Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
MSD.K.K., 1-13-12 Kudan-Kita, Chiyoda-Ku, Tokyo, 102-0073, Japan.
Int J Clin Oncol. 2024 Dec;29(12):1977-1983. doi: 10.1007/s10147-024-02627-8. Epub 2024 Sep 18.
KEYNOTE-A33 (NCT04317066) is an open-label, single-arm, phase 1 trial designed to evaluate the safety and efficacy of pembrolizumab in Japanese patients with relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBCL).
Patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary endpoints were safety and objective response rate (ORR) per International Working Group 2007 criteria by independent central review. The secondary endpoint was disease control rate (DCR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory.
Seven patients were enrolled and treated; the median age was 32 years (range 26-43) and 86% were female. The median time from the first dose to data cutoff (April 12, 2022) was 5.6 months (range 2.4-21.2). Grade 3-5 treatment-related adverse events (AEs) occurred in 2 patients (29%; 2 grade 4 neutropenia, 1 grade 3 febrile neutropenia); however, no patient discontinued pembrolizumab or died because of treatment-related AEs. The ORR was 43% [95% confidence interval (CI) 10-82]. DCR was 57% (95% CI 18-90). Median DOR was not reached (NR). Four (57%) patients had a reduction in target lesion size of ≥ 50%. The median PFS was 2.9 months (95% CI 2.6-NR). The median OS was 17.5 months (95% CI NE-NE), and the 12 months OS rate was 100%.
Overall, pembrolizumab had manageable safety and clinically meaningful antitumor activity in Japanese patients with R/R PMBCL, results that were consistent with those observed in prior global studies.
Registry and the Registration No. of the study/trial: Clinicaltrials.gov: NCT04317066.
KEYNOTE-A33（NCT04317066）是一项开放标签、单臂、1 期临床试验，旨在评估 pembrolizumab 在复发或难治性（R/R）原发性纵隔大 B 细胞淋巴瘤（PMBCL）日本患者中的安全性和疗效。
患者每 3 周接受 200mg pembrolizumab 治疗，最多 35 个周期。主要终点为独立中心审查的国际工作组 2007 标准下的安全性和客观缓解率（ORR）。次要终点为疾病控制率（DCR）。缓解持续时间（DOR）、无进展生存期（PFS）和总生存期（OS）为探索性终点。
7 名患者入组并接受治疗；中位年龄为 32 岁（范围 26-43），86%为女性。从首次给药到数据截止日期（2022 年 4 月 12 日）的中位时间为 5.6 个月（范围 2.4-21.2）。2 名患者（29%；2 级 4 中性粒细胞减少症，1 级 3 发热性中性粒细胞减少症）发生 3-5 级治疗相关不良事件（AE）；然而，没有患者因治疗相关 AE 而停止 pembrolizumab 或死亡。ORR 为 43%（95%CI 10-82）。DCR 为 57%（95%CI 18-90）。中位 DOR 未达到（NR）。4 名（57%）患者靶病灶缩小≥50%。中位 PFS 为 2.9 个月（95%CI 2.6-NR）。中位 OS 为 17.5 个月（95%CI NE-NE），12 个月 OS 率为 100%。
总体而言，pembrolizumab 在 R/R PMBCL 日本患者中具有可管理的安全性和有临床意义的抗肿瘤活性，结果与先前的全球研究一致。
Clinicaltrials.gov：NCT04317066。
