Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q
Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q
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DOI：
10.1182/blood-2007-01-068833
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发表时间：
2008-01-01
期刊：
影响因子：
20.3
通讯作者：
List, Alan F.
中科院分区：
文献类型：
--
作者：
Raza, Azra;Reeves, James A.;List, Alan F.
来那度胺被批准用于治疗由低风险或中等风险1（int-1）骨髓增生异常综合征（MDS）引起的红细胞（RBC）输注依赖性贫血，MDS与染色体5 q缺失相关，伴或不伴其他细胞遗传学异常。我们报告了一项多中心、2期临床试验的结果，该试验评估了来那度胺治疗无5 q缺失的低危或1危MDS输血依赖患者的疗效。符合条件的患者血小板≥ 50000/mm 3，且在前8周内需要≥ 2U RBC; 214例患者接受来那度胺每日10 mg口服或28天周期的第1 - 21天10 mg口服。最常见的3/4级不良事件是中性粒细胞减少症（30%）和血小板减少症（25%）。使用意向治疗分析，56例（26%）患者在中位4.8周治疗后实现了输血独立性（TI），TI的中位持续时间为41.0周。在实现TI的患者中，血红蛋白较基线的中位升高为32 g/L（3.2 g/dL;范围，10-98 g/L [1.0-9.8 g/dL]）。另外37名患者的输血需求减少了50%或更多，血液学改善的总体率为43%（TI反应+输血需求减少>= 50%）。来那度胺在缺乏缺失5 q核型异常的低风险或int 1风险MDS的输血依赖患者中具有临床意义的活性。本研究在www.clinicaltrials.gov上注册，编号为NCT 00064974。
Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent patients with low-or int-1-risk MDS without deletion 5q. Eligible patients had 50000/mm(3) or more platelets and required 2 U or more RBCs within the previous 8 weeks; 214 patients received 10 mg oral lenalidomide daily or 10 mg on days 1 to 21 of a 28-day cycle. The most common grade 3/4 adverse events were neutropenia (30%) and thrombocytopenia (25%). Using an intention-to-treat analysis, 56 (26%) patients achieved transfusion independence (TI) after a median of 4.8 weeks of treatment with a median duration of TI of 41.0 weeks. In patients who achieved TI, the median rise in hemoglobin was 32 g/L (3.2 g/dL; range, 10-98 g/L [1.0-9.8 g/dL]) from baseline. A 50% or greater reduction in transfusion requirement occurred in 37 additional patients, yielding a 43% overall rate of hematologic improvement (TI response +parallel to >= 50% reduction in transfusion requirement). Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1-risk MDS who lack the deletion 5q karyotypic abnormality. This study is registered at www.clinicaltrials.gov as no. NCT00064974.