Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia
Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia
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DOI：
10.3324/haematol.2011.055822
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发表时间：
2012-05
期刊：
影响因子：
10.1
通讯作者：
R. Walter;B. Medeiros;B. Powell;C. Schiffer;F. Appelbaum;E. Estey
中科院分区：
文献类型：
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作者：
R. Walter;B. Medeiros;B. Powell;C. Schiffer;F. Appelbaum;E. Estey
组蛋白脱乙酰酶抑制剂如伏立诺他增强吉妥珠单抗的体外功效。因此，我们研究了vorinostat+gemtuzumab ozogamicin治疗60岁及以上未经治疗的急性髓性白血病成人。我们将患者分为2组（第1组：年龄≥70岁且体能状态2-3的患者;第2组：年龄60-69岁且体能状态0-3或年龄≥70岁且体能状态0-1）。分别监测第2组细胞遗传学正常或良好（2A组）和其他细胞遗传学（2B组）患者的缓解情况。在31例患者中，6例（19.4%）达到完全缓解，1例（3.2%）达到完全缓解伴血小板不完全恢复;这些患者的中位总生存期高于无应答者（553 vs 131天，P=0.0026）。缓解率为：第1组，10例中有1例（10.0%）;第2A组，13例中有6例（46.2%）;第2B组，8例中无1例（0%）。这些数据表明伏立诺他+吉妥珠单抗奥佐米星具有主要限于正常核型疾病患者的活性。ClinicalTrial.gov：NCT 00673153。
Histone deacetylase inhibitors such as vorinostat enhance gemtuzumab ozogamicin efficacy in vitro. We, therefore, investigated vorinostat+gemtuzumab ozogamicin for adults aged 60 years and over with untreated acute myeloid leukemia. We stratified patients into 2 groups (group 1: patients aged ≥70 years and performance status 2–3; group 2: aged 60–69 years with performance status 0–3 or aged ≥70 years and performance status 0–1). Responses were monitored separately in group 2 patients with normal or favorable cytogenetics (group 2A) and other cytogenetics (group 2B). Among 31 patients, 6 (19.4%) achieved complete remission, and one (3.2%) achieved complete remission with incomplete platelet recovery; these patients had a higher median overall survival than non-responders (553 vs. 131 days, P=0.0026). Response rates were: group 1, one of 10 (10.0%); group 2A, 6 of 13 (46.2%); and group 2B, none of 8 (0%). These data indicate that vorinostat+gemtuzumab ozogamicin has activity that is mostly confined to patients with normal karyotype disease. ClinicalTrial.gov: NCT00673153.