在既往多次治疗的复发/难治性毛细胞白血病（HCL）患者中，给予莫昔妥珠单抗帕司努他（moxetumomab pasudotox）治疗：关键性试验的长期随访结果。
Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial.
机构信息
Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
The Royal Marsden Hospital, Downs Road, Sutton, England, UK.
出版信息
J Hematol Oncol. 2021 Feb 24;14(1):35. doi: 10.1186/s13045-020-01004-y.
BACKGROUND
Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).
METHODS
Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days.
RESULTS
Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26-48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3-4 events; these events were generally reversible. No treatment-related deaths were reported.
CONCLUSIONS
Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711.
背景
Moxetumomab pasudotox 是一种靶向 CD22 的重组免疫毒素。在此，我们报告了关键性、多中心、开放标签试验（NCT01829711）的长期随访分析，该试验评估了莫昔妥莫单抗帕苏妥昔在复发性/难治性（R/R）毛细胞白血病（HCL）患者中的应用。
方法
符合条件的患者接受了≥2 种既往全身治疗，包括≥2 种嘌呤核苷类似物（PNAs），或≥1 种 PNA 后接受利妥昔单抗或 BRAF 抑制剂治疗。患者在每个 28 天周期的第 1、3 和 5 天接受 40μg/kg 的莫昔妥莫单抗帕苏妥昔静脉滴注，最多进行 6 个周期。疾病反应和微小残留病（MRD）状态通过盲法独立中心审查确定。主要终点是持久完全缓解（CR），定义为达到 CR 且血液学缓解（HR，CR 的血液计数）持续>180 天。
结果
80 名成年患者接受了莫昔妥莫单抗帕苏妥昔治疗，其中 63%完成了 6 个周期。患者既往接受过中位数为三线的系统治疗；49%为 PNA 难治性，38%不适合接受 PNA 再治疗。在中位随访 24.6 个月时，持久 CR 率（HR 持续>180 天的 CR）为 36%（29 例患者；95%置信区间：26-48%）；HR≥360 天的 CR 率为 33%，总体 CR 率为 41%。27 例完全缓解者（82%）MRD 阴性（所有患者的 34%）。持续≥60 个月的 CR 率为 61%，无 HR 丢失的无进展生存期中位数为 71.7 个月。溶血尿毒综合征和毛细血管渗漏综合征的发生率均≤10%，≤5%的患者发生 3-4 级事件；这些事件通常是可逆的。未报告与治疗相关的死亡。
结论
莫昔妥莫单抗帕苏妥昔在既往接受过多线治疗的 HCL 患者中产生了高比例的持久缓解和 MRD 阴性，具有可管理的安全性特征。因此，它为 R/R HCL 患者提供了一种新的可行治疗选择，这些患者目前缺乏足够的治疗方法。
试验注册
ClinicalTrials.gov 标识符：NCT01829711；首次提交：2013 年 4 月 9 日。https://clinicaltrials.gov/ct2/show/NCT01829711。
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