侯健-多发性骨髓瘤转化医学研究.pptVIP

蛋白酶体抑制剂的作用机制是调节NF-kB？ 多种肿瘤NF-kB活性升高，为何MM效果特别好？ 为何NF-kB抑制剂对骨髓瘤细胞的抑制不如万珂？ 自体移植后联合免疫治疗 自体移植后的早期阶段使用抗PD-1抗体耐受性良好 自体移植后应用抗PD1抗体使肿瘤反应性淋巴细胞扩增效应持续6月之久 自体移植后，抗PD1抗体与肿瘤疫苗联用有希望获得更好的疗效 目前正在招募患者，以研究自体DC/MM融合疫苗与抗PD1抗体联合应用的疗效（每次使用抗PD1抗体前1周使用自体DC/MM融合疫苗） Avigan et al, 2014 进一步研究免疫治疗 开发靶向调节蛋白降解的药物 新靶向治疗和联合用药方案的发现 运用基因组方法实现准确分型及个体化治疗 骨髓瘤将成为一种慢性病，相当一部分患者能获得持续CR 未来的研究方向 * * Slide 6. Historical Perspective: MM The first successful use of chemotherapy for MM was reported in 1958; a racemic mixture of D- and L-phenylalanine called “sarcolysine” was used. Tests of the 2 isomers demonstrated that the L-isomer was responsible for the anti-myeloma activity. In 1962, Bergsagel et al from SWOG reported that L-phenylalanine mustard (melphalan) produced remissions in about one-third of patients with MM In 1967, Salmon et al reported that high doses of glucocorticoids could induce remissions in patients with refractory or relapsing MM. Subsequently, combination therapy with melphalan and prednisone was extensively studied, and in 1972 Alexanian et al reported on its efficacy In 1983, McElwain and Powles reported that high-dose melphalan was effective for patients with MM and plasma cell leukemia. In 1984, Barlogie et al reported on the successful treatment of advanced MM with VAD. In 1986, the group described the efficacy of high-dose glucocorticosteroid therapy for the treatment of patients with resistant disease In 1996, Berenson et al described the efficacy of bisphosphonate pamidronate in reducing skeletal events in patients with advanced MM High-dose therapy with autologous stem cell support and thalidomide and arsenic trioxide treatment for patients with relapsed and refractory disease were introduced in 1999 At the beginning of the 21st century, other major advances included MAbs, proteosome inhibitors, and other IMiDs for treating patients with MM Barlogie B et al. N Engl J Med. 1984;310:1353 Berenson JR et al. N Engl J Med. 1996;334:488 Alexanian R et al. Ann Intern Med. 1986