Liu Weiping, Li Yufu, Wang Quanshun, Su Hang, Ding Kaiyang, Shuang Yuerong, Gao Sujun, Zou Dehui, Jing Hongmei, Chai Ye, Zhang Yicheng, Liu Lihong, Wang Chunling, Liu Hui, Lin Jinying, Zhu Haiyan, Yao Chen, Yan Xiaoyan, Shang Meixia, Wang Shufang, Chang Fengyuan, Wang Xiaopei, Zhu Jun, Song Yuqin
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Hematology, Henan Cancer Hospital, Zhengzhou, China.
Front Med (Lausanne). 2021 Feb 2;8:609116. doi: 10.3389/fmed.2021.609116. eCollection 2021.
YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients. This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9-10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 10/kg CD34 HSCs within ≤4 apheresis sessions. In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively ( < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 10/kg CD34 HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, < 0.001). Furthermore, the median time to collect ≥2 or 5 × 10/kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups. YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.
YF-H-2015005是一种新型CXCR4拮抗剂，已被证明可增加循环造血干细胞（HSC）的数量，从而使非霍奇金淋巴瘤（NHL）患者能够充分采集造血干细胞。这是一项多中心、双盲、随机（1:1）、安慰剂对照的III期临床试验。所有患者连续8天接受粒细胞集落刺激因子（G-CSF）治疗。YF-H-2015005或安慰剂在第4天晚上给药，持续每日给药最多4天。每次给予YF-H-2015005或安慰剂后9-10小时进行单采。主要终点是NHL患者在≤4次单采疗程内采集到≥5×10⁶/kg CD34⁺造血干细胞的比例。总共招募了101例NHL患者。YF-H-2015005组和安慰剂组达到主要终点的患者比例分别为57%和12%（P<0.001）。此外，与安慰剂治疗的患者相比，接受YF-H-2015005治疗的患者在≤4个单采日内达到≥2×10⁶/kg CD34⁺造血干细胞的最低目标采集量的比例更高（86%对38%，P<0.001）。此外，YF-H-2015005治疗的患者采集到≥2×10⁶/kg或≥5×10⁶/kg CD34⁺造血干细胞的中位时间分别为1天和3天，而安慰剂治疗的患者分别为4天且未达到。在YF-H-2015005治疗组和安慰剂组中均未观察到严重的治疗突发不良事件。YF-H-2015005加G-CSF方案是一种耐受性良好且疗效高的联合方案，可用于快速动员和采集NHL患者的造血干细胞。
