High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
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DOI：
10.1200/jco.2012.46.2309
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发表时间：
2013-02-20
影响因子：
45.3
通讯作者：
Kantarjian, Hagop
中科院分区：
文献类型：
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作者：
O'Brien, Susan;Schiller, Gary;Kantarjian, Hagop
目的：成人急性淋巴细胞白血病（ALL）的复发与高再诱导死亡率、化疗耐药和快速进展导致死亡相关。硫酸长春新碱脂质体注射（VSLI），鞘磷脂和胆固醇纳米颗粒长春新碱（VCR），促进VCR剂量强化和致密化，并增强靶组织递送。我们评估了高剂量VSLI单药治疗费城染色体（Ph）阴性ALL成人患者的多重复发、复发且难以再诱导和/或造血细胞移植（HCT）后复发。患者和方法在这项关键的II期多国试验中，65名ph阴性ALL患者第二次或更多次复发，或在两次或两次以上白血病治疗后病情进展。静脉注射VSLI 2.25 mg/m(2)，无剂量上限，每周1次，直到反应、进展、毒性或追求HCT。主要终点是达到完全缓解（CR）或CR伴不完全血液学恢复（CRi）。结果CR/CRi率为20%，总有效率为35%。VSLI单药治疗作为三线、四线和五线治疗以及对其他单药和多药再诱导治疗难治性患者有效。中位CR/CRi持续时间为23周（范围5至66周）；12例患者接受了vsli后HCT， 5例患者长期存活。VSLI通常耐受性良好，30天死亡率较低（12%）。结论：大剂量VSLI单药治疗在晚期ALL患者中获得了有意义的临床结果，包括持久的反应和HCT桥接。VSLI的毒性特征是可预测的，可控的，并且与标准VCR相当，尽管提供了大的，通常无法实现的，个体和累积剂量的VCR。[J]中华临床杂志，31(3):676-683。(c) 2012年由美国临床肿瘤学会发布
PurposeRelapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) -negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT).Patients and MethodsSixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m(2), without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi).ResultsThe CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%).ConclusionHigh-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. J Clin Oncol 31:676-683. (c) 2012 by American Society of Clinical Oncology