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一项针对复发/难治性多发性骨髓瘤日本患者的1/2期研究,该研究使用人源化BCMA×CD3双特异性抗体teclistamab。

A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

作者信息

Ishida Tadao, Kuroda Yoshiaki, Matsue Kosei, Komeno Takuya, Ishiguro Takuro, Ishikawa Jun, Ito Toshiro, Kosugi Hiroshi, Sunami Kazutaka, Nishikawa Kazuko, Shibayama Kazuhiro, Aida Kensuke, Yamazaki Hiroshi, Inagaki Mitsuo, Kobayashi Hisanori, Iida Shinsuke

机构信息

Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.

Department of Hematology, NHO Hiroshimanishi Medical Center, Otake, Japan.

出版信息

Int J Hematol. 2025 Feb;121(2):222-231. doi: 10.1007/s12185-024-03884-z. Epub 2024 Nov 28.

Abstract

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients.

摘要

我们对双特异性抗体替西妥单抗在日本复发/难治性多发性骨髓瘤(RRMM)患者中的安全性和疗效进行了评估。患者接受过蛋白酶体抑制剂(PI)、免疫调节药物(IMiD)和抗CD38单克隆抗体(mAb)的预处理。主要终点在1期为治疗中出现的不良事件(TEAE)的频率和类型,在2期为总缓解率(ORR;≥部分缓解[PR])。在1期,14例患者接受每周一次(QW)皮下注射替西妥单抗(0.72 mg/kg[n = 5];1.5 mg/kg[n = 5];3 mg/kg[n = 4])。未观察到剂量限制性毒性。截至2024年4月,26例2期患者接受了替西妥单抗的推荐2期剂量(QW)(推荐的2期剂量:1.5 mg/kg)。在维持缓解≥6个月后允许每两周(Q2W)给药一次。在中位随访14.32个月时,ORR为76.9%(≥非常好的PR:76.9%;≥完全缓解:65.4%)。中位缓解持续时间、无进展生存期和总生存期均未达到。常见的TEAE包括CRS(≤2级)、中性粒细胞减少和感染。没有患者出现免疫效应细胞相关神经毒性综合征(ICANS)且无需降低剂量。替西妥单抗在日本RRMM患者中显示出深度且持久的缓解,与全球关键的MajesTEC-1研究结果一致,支持为日本RRMM患者提供新的标准治疗方案的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11782335/9a2985d9cf7f/12185_2024_3884_Fig1_HTML.jpg

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