Lin Ningjing, Sun Xiuhua, Zhou Hui, Zou Liqun, Zhou Keshu, Liu Lihong, Yang Haiyan, Hu Kai, Cai Qingqing, Liu Yao, Jin Jie, Zhang Liling, Li Wenyu, Guo Ye, Yang Wei, Luo Feng, Wang Zhenguang, Zhu Rong, Yang Lei, Song Dan, Song Yuqin, Zhu Jun
Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing.
Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian.
Haematologica. 2025 Mar 1;110(3):683-692. doi: 10.3324/haematol.2024.284973.
Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase II LOTIS-2 study. In the China bridging pivotal phase II OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥2 lines of systemic therapies were enrolled and treated every 3 weeks with 150 μg/kg Lonca for two cycles; then 75 μg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by an independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data cutoff, 64 patients received Lonca (median 4.0 cycles; range, 1-17). The median number of prior lines of therapies was 3.0 (range, 2-12). The ORR was 51.6% (95% confidence interval [CI]: 38.7-64.2), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) grade ≥3 treatment-emergent adverse events (TEAE), in which increased γ-glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAE were reported in 35 of 64 patients with four fatal TEAE. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.
复发或难治性(R/R)弥漫性大B细胞淋巴瘤(DLBCL)患者预后较差。Loncastuximab tesirine(Lonca)是一种靶向CD19的抗体偶联物,在一项全球II期LOTIS-2研究中已证明对R/R DLBCL具有显著的临床益处。在中国桥接关键II期OL-ADCT-402-001研究中,纳入了年龄≥18岁、R/R DLBCL且至少2线全身治疗失败的合格患者,每3周接受150μg/kg Lonca治疗两个周期;随后周期为75μg/kg(最长1年)。主要终点是由独立审查委员会评估的总缓解率(ORR)。对接受至少一次治疗且首次记录缓解后至少随访6个月的患者进行疗效和安全性的初步分析。截至数据截止时,64例患者接受了Lonca治疗(中位4.0个周期;范围1-17)。既往治疗线数的中位数为3.0(范围2-12)。ORR为51.6%(95%置信区间[CI]:38.7-64.2),完全缓解率为23.4%。血液学事件占大多数最常见(≥15%)的≥3级治疗中出现的不良事件(TEAE),其中γ-谷氨酰转移酶升高(25.0%)和低钾血症(18.8%)也有报告。64例患者中有35例报告了严重TEAE,4例TEAE导致死亡。总之,Lonca单药治疗在经过大量预处理的中国R/R DLBCL患者中显示出具有临床意义的疗效,且耐受性良好,这与LOTIS-2研究在白种人患者中的结果一致。