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Succeeding in Breaking the R-CHOP Ceiling in DLBCL: Learning From Negative Trials
Journal of Clinical Oncology ( IF 42.1 ) Pub Date : 2017-09-19 , DOI: 10.1200/jco.2017.74.7360
Andre Goy 1
Affiliation  

The introduction of anthracyclines into the first-generation regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in 1976 resulted in a 10-year overall survival of around 20%.1 Despite being promising in phase II testing, more complex second- and third-generation regimens did not supersede CHOP in a large phase III trial.2 A decade later, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab became the first improvement over CHOP,3 initially shown in patients older than age 60 years, but rapidly confirmed for all patients with diffuse large B-cell lymphoma (DLBCL), setting a new standard that is still valid today. With six cycles of rituximab plus CHOP (R-CHOP) given once every 21 days, more than half of patients can be cured, and in those who are event-free at 24 months, the subsequent survival is equivalent to that of the age- and sex-matched general population.4 However, about 10% to 20% of patients do not respond to R-CHOP induction (ie, primary refractory), and 30% to 40% relapse after achieving complete remission (CR). Overall, 80% of all chemoimmunotherapy failures occur early (within 12 to 18 months of diagnosis), and patients then often experience a poor outcome,5 even with high-dose therapy followed by autologous stem-cell transplantation.6 These observations have formed the basis of numerous attempts to improve on R-CHOP, which have generally been unsuccessful thus far.

中文翻译:

成功打破DLBCL中的R-CHOP上限:从否定性试验中学习

1976年将蒽环类药物引入环磷酰胺,阿霉素,长春新碱和泼尼松(CHOP)的第一代治疗方案后,其10年总生存率约为20%。1尽管在II期试验中很有希望,但更复杂的第二代和第三代方案在大型III期试验中并未取代CHOP。2十年后,抗CD20单克隆抗体(mAb)利妥昔单抗的添加成为CHOP的第一个改进,3最初显示于60岁以上的患者中,但很快被所有弥漫性大B细胞淋巴瘤(DLBCL)患者确认,并设定了今天仍然有效的新标准。每21天进行一次六个周期的利妥昔单抗联合CHOP(R-CHOP)治疗,可以治愈一半以上的患者,对于24个月无事件的患者,其随后的存活率与和性别匹配的普通人群。4然而,约10%至20%的患者对R-CHOP诱导(即原发性难治性)无反应,并且在达到完全缓解(CR)后复发30%至40%。总体而言,所有化学免疫疗法失败的80%都是较早发生(在诊断后12到18个月内),然后患者通常会出现较差的预后,[ 5]即使采用大剂量疗法,然后进行自体干细胞移植。6这些观察结果构成了许多尝试改进R-CHOP的基础,到目前为止,这些尝试通常都没有成功。
更新日期:2017-09-20
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