Bergsagel P Leif
From the Mayo Clinic in Arizona, Scottsdale, AZ.
Am Soc Clin Oncol Educ Book. 2014:199-203. doi: 10.14694/EdBook_AM.2014.34.199.
The celebration of the 50th anniversary of the founding of the American Society of Clinical Oncology provides the occasion to review the progress that has been made in the biology and treatment of multiple myeloma. With the advent of melphalan and cyclophosphamide in the early 1960s the median survival of patients with multiple myeloma more than doubled from 10 months to approximately 24 months. Throughout multiple clinical trials in the 1970s and 1980s, melphalan and prednisone remained the gold standard, with a 3-year survival of 42%. The use of high-dose melphalan with autologous hematopoietic stem cell support provided an incremental advance in the 1990s. The outlook for patients was dramatically improved in the 2000s with the introduction of thalidomide analogs and proteasome inhibitors, so that the 3-year survival of patients treated in 2008 with melphalan and prednisone had increased to 66%. The 2010s are dominated by studying the optimal combination, sequence, and duration of therapies. These clinical advances have occurred along with our evolving understanding of the molecular pathogenesis of myeloma. Myeloma can be divided into two main groups: hyperdiploid, with multiple trisomies of odd-numbered chromosomes, and nonhyperdiploid, with recurrent immunoglobulin heavy chain gene translocations. Disease progression is associated with rearrangements of MYC, the most common mutation in myeloma, present in nearly half of patients. Genomic studies have highlighted marked subclonal heterogeneity that poses one of the main challenges to successful control of the disease. This problem will be addressed in future studies in the 2020s, which will include a focus on immunologic approaches such as monoclonal antibodies, checkpoint inhibitors, engineered T-cells, and novel immunomodulators.
美国临床肿瘤学会成立50周年的庆典为回顾多发性骨髓瘤生物学和治疗方面所取得的进展提供了契机。随着20世纪60年代初美法仑和环磷酰胺的问世，多发性骨髓瘤患者的中位生存期从10个月增加了一倍多，达到约24个月。在20世纪70年代和80年代的多项临床试验中，美法仑和泼尼松一直是金标准，3年生存率为42%。20世纪90年代，高剂量美法仑联合自体造血干细胞支持取得了进一步进展。21世纪初，沙利度胺类似物和蛋白酶体抑制剂的引入使患者的前景得到了显著改善，以至于2008年接受美法仑和泼尼松治疗的患者3年生存率提高到了66%。21世纪10年代主要致力于研究治疗的最佳组合、顺序和持续时间。这些临床进展是在我们对骨髓瘤分子发病机制的认识不断演变的过程中取得的。骨髓瘤可分为两个主要组：超二倍体组，具有多条奇数染色体三体；非超二倍体组，具有复发性免疫球蛋白重链基因易位。疾病进展与MYC重排有关，MYC是骨髓瘤中最常见的突变，近半数患者存在该突变。基因组研究突出了显著的亚克隆异质性，这是成功控制该疾病的主要挑战之一。21世纪20年代的未来研究将解决这个问题，这些研究将包括专注于免疫疗法，如单克隆抗体、检查点抑制剂、工程化T细胞和新型免疫调节剂。
