Department of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Cancer Center, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, Sichuan, China.
West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
BMC Cancer. 2021 May 26;21(1):618. doi: 10.1186/s12885-021-08363-w.
CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects.
We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab.
When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively.
Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
CC 趋化因子受体 4(CCR4)是 CCL22 和 CCL17 的受体,表达于具有最高抗肿瘤免疫反应抑制作用的效应性 Treg 表面。CCR4 也广泛表达于成人 T 细胞白血病/淋巴瘤(ATL)、外周 T 细胞淋巴瘤(PTCL)和皮肤 T 细胞淋巴瘤(CTCL)患者的肿瘤细胞表面。莫格利珠单抗是一种针对 CCR4 的人源化 IgG1κ单克隆抗体。通过减少 CCR4 阳性 Treg 和肿瘤细胞的数量,莫格利珠单抗可以减轻肿瘤负担并增强抗肿瘤免疫反应,从而达到抗肿瘤作用。
我们检索了 PubMed 和 ClinicalTrials.gov 数据库,检索时间截至 2020 年 2 月 1 日。考虑到不同研究之间的变异性,我们选择了不良反应(AE)、总生存期(OS)、无进展生存期(PFS)、客观缓解率(ORR)和 PFS 的危害比(HR)来评估莫格利珠单抗的安全性和疗效特征。
当患者接受莫格利珠单抗单药治疗时,最常见的所有级别不良反应为淋巴细胞减少、输注反应、发热、皮疹和寒战,而最常见的 3 级及以上不良反应为淋巴细胞减少、中性粒细胞减少和皮疹。当患者接受莫格利珠单抗联合其他药物治疗时,最常见的所有级别不良反应为中性粒细胞减少、贫血、淋巴细胞减少和胃肠道紊乱,而最常见的 3 级及以上不良反应为淋巴细胞减少。接受莫格利珠单抗单药治疗的患者,汇总的 ORR 和平均 PFS 分别为 0.430(95%CI:0.393-0.469)和 1.060 个月(95%CI:1.043-1.077)。接受莫格利珠单抗联合其他药物治疗的患者,汇总的 ORR 为 0.203(95%CI:0.022-0.746),而汇总的 PFS 和 OS 分别为 2.093 个月(95%CI:1.602-2.584)和 6.591 个月(95%CI:6.014-7.167)。
基于目前的证据,我们认为莫格利珠单抗具有临床意义的抗肿瘤活性,且毒性可接受,是治疗癌症患者的一种新疗法。