Inhibition of high CXCR4 with motixafortide and absence of single-cell MRD predict outcome after AML consolidation.

The bone marrow (BM) microenvironment, largely orchestrated by the CXC chemokine receptor 4 (CXCR4)-CXC motif chemokine 12 axis (CXCL12), enables leukemia cell survival and chemoresistance by anchoring blasts in their protective BM niche.

骨髓（BM）微环境主要由CXC趋化因子受体4（CXCR4）-CXC基序趋化因子12轴（CXCL12）调控，通过将白血病细胞锚定在其保护性的BM生态位中，使白血病细胞得以存活并产生化疗耐药性。

Motixafortide, a selective CXCR4 antagonist, mobilizes leukemic cells and disrupts tumor microenvironment interactions in preclinical models.

Motixafortide是一种选择性CXCR4拮抗剂，在临床前模型中能够动员白血病细胞并破坏肿瘤微环境的相互作用。

In this randomized, double-blind, placebo-controlledphase 2 trial, 128 patients in first remission received high-dose cytarabine plus motixafortide or placebo.

在这项随机、双盲、安慰剂对照的2期临床试验中，128名首次缓解的患者接受了高剂量的阿糖胞苷加上Motixafortide或安慰剂。

Median relapse-free survival did not substantially differ between groups: 10.3 months (95% confidence interval[CI], 8.0-12.0) for motixafortide and 11.5 months (95% CI, 8.6-24.1) for placebo (log-rank P = .98).

两组之间的中位无复发生存期没有显著差异：motixafortide组为10.3个月（95%置信区间[CI]，8.0-12.0），安慰剂组为11.5个月（95% CI，8.6-24.1）（对数秩检验P = .98）。

But single-cell measurable residual disease (scMRD) analysis, performed before consolidation, demonstrated heterogeneity of CXCR4 inhibition benefit; in the placebo group, higher CXCR4 expression was associated with increased relapse risk (P = .02), whereas in the motixafortide group, higher CXCR4 expression was linked to a reduced relapse rate (P = .047).

但在巩固治疗前进行的单细胞可测量残余疾病（scMRD）分析显示，CXCR4抑制的益处存在异质性；在安慰剂组中，较高的CXCR4表达与增加的复发风险相关（P = .02），而在motixafortide组中，较高的CXCR4表达与降低的复发率相关（P = .047）。

Exploratory analyses identified scMRD levels at which higher MRD burden was associated with inferior overall survival. Taken together, combining functional MRD profiling with biomarker-driven patient selection, such as CXCR4 expression, may enable more precise and effective postremission interventions in AML.

探索性分析确定了在微小残留病灶（scMRD）水平较高时，更高的MRD负担与较差的总生存相关。综合来看，结合功能性MRD分析和基于生物标志物的患者选择，例如CXCR4表达，可能使急性髓细胞性白血病（AML）的缓解后干预更加精确和有效。

This trial was registered at www.clinicaltrials.gov as NCT02502968 and at EudraCT as 2014-002702-21.

该试验已在www.clinicaltrials.gov上注册，注册号为NCT02502968，在EudraCT上的注册号为2014-002702-21。