人力CD20xCD3 Odronextamab双特异性抗体cd20阳性患者b细胞恶性肿瘤(ELM-1):结果从复发或难治性非霍奇金淋巴瘤队列随访时间,多中心,第一阶段试验。

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人力CD20xCD3 Odronextamab双特异性抗体cd20阳性患者b细胞恶性肿瘤(ELM-1):结果从复发或难治性非霍奇金淋巴瘤队列随访时间,多中心,第一阶段试验。

柳叶刀Haematol。2022; 9 (5): e327-e339。doi: 10.1016 / s2352 - 3026 (22) 00072 - 2。Epub 2022 4月1。

PubMed ID
35366963 (在PubMed
]
文摘

背景:Odronextamab hinge-stabilised,完整的人IgG4-based CD20 x CD3双特异性抗体结合CD3在T细胞和B细胞CD20。我们的目的是评估的安全性和抗肿瘤活性odronextamab复发或难治性患者b细胞非霍奇金淋巴瘤。方法:这种单臂,多中心、第一阶段,剂量递增和dose-expansion (ELM-1)审判十点学术网站在美国和德国。患者18岁或以上cd20阳性复发或难治性b细胞恶性肿瘤曾收到CD20-directed抗体疗法和至少一个可测量的损伤,和一个ECOG 0或1的性能状态都包括在内。患者接受静脉注射odronextamab根据升压方案用药周期1,紧随其后的是治疗每周目标从0.1毫克到320毫克剂量在周期2 - 4(每个周期是21天)。周期4后,维持治疗发生每2周,直到疾病进展或不可接受的毒性。安全的主要终点是评估不良事件的发生率和dose-limiting毒性来确定最大耐受剂量或第二阶段odronextamab剂量,或两者兼而有之。初步的抗肿瘤活性,以客观缓解率来衡量,是一个次要的端点。这项研究是在ClinicalTrials.gov注册,NCT02290951。发现:从2月4日,2015年9月25日,2021年,145年严重的患者(平均预处理3(差2 - 5)以前的疗法)登记(94剂量递增和51 dose-expansion研究的一部分)。 The median age of patients was 67.0 years (IQR 57.0-73.0); 101 (70%) were male and 44 (30%) were female; most participants were White (119 [82%]) and not Hispanic or Latino (132 [91%]). 42 (29%) patients received previous CAR T therapy and 119 (82%) were refractory to the last line of therapy. Median duration of follow-up was 4.2 months (IQR 1.5-11.5). During dose escalation, odronextamab was administered up to the maximum dose of 320 mg once per week and no dose-limiting toxicities were observed. The recommended dose for expansion in patients with follicular lymphoma grade 1-3a was 80 mg and was 160 mg for patients with diffuse large B-cell lymphoma. Cytokine release syndrome and neurological treatment-emergent adverse events were predominantly low grade and did not result in treatment discontinuation. The most common grade 3 or worse treatment-emergent adverse events were anaemia (36 [25%]), lymphopenia (28 [19%]), hypophosphataemia (27 [19%]), neutropenia (27 [19%]), and thrombocytopenia (20 [14%]). Serious treatment-emergent adverse events occurred in 89 (61%) of 145 patients; the most frequent were cytokine release syndrome (41 [28%]), pyrexia (11 [8%]), pneumonia (nine [6%]), and infusion-related reaction (six [4%]). Four deaths were considered related to treatment (gastric perforation in a patient with gastric involvement by lymphoma, lung infection, pneumonia, and tumour-lysis syndrome). Objective response rate was 51% (95% CI 42-59; 72 of 142). In patients with follicular lymphoma who received odronextamab doses of 5 mg or higher, the objective response rate was 91% (95% CI 75-98; 29 of 32) and the complete response rate was 72% (95% CI 53-86; 23 of 32). In patients with diffuse large B-cell lymphoma without previous CAR T-cell therapy who received doses of 80 mg or higher, the objective response rate was 53% (eight of 15) and all responses were complete responses. In patients with diffuse large B-cell lymphoma who had previous CAR T-cell therapy and received doses of 80 mg or higher, the objective response rate was 33% (ten of 30) and complete response rate was 27% (eight of 30). INTERPRETATION: Odronextamab monotherapy showed a manageable safety profile and encouraging preliminary activity, including durable responses in heavily pretreated patients with B-cell non-Hodgkin lymphoma, supporting further clinical investigation in phase 2 and 3 trials. FUNDING: Regeneron Pharmaceuticals.

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