BIOLOGIC EFFECTS OF ANTI-INTERLEUKIN-6 MURINE MONOCLONAL-ANTIBODY IN ADVANCED MULTIPLE-MYELOMA
BIOLOGIC EFFECTS OF ANTI-INTERLEUKIN-6 MURINE MONOCLONAL-ANTIBODY IN ADVANCED MULTIPLE-MYELOMA
复制标题
DOI：
10.1182/blood.v86.2.685.bloodjournal862685
复制
发表时间：
1995-07-15
期刊：
影响因子：
20.3
通讯作者：
KLEIN, B
中科院分区：
文献类型：
--
作者：
BATAILLE, R;BARLOGIE, B;KLEIN, B
在晚期多发性骨髓瘤（MM）患者中，体内白细胞介素-6（IL-6）产生过量，血清水平升高与血浆白细胞介素增殖活性和短生存期相关。这些数据促使我们用鼠抗IL-6单克隆抗体（MoAb）进行临床试验，以中和这些患者中过量的这种有害因子。10例多发性骨髓瘤患者经常髓外受累，用抗IL-6单抗治疗。9例患者静脉注射MoAb; 1例恶性胸腔积液患者接受胸腔内治疗。在治疗不到1周后死于进展性MM的3例患者中（包括仅1例局部治疗的患者），2例具有可评价数据的患者表现出明显的血浆抗体增殖抑制。在接受抗IL-6单克隆抗体治疗超过1周的7例患者中，3例患者具有客观的抗增殖作用，其特征在于骨髓内骨髓瘤细胞标记指数显著降低。这3例患者中有1例实现了30%的肿瘤质量消退。然而，根据标准临床标准判断，研究的患者均未达到缓解或改善的结局。主要关注的是，客观的抗增殖作用与完全抑制C-反应蛋白（CRP）的合成和低的每日IL-6在体内的生产。另一方面，在4例患者中缺乏效果与较高的IL-6产生和MoAb无法中和它有关。抗IL-6也与所有患者的低热消退以及血小板减少症和轻度中性粒细胞减少症的恶化有关。在1例患者中观察到的针对鼠抗IL-6 MoAb Fc片段的人抗体的产生与显著进展相关。这些数据表明，抗IL-6单克隆抗体可以抑制骨髓瘤细胞的增殖，并强调了IL-6在体内骨髓瘤生长中的生物学作用。此外，CRP的抑制和中性粒细胞减少/血小板减少的恶化均表明IL-6与急性期反应和粒细胞生成/血小板生成密切相关。(C)1995年，美国血液学会。
In patients with advanced multiple myeloma (MM) there is an excess of production of interleukin-6 (IL-6) in vivo, and elevated serum levels are associated with plasmablastic proliferative activity and short survival. These data prompted us to perform a clinical trial with a murine anti-IL-6 monoclonal antibody (MoAb) to neutralize the excess of this putatively deleterious factor in these patients. Ten MM patients with extramedullary involvement frequently were treated with anti-IL-6 MoAb. The MoAb was administered intravenously to 9 patients; 1 patient with malignant pleural effusion received intrapleural therapy. Of the 3 patients who succumbed to progressive MM after less than 1 week of treatment (including the only 1 treated locally), 2 with evaluable data exhibited marked inhibition of plasmablastic proliferation. Among the 7 patients remaining more homogeneous receiving the anti-IL-6 MoAb for more than 1 week, 3 had objective antiproliferative effect marked by a significant reduction of the myeloma cell labelling index within the bone marrow. One of these 3 patients achieved a 30% regression of tumor mass. However, none of the patients studied achieved remission or improved outcome as judged by standard clinical criteria. Of major interest, objective antiproliferative effects were associated with complete inhibition of C-reactive protein (CRP) synthesis and low daily IL-6 production in vivo. On the other hand, the lack of effect in 4 patients was associated with a higher IL-6 production and inability of the MoAb to neutralize it. Anti-IL-6 was also associated with resolution of low-grade fever in all the patients and with worsening thrombocytopenia and mild neutropenia. The generation of human antibodies to Fc fragment of the murine anti-IL-6 MoAb observed in 1 patient was associated with dramatic progression. These data show that anti-IL-6 MoAb can suppress the proliferation of myeloma cells and underscore the biologic role of IL-6 for myeloma growth in vivo. Furthermore, suppression of CRP and worsening of neutropenia/thrombocytopenia both indicate that IL-6 is critically involved in acute-phase responses and granulopoiesis/thrombopoiesis. (C) 1995 by The American Society of Hematology.