Nishimura Noriko, Terui Yasuhito, Hatake Kiyohiko
Division of Hematology Oncology, Cancer Institute Hospital of the Japanese Society for Cancer Research.
Rinsho Ketsueki. 2017;58(8):1006-1013. doi: 10.11406/rinketsu.58.1006.
Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies. More favorable results of phase 3 study of 16 mg/kg daratumumab with lenalidomide and dexamethasone revealed that 92.9% of patients with RRMM achieved at least partial response (PR), with a 43.1% complete response (CR) rate. The median PFS was better in daratumumab arm (Not Reached) than control arm (18.4 months). When combined with lenalidomide plus dexamethasone, elotuzumab, at a dose of 10 mg/kg, improved the median PFS from 14.9 months to 19.4 months in a phase 3 study named ELOQUENT-2. In addition to IMiDs, bortezomib was a hopeful partner. Regarding toxicity, these mAbs are tolerable even in elderly patients. The most common adverse event is an infusion-related reaction. Based on several published reports, we suggest that mAbs combined with standard agents could be successfully adapted for the treatment of newly diagnosed patients with MM.
具有新作用机制的单克隆抗体(mAb)正在成为治疗多发性骨髓瘤(MM)患者的有前景的药物。其中,抗CD38抗体和抗信号淋巴细胞激活分子F7(SLAMF7)抗体已证明对复发难治性骨髓瘤(RRMM)有效。两种靶向CD38的抗体,达雷妥尤单抗和isatuximab作为单药具有显著活性,而靶向SLAMF7的抗体埃罗妥珠单抗则不然。在两项不同的2期研究中,接受16mg/kg达雷妥尤单抗治疗的RRMM患者至少达到部分缓解(PR)的比例分别为36%和29%。16mg/kg达雷妥尤单抗与来那度胺和地塞米松联合的3期研究结果更令人满意,显示92.9%的RRMM患者至少达到部分缓解(PR),完全缓解(CR)率为43.1%。达雷妥尤单抗组的中位无进展生存期(PFS)更好(未达到),优于对照组(18.4个月)。在一项名为ELOQUENT-2的3期研究中,当与来那度胺加地塞米松联合使用时,10mg/kg剂量的埃罗妥珠单抗将中位PFS从14.9个月提高到了19.4个月。除了免疫调节药物(IMiD),硼替佐米也是一个有希望的联合用药伙伴。关于毒性,这些单克隆抗体即使在老年患者中也是可耐受的。最常见的不良事件是输液相关反应。基于多篇已发表的报告,我们建议单克隆抗体与标准药物联合可成功应用于新诊断MM患者的治疗。