Leonard J P, Friedberg J W, Younes A, Fisher D, Gordon L I, Moore J, Czuczman M, Miller T, Stiff P, Cheson B D, Forero-Torres A, Chieffo N, McKinney B, Finucane D, Molina A
Division of Hematology/Oncology, Weill Medical College of Cornell University and NewYork-Presbyterian Hospital, New York, NY 10021, USA.
Ann Oncol. 2007 Jul;18(7):1216-23. doi: 10.1093/annonc/mdm114. Epub 2007 Apr 29.
Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated.
Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response.
Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics.
These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.
加利昔单抗是一种靶向CD80的单克隆抗体，CD80是一种在滤泡性淋巴瘤和其他淋巴瘤中组成性表达的共刺激分子。在一项针对复发或难治性滤泡性非霍奇金淋巴瘤（NHL）的I期研究中，显示出了适度的单药临床活性和耐受性。开展了一项I/II期研究，以评估加利昔单抗联合标准疗程利妥昔单抗的疗效。对安全性、药代动力学和疗效进行了评估。
纳入复发或一线治疗失败的滤泡性NHL患者。排除对利妥昔单抗难治的患者（无反应或反应后疾病进展时间<6个月）。患者接受4次静脉输注加利昔单抗（125、250、375或500mg/m²）和利妥昔单抗（375mg/m²），每周1次。采用国际研讨会反应标准（IWRC）评估反应。
73例患者接受了治疗。所有患者均至少接受过一次先前的淋巴瘤治疗；40%为初治利妥昔单抗患者。输注在门诊进行，耐受性良好。最常见的与研究相关的不良事件（AE）为淋巴细胞减少、白细胞减少、中性粒细胞减少、疲劳和寒战。加利昔单抗推荐的II期剂量（500mg/m²）时的总缓解率为66%：完全缓解率为19%，未确认的完全缓解率为14%，部分缓解率为33%。中位无进展生存期为12.1个月。联合治疗似乎未改变药代动力学。
这些结果表明，加利昔单抗可与标准疗程的利妥昔单抗安全联合使用。这种双生物制剂方法有可能避免或延迟化疗，或与其他淋巴瘤治疗方法相结合。一项评估利妥昔单抗与联合治疗临床获益的III期随机研究已经启动。
