1 Department of Hematology, Oncology, David Geffen School of Medicine at University of California Los Angeles , Los Angeles, California.
2 Department of Hematology and Blood and Marrow Transplant, University of California San Francisco , San Francisco, California.
J Adolesc Young Adult Oncol. 2018 Oct;7(5):546-552. doi: 10.1089/jayao.2018.0041. Epub 2018 Sep 21.
A study of vincristine sulfate (VCR) liposome injection (VSLI) was conducted in patients with advanced, relapsed, or refractory, Philadelphia chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A retrospective subgroup analysis of the results was performed to evaluate the safety and efficacy of VSLI in the adolescent and young adult (AYA) patients.
Of the 65 patients treated in the pivotal Phase 2 Study HBS407 (NCT00495079), 44 patients were aged ≤39 years (median 27 [range 19-39] years) and were included in this analysis. Patients received VSLI (2.25 mg/m intravenously every 7 ± 3 days) without dose capping or concurrent steroid administration in continuous 28-day cycles.
VSLI was well tolerated in the AYA patients over a median of 5 (range 1-15) doses administered. One-third of patients (36%) experienced treatment-related serious adverse events (AEs) with peripheral neuropathy (7%), tumor lysis syndrome (7%), and febrile neutropenia (5%) in >1 patient. Neuropathy-associated AEs occurred in 82% patients; no neuropathy-related deaths occurred. The rate of complete remission (CR) (with or without complete blood count recovery) by investigator assessment was 25% in AYA patients, and the overall response rate was 39%. Median leukemia-free survival in AYA patients attaining CR was 135 (range 32-463) days, and median overall survival was 141 (range 13-620) days.
VSLI provided a meaningful clinical benefit to AYA patients with ALL, and its safety profile was comparable to that of VCR despite the delivery of higher doses (individual and cumulative).
对硫酸长春新碱脂质体注射液（VSLI）治疗费城染色体阴性的晚期、复发或难治性急性淋巴细胞白血病/淋巴细胞白血病（ALL）患者进行了研究。对结果进行了回顾性亚组分析，以评估 VSLI 在青少年和年轻成人（AYA）患者中的安全性和疗效。
在关键的 2 期 HBS407 研究（NCT00495079）中，共有 65 例患者接受了治疗，其中 44 例患者年龄≤39 岁（中位年龄 27 岁[范围 19-39 岁]），并纳入了该分析。患者在 28 天的连续周期中接受 VSLI（2.25mg/m 静脉注射，每 7±3 天一次），不设剂量上限或同时使用皮质类固醇。
AYA 患者接受 VSLI 治疗的中位剂量为 5（范围 1-15），耐受性良好。三分之一（36%）的患者发生了与治疗相关的严重不良事件（AE），其中 7%的患者发生周围神经病，7%的患者发生肿瘤溶解综合征，5%的患者发生发热性中性粒细胞减少症。有 82%的患者发生神经病变相关 AE，无神经病变相关死亡。研究者评估的 AYA 患者完全缓解（CR）率（包括完全血液学恢复和不包括完全血液学恢复）为 25%，总缓解率为 39%。获得 CR 的 AYA 患者白血病无复发生存期中位数为 135（范围 32-463）天，总生存期中位数为 141（范围 13-620）天。
VSLI 为 ALL 的 AYA 患者提供了有意义的临床获益，其安全性与 VCR 相当，尽管剂量较高（个体和累积）。
