蛋白酶体抑制剂在多发性骨髓瘤治疗中的应用

Application of proteasome inhibitors in the treatment of multiple myeloma

多发性骨髓瘤(multiple myeloma,MM)为血液系统第二常见的恶性肿瘤。随着对其发病机制的深入研究和新药研发,患者的缓解程度及生存期均获得明显改善。蛋白酶体抑制剂(proteasome inhibitors,PIs)的应用是MM治疗的重要里程碑。硼替佐米的首次出现在临床上显著获益;伊沙佐米作为首个口服PIs,为临床提供了更为便利的治疗手段;新一代卡非佐米由于分子结构的改进和作用机制的优化,可实现更高的获益-风险比。PIs也可在高危MM患者中作为重要的治疗选择。随着PIs类药物的更新迭代和研究证据的积累,此类药物已成为MM治疗的基石,新一代PIs可能为骨髓瘤患者个体化治疗提供更多优化的选择。

Multiple myeloma(MM)is the second most common malignant hematological disorder.Recent advances of bench researches and the development of novel therapeutic agents have led to a dramatic improvement in patients'response and survival.One important milestone is the introduction of proteasome inhibitors(PIs)in the treatmentof MM.As the most selective and reversible PI,bortezomib has shown superior clinical efficacy in the management of MM.Since ixazomib is the first oral PI,it allows for convenient administration in MM patients with good tolerance.The new generation PI,carfilzomib,has a better risk-benefit profile because of improved molecular structure and optimized mechanism of action.In addition,the advantages of PIs in high-risk MM patients render them a superior alternative to standard therapy.In conclusion,with recent advances in the development of PIs and accumulation of supporting evidence,PIs have become the cornerstone of MM treatment.The new generation PIs may provide more optimized alternatives for the individualized treatment of MM patients.