多发性骨髓瘤靶向新药研究进展

Current Development of Novel Agents for Multiple Myeloma

多发性骨髓瘤(MM)是无法治愈的恶性浆细胞肿瘤。尽管随着免疫调节剂(IMiD)、蛋白酶体抑制剂(PI)等靶向新药的广泛应用,MM患者的预后明显改善,但疾病最终仍会复发进而难治。高危及多重耐药的复发难治性多发性骨髓瘤(RRMM)患者治疗仍面临巨大挑战,亟须针对不同靶点的靶向新药治疗。近10余年来,MM领域靶向新药的研发成果令人瞩目。原有靶向药物的新一代药物,包括第2代PI卡非佐米、第3代IMi D泊马度胺等先后进入临床。免疫治疗领域也取得了长足的进步,针对不同靶点的单克隆抗体、双特异性抗体(Bs Ab)、抗体偶联药物(ADC)及嵌合抗原受体T细胞免疫治疗(CAR-T)效果显著、安全性良好,是MM治疗未来的曙光。随着MM基础研究的深入,针对MM新的不同靶向的药物,如Bcl-2抑制剂、核输出蛋白1(XPO1)抑制剂等先后进入临床试验及临床应用阶段。综述MM领域靶向新药研究进展。

Multiple myeloma(MM) is an incurable plasma cell malignancy. Despite the introduction of novel agents, including immunomodulatory drugs(IMiDs) and proteasome inhibitors(PIs), which have substantially prolonged the prognosis, it will inevitably relapse and become refractory. The high risk, relapsed and refractory MM(RRMM) remains to be the clinical challenge. In the past decade,novel agents have been drastically developed, including the second generation PI(e.g. carfilzomib) and the third generation IMiD(e.g.pomalidomide). Especially, immunotherapy is the promising direction for MM with monoclonal antibodies, bispecific antibody(BsAb),antibody conjugated drug(ACD) and chimeric antigen receptor T-cell immunotherapy(CAR-T) having achieved remarkable efficacy. In addition, with the development of basic research on MM, drugs with new targets, such as Bcl-2 inhibitors, exportin 1(XPO1) inhibitors, etc.,have entered clinical trials or clinical application. This review summarizes the latest treatment progress of novel agents for multiple myeloma.