INO-VATE 研究中复发/难治性急性淋巴细胞白血病患者按年龄队列分析英妥珠单抗奥唑米星的疗效和安全性。

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.

出版信息

Cancer. 2018 Apr 15;124(8):1722-1732. doi: 10.1002/cncr.31249. Epub 2018 Jan 30.

DOI:10.1002/cncr.31249

PMID:29381191

Abstract

BACKGROUND

Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients.

METHODS

Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment. Of the 326 patients, 164 received InO at a starting dose of 1.8 mg/m /cycle (0.8 mg/m on day 1 and 0.5 mg/m on days 8 and 15 of a 21- to 28-day cycle [≤6 cycles]); 60 patients were aged ≥55 years, and 104 were aged <55 years.

RESULTS

For older and younger patients, the median duration of InO therapy and the types and frequencies of adverse events of any grade were generally similar. Although the remission rates, median duration of remission (DOR), and progression-free survival were similar with InO for those aged <55 years and those aged ≥55 years, OS was longer for younger patients (median, 8.6 vs 5.6 months; hazard ratio, 0.610). Among patients proceeding to hematopoietic stem cell transplantation after InO treatment (28% of older patients and 58% of younger patients), the incidence of veno-occlusive disease was greater in older patients (41% vs 17%). The study database was not locked at the time of this analysis.

CONCLUSIONS

InO was tolerable in older patients with relapsed/refractory ALL. Although OS was longer for younger patients versus older patients, InO demonstrated high response rates with similar DOR in the 2 age groups. Cancer 2018;124:1722-32. © 2018 American Cancer Society.

摘要

背景

依妥珠单抗奥佐米星（InO）在 INO-VATE 试验中，在 18 岁至 78 岁的复发/难治性急性淋巴细胞白血病（ALL）患者中显示出疗效和耐受性。这项亚组分析比较了 InO 在年轻患者和老年患者中的疗效和安全性。

方法

意向治疗分析形态学反应和总生存（OS）包括 326 名随机患者，安全性评估包括 307 名接受 1 次或多次研究治疗的患者。在 326 名患者中，164 名患者起始剂量为 1.8mg/m /周期（第 1 天 0.8mg/m，第 8 天和第 15 天 0.5mg/m，周期为 21 至 28 天[≤6 个周期]）；60 名患者年龄≥55 岁，104 名患者年龄<55 岁。

结果

对于老年和年轻患者，InO 治疗的中位持续时间以及任何级别不良事件的类型和频率通常相似。尽管年轻患者和年龄≥55 岁患者的缓解率、中位缓解持续时间（DOR）和无进展生存期与 InO 相似，但年轻患者的 OS 更长（中位数 8.6 个月 vs 5.6 个月；风险比，0.610）。在接受 InO 治疗后进行造血干细胞移植的患者中（老年患者 28%，年轻患者 58%），老年患者静脉闭塞性疾病的发生率更高（41% vs 17%）。在进行本次分析时，研究数据库尚未锁定。