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：

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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。