既往未经治疗的晚期经典型霍奇金淋巴瘤老年患者(年龄≥60岁):来自III期ECHELON-1研究的详细分析
Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study.
作者信息
Evens Andrew M, Connors Joseph M, Younes Anas, Ansell Stephen M, Kim Won Seog, Radford John, Feldman Tatyana, Tuscano Joseph, Savage Kerry J, Oki Yasuhiro, Grigg Andrew, Pocock Christopher, Dlugosz-Danecka Monika, Fenton Keenan, Forero-Torres Andres, Liu Rachael, Jolin Hina, Gautam Ashish, Gallamini Andrea
机构信息
Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.
BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology, Vancouver.
出版信息
Haematologica. 2022 May 1;107(5):1086-1094. doi: 10.3324/haematol.2021.278438.
Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs. <60 years) was a pre-specified subgroup analysis; as the ECHELON- 1 study was not powered for these analyses, reported P-values are descriptive. Of 1,334 enrolled patients, 186 (14%) were aged ≥60 years (A+AVD: n=84, ABVD: n=102); results below refer to this age group. Modified progression-free survival per independent review facility was similar in the two arms at 24 months (A+AVD: 70.3% [95% confidence interval (CI): 58.4-79.4], ABVD: 71.4% [95% CI: 60.5-79.8], hazard ratio (HR)=1.00 [95% CI: 0.58-1.72], P=0.993). After a median follow-up of 60.9 months, 5-year progression-free survival per investigator was 67.1% with A+AVD versus 61.6% with ABVD (HR=0.820 [95% CI: 0.494-1.362], P=0.443). Comparing A+AVD versus ABVD, grade 3/4 peripheral neuropathy occurred in 18% versus 3%; any-grade febrile neutropenia in 37% versus 17%; and any-grade pulmonary toxicity in 2% versus 13%, respectively, with three (3%) pulmonary toxicity-related deaths in patients receiving ABVD (none in those receiving A+AVD). Altogether, A+AVD showed overall similar efficacy to ABVD with survival rates in both arms comparing favorably to those of prior series in older patients with advanced-stage classical Hodgkin lymphoma. Compared to ABVD, A+AVD was associated with higher rates of neuropathy and neutropenia, but lower rates of pulmonary-related toxicity. Trials registered at ClinicalTrials.gov identifiers: NCT01712490; EudraCT number: 2011-005450-60.
老年经典型霍奇金淋巴瘤患者需要有效且耐受性良好的治疗方法。我们报告了在大型III期ECHELON-1研究中接受治疗的老年经典型霍奇金淋巴瘤患者的结果,该研究比较了一线使用本妥昔单抗联合多柔比星、长春花碱和达卡巴嗪(A+AVD)与多柔比星、博来霉素、长春花碱和达卡巴嗪(ABVD)的疗效。按独立审查机构评估的改良无进展生存期在老年与年轻患者(年龄≥60岁与<60岁)中的比较是一项预先设定的亚组分析;由于ECHELON-1研究未针对这些分析进行效能计算,所报告的P值仅作描述之用。在1334名入组患者中,186名(14%)年龄≥60岁(A+AVD组:n = 84,ABVD组:n = 102);以下结果指的是这个年龄组。按独立审查机构评估,两组在24个月时的改良无进展生存期相似(A+AVD组:70.3% [95%置信区间(CI):58.4 - 79.4],ABVD组:71.4% [95% CI:60.5 - 79.8],风险比(HR)= 1.00 [95% CI:0.58 - 1.72],P = 0.993)。在中位随访60.9个月后,按研究者评估,A+AVD组的5年无进展生存率为67.1%,ABVD组为61.6%(HR = 0.820 [95% CI:0.494 - 1.362],P = 0.443)。比较A+AVD与ABVD,3/4级周围神经病变的发生率分别为18%和3%;任何级别发热性中性粒细胞减少症的发生率分别为37%和17%;任何级别肺部毒性的发生率分别为2%和13%,接受ABVD治疗的患者中有3例(3%)死于肺部毒性相关原因(接受A+AVD治疗的患者中无死亡病例)。总体而言,A+AVD显示出与ABVD总体疗效相似,两组的生存率与既往晚期老年经典型霍奇金淋巴瘤系列研究的生存率相比更具优势。与ABVD相比,A+AVD与更高的神经病变和中性粒细胞减少症发生率相关,但肺部相关毒性发生率较低。在ClinicalTrials.gov注册的试验标识符:NCT01712490;欧盟临床试验注册号:2011 - 005450 - 60。