidomide and azacitidine each have activity in myelodysplastic syndromes (MDS) patients, where both microenvironment and cell-regulatory mechanisms contribute to disease pathogenesis. The objective of this multicenter, phase 2 expansion trial was to determine the efficacy and safety of combination therapy with azacitidine (75 mg/m(2)/d for 5 days) and lenalidomide (10 mg/d for 21 days; 28-day cycle) in patients with higher-risk MDS. Among 36 patients enrolled (18 phase 1, 18 phase 2), median age was 68 years (range, 47-78 years) and follow-up was 12 months (range, 3-55 years). IPSS categories included intermediate-1 (n = 5 patients with excess blasts), intermediate-2 (20), and high (11). Common grade 3/4 nonhematologic adverse events included febrile neutropenia (22% of patients), other infection (11%), pulmonary (11%), cardiac (11%), constitutional (11%), and dermatologic (11%). The overall response rate (per modified MDS International Working Group criteria) was 72%: 16 patients (44%) achieved a complete response (CR), and 10 (28%) had hematologic improvement. Median CR duration was 17+ months (range, 3-39+); median overall survival was 37+ months (range, 7-55+) for CR patients, and 13.6 months for the entire cohort (range, 3-55). TET2/DNMT3A/IDH1/2 mutational status was associated with response in a limited number of patients. The lenalidomide/azacitidine combination is well-tolerated and highly active in treating greater-risk MDS. This study is registered at http://www.clinicaltrials.gov as NCT00352001. (Blood. 2012; 120(25): 4945-4951)
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收藏
页码:4945 / 4951
页数:7
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