Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma.
Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma.
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DOI：
10.1111/cas.14906
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发表时间：
2021-06
期刊：
影响因子：
5.7
通讯作者：
Tobinai K
中科院分区：
文献类型：
--
作者：
Kawai H;Ando K;Maruyama D;Yamamoto K;Kiyohara E;Terui Y;Fukuhara N;Miyagaki T;Tokura Y;Sakata-Yanagimoto M;Igarashi T;Kuroda J;Fujita J;Uchida T;Ishikawa T;Yonekura K;Kato K;Nakanishi T;Nakai K;Matsunaga R;Tobinai K
E7777是由白喉毒素片段a和B与人白细胞介素‐2组成的重组细胞毒融合蛋白。它的氨基酸序列与didititox相同，但纯度有所提高，活性单体的百分比有所增加。我们在复发或难治性外周T细胞淋巴瘤（PTCL）和皮肤T细胞淋巴瘤（CTCL）患者中开展了一项多中心、单臂II期研究，以评估其疗效、安全性、药代动力学和免疫原性。共纳入37例患者，其中17例为PTCL， 19例为CTCL， 1例为另一种淋巴瘤（结外自然杀伤/T细胞淋巴瘤，鼻型），经中央病理诊断委员会诊断。在36例PTCL和CTCL患者中，基于独立评价的客观缓解率为36%（分别为41%和31%）。中位无进展生存期为3.1个月（PTCL为2.1个月，CTCL为4.2个月）。观察到的常见不良事件（ae）为天冬氨酸转氨酶(AST) /丙氨酸转氨酶（ALT）升高、低白蛋白血症、淋巴细胞减少和发热。我们的研究结果表明，9µg/kg/d剂量的E7777在日本复发或难治性PTCL和CTCL患者中显示出疗效和可管理的安全性，并且在CD25表达范围内观察到临床活性。常见ae是可控的，但ALT / AST升高、低白蛋白血症和毛细血管渗漏综合征应在治疗期间仔细管理。在36例难治性外周T细胞淋巴瘤（PTCL）和皮肤T细胞淋巴瘤（CTCL）患者中，基于独立评价的客观缓解率为36% （PTCL为41%，CTCL为31%）。我们的研究结果表明，9µg/kg/d剂量的E7777在日本复发或难治性PTCL和CTCL患者中显示出疗效和可管理的安全性，并且在CD25表达范围内观察到临床活性。常见的不良事件是可控的，但在治疗过程中应小心处理谷丙转氨酶/天冬氨酸转氨酶升高、低白蛋白血症和毛细血管渗漏综合征。
E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin‐2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We undertook a multicenter, single‐arm phase II study of E7777 in patients with relapsed or refractory peripheral T‐cell lymphoma (PTCL) and cutaneous T‐cell lymphoma (CTCL) to evaluate its efficacy, safety, pharmacokinetics, and immunogenicity. A total of 37 patients were enrolled, of which 17 and 19 patients had PTCL and CTCL, respectively, and one patient with another type of lymphoma (extranodal natural killer/T‐cell lymphoma, nasal type), diagnosed by the Central Pathological Diagnosis Committee. Among the 36 patients with PTCL and CTCL, objective response rate based on the independent review was 36% (41% and 31%, respectively). The median progression‐free survival was 3.1 months (2.1 months in PTCL and 4.2 months in CTCL). The common adverse events (AEs) observed were increased aspartate aminotransferase (AST) / alanine aminotransferase (ALT), hypoalbuminemia, lymphopenia, and pyrexia. Our results indicated that a 9 µg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common AEs were manageable, but increase in ALT / AST, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment. Among 36 patients with refractory peripheral T‐cell lymphoma (PTCL) and cutaneous T‐cell lymphoma (CTCL), objective response rate based on the independent review was 36% (41% in PTCL and 31% in CTCL). Our results indicated that a 9 µg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common adverse events were manageable, but increase in alanine aminotransferase / aspartate aminotransferase, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment.
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罗米地辛治疗复发/难治性外周 T 细胞淋巴瘤：关键研究更新表明持久反应。
影响因子：
28.5
作者：
Coiffier B;Pro B;Prince HM;Foss F;Sokol L;Greenwood M;Caballero D;Morschhauser F;Wilhelm M;Pinter-Brown L;Padmanabhan Iyer S;Shustov A;Nielsen T;Nichols J;Wolfson J;Balser B;Horwitz S
通讯作者：
Horwitz S
影响因子：
45.3
作者：
Piekarz, Richard L.;Frye, Robin;Bates, Susan E.
通讯作者：
Bates, Susan E.
影响因子：
45.3
作者：
Prince, H. Miles;Duvic, Madeleine;Negro-Vilar, Andres
通讯作者：
Negro-Vilar, Andres
影响因子：
45.3
作者：
Pro, Barbara;Advani, Ranjana;Shustov, Andrei
通讯作者：
Shustov, Andrei
影响因子：
5.7
作者：
Ohmachi, Ken;Ando, Kiyoshi;Nakanishi, Tadashi
通讯作者：
Nakanishi, Tadashi