Kühnl A, Cunningham D, Counsell N, Hawkes E A, Qian W, Smith P, Chadwick N, Lawrie A, Mouncey P, Jack A, Pocock C, Ardeshna K M, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson P W, Gambell J, Rosenwald A, Ott G, Horn H, Ziepert M, Pfreundschuh M, Linch D
Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey.
Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK.
Ann Oncol. 2017 Jul 1;28(7):1540-1546. doi: 10.1093/annonc/mdx128.
There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up.
Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials.
Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors.
Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches.
ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).
对于老年弥漫性大B细胞淋巴瘤（DLBCL）患者，每2周或3周给予R-CHOP方案作为一线治疗的首选方案，目前仍存在争议。英国国家癌症研究所（NCRI）的R-CHOP14v21随机3期试验未显示新诊断的19-88岁DLBCL患者中，R-CHOP-14和R-CHOP-21在疗效上存在差异，但迄今为止，老年患者的数据尚未详细报道。在此，我们对R-CHOP14v21试验中年龄≥60岁的患者进行亚组分析，并延长随访时间。
本亚组分析纳入了604例年龄≥60岁的R-CHOP14v21患者，中位随访时间为77.7个月。为评估MYC重排（MYC-R）和双打击淋巴瘤（DHL）对老年患者预后的影响，我们对R-CHOP14v21（N = 217）和RICOVER-60（N = 204）试验中具有可用分子数据的病例进行了联合分析。
老年DLBCL患者接受了高剂量强度治疗，所有药物的中位总剂量≥98%。除R-CHOP-21组的≥3级中性粒细胞减少症更多（P < 0.0001）和≥3级血小板减少症更少（P = 0.05）外，两组的毒性反应相似。老年患者群体的5年总生存率（OS）良好，为69%（95%CI：65-73）。我们未发现任何对任一治疗方案有不同反应的患者亚组。在包括国际预后指数（IPI）的个体因素、性别、肿块大小、β2微球蛋白（B2M）和白蛋白水平的多变量分析中，只有年龄和B2M对OS具有独立预后意义。分子分析表明，在联合试验队列中，MYC-R（HR = 1.96；95%CI：1.22-3.16；P = 0.01）和DHL（HR = 2.21；95%CI：1.18-4.11；P = 0.01）对OS有显著影响，且独立于其他预后因素。
我们的数据支持两种R-CHOP应用形式在老年DLBCL患者中的等效性。老年MYC-R和DHL患者预后较差，应考虑采用替代治疗方法。
ISCRTN 16017947（R-CHOP14v21）；NCT00052936（RICOVER-60）。
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