<br>单药皮下注射 blinatumomab 治疗晚期急性淋巴细胞白血病,American Journal of Hematology

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单药皮下注射 blinatumomab 治疗晚期急性淋巴细胞白血病
American Journal of Hematology ( IF 10.1 ) Pub Date : 2024-02-05 , DOI: 10.1002/ajh.27227
Elias Jabbour ₁ , Gerhard Zugmaier ₂ , Vaibhav Agrawal ₃ , Pilar Martínez-Sánchez ₄ , José J Rifón Roca ₅ , Ryan D Cassaday _{6,

7} , Boris Böll ₈ , Anita Rijneveld ₉ , Maher Abdul-Hay ₁₀ , Françoise Huguet ₁₁ , Thomas Cluzeau ₁₂ , Mar Tormo Díaz ₁₃ , Vladan Vucinic ₁₄ , José González-Campos ₁₅ , Alessandro Rambaldi ₁₆ , Stefan Schwartz ₁₇ , Céline Berthon ₁₈ , Jesús María Hernández-Rivas _{19,

20,

21} , Paul R Gordon ₂₂ , Monika Brüggemann ₂₃ , Ali Hamidi ₂₂ , Yuqi Chen ₂₂ , Hansen L Wong ₂₄ , Bharat Panwar ₂₂ , Yuliya Katlinskaya ₂₂ , Ana Markovic ₂₂ , Hagop Kantarjian ₁

Affiliation

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amgen Research (Munich), GmbH, Munich, Germany.
Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, California, USA.
Department of Hematology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), CNIO, CIBERONC, Madrid, Spain.
Hematology and Hemotherapy Department, Clínica Universidad de Navarra, Pamplona, Spain.
Division of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
First Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, University of Cologne, Cologne, Germany.
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
Perlmutter Cancer Center, New York University Langone Health, New York, New York, USA.
Department of Hematology, Institut Universitaire du Cancer-Oncopole CHU de Toulouse, Toulouse, France.
Université Nice Côte d'Azur, CHU de Nice, Nice, France.
Hematology Department, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
Department of Hematology and Cell Therapy, University Hospital Leipzig, Leipzig, Germany.
Hematology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Department of Oncology-Hematology, University of Milan, Milan and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
Centre Hospitalier Universitaire de Lille, Lille, France.
IBSAL, IBMCC, CSIC, Cancer Research Center, University of Salamanca, Salamanca, Spain.
Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
CIBERONC, Research Group CB16/12/00233, Salamanca, Spain.
Amgen Inc., Thousand Oaks, California, USA.
Department of Hematology, University of Schleswig-Holstein, Kiel, Germany.
Clinical Pharmacology, Modeling and Simulation, Amgen Inc., South San Francisco, California, USA.

Blinatumomab 是一种 BiTE®（双特异性 T 细胞接合器）分子，可重定向 CD3 ⁺ T 细胞以接合并裂解 CD19 ⁺靶细胞。在这里，我们证明皮下注射 (SC) blinatumomab 可以提供高效且更方便的给药。在一项多机构 1b 期试验的扩展阶段（ClinicalTrials.gov，NCT04521231），患有复发/难治性 B 细胞急性淋巴细胞白血病 (R/R B-ALL) 的经过严格预处理的成人接受了两种剂量的 SC blinatumomab 治疗：(1 ) 第 1 周每日一次 (QD) 250 μg，此后每周三次 (TIW) 500 μg (250 μg/500 μg) 或 (2) 第 1 周 QD 500 μg，此后 TIW 1000 μg (500 μg/1000 μg) 。主要终点是两个周期内完全缓解/部分血液学恢复的完全缓解（CR/CRh）。截至 2023 年 9 月 15 日数据截止，共有 29 名患者接受了治疗：其中 14 名患者接受 250 μg/500 μg 剂量治疗，13 名患者接受 500 μg/1000 μg 剂量治疗。两名不符合条件的患者的数据被排除在外。两个周期结束时，接受 250 μg/500 μg 剂量的 14 名患者中有 12 名 (85.7%) 达到 CR/CRh，其中 9 名患者 (75.0%) 可测量残留病灶 (MRD；<10 id=122> −4 白血病细胞）。在500μg/1000μg剂量下，13名患者中有12名（92.3%）达到CR/CRh；所有 12 名患者 (100.0%) 均为 MRD 阴性。没有报告与治疗相关的 4 级细胞因子释放综合征 (CRS) 或神经系统事件 (NE)。 SC 注射耐受性良好，所有与治疗相关的 3 级 CRS 和 NE 对标准护理管理、中断或停药均有反应。 SC blinatumomab 治疗对经过大量预处理的 R/R B-ALL 成人患者具有较高的疗效、较高的 MRD 阴性率和可接受的安全性。

"点击查看英文标题和摘要"

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3⁺ T-cells to engage and lyse CD19⁺ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 μg once daily (QD) for week 1 and 500 μg three times weekly (TIW) thereafter (250 μg/500 μg) or (2) 500 μg QD for week 1 and 1000 μg TIW thereafter (500 μg/1000 μg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 μg/500 μg dose and 13 at 500 μg/1000 μg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 μg/500 μg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10⁻⁴ leukemic blasts). At the 500 μg/1000 μg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

更新日期：2024-02-05

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