Buske Christian, Sadullah Shalal, Kastritis Efstathios, Tedeschi Alessandra, García-Sanz Ramón, Bolkun Lukasz, Leleu Xavier, Willenbacher Wolfgang, Hájek Roman, Minnema Monique C, Cheng Mei, Bilotti Elizabeth, Graef Thorsten, Dimopoulos Meletios A
Comprehensive Cancer Center Ulm, University Hospital of Ulm, Ulm, Germany.
James Paget University Hospital, Norfolk, UK.
Lancet Haematol. 2018 Jul;5(7):e299-e309. doi: 10.1016/S2352-3026(18)30087-5.
Treatment options for Waldenström's macroglobulinaemia are heterogeneous, and no well established treatment standards exist. Although guidelines from the Eighth International Workshop on Waldenstrom's Macroglobulinemia were published in 2016, inconsistent awareness and budget constraints have prevented their widespread implementation, and real-life treatment patterns might differ across health-care systems. We aimed to generate information about treatment and outcome patterns for patients with Waldenström's macroglobulinaemia outside of clinical trials.
In this large, observational, retrospective chart review, academic and community physicians in ten European countries were invited to retrospectively complete electronic records for patients with symptomatic Waldenström's macroglobulinaemia who had begun treatment after Jan 1, 2000, and before Jan 1, 2014, and had available clinical and biological data. The primary endpoints were reasons for treatment initiation, treatment choices, progression-free survival, and overall survival. We assessed the variables that affected choice of front-line therapy, progression-free survival, and overall survival in multivariate analyses.
Electronic records were reviewed for 454 eligible patients. The most frequent reasons for starting front-line treatment were anaemia (in 328 [72%] patients) and constitutional symptoms (in 264 [58%] patients). Choice of therapy varied between front-line, second-line, and third-line approaches; age; and type of institution. In the front-line setting, 193 (43%) of 454 patients received monotherapy, 164 (36%) received chemoimmunotherapy, and 95 (21%) received other combination regimens (data on front-line treatment were missing for one patient, and another patient received only steroids). After front-line treatment, median progression-free survival was 29 months (95% CI 25-31), median overall survival was not reached (not reached-not reached), and 10-year overall survival was 69% (62-74). In multivariate analyses, patients who were high risk according to the International Prognostic Scoring System for Waldenström Macroglobulinemia had significantly worse progression-free survival and overall survival than did those who were low risk. Additionally, progression-free survival was shortened in patients treated with monotherapy compared with those treated with chemoimmunotherapy or other combination therapies and in those treated at an academic institution compared with those treated in the community. Constitutional symptoms (excluding fatigue) were associated with worsened overall survival.
This large observational dataset should inform and help set guidelines, and improve understanding of treatment practices and outcomes, for European patients with Waldenström's macroglobulinaemia.
Pharmacyclics LLC (an AbbVie company).
华氏巨球蛋白血症的治疗方案多种多样，且尚无成熟的治疗标准。尽管2016年发布了第八届华氏巨球蛋白血症国际研讨会的指南，但认识不一致和预算限制阻碍了其广泛实施，不同医疗体系的实际治疗模式可能存在差异。我们旨在获取临床试验之外华氏巨球蛋白血症患者的治疗及预后模式信息。
在这项大型观察性回顾性病历审查中，邀请了十个欧洲国家的学术和社区医生回顾性地完成2000年1月1日至2014年1月1日期间开始治疗且有可用临床和生物学数据的有症状华氏巨球蛋白血症患者的电子记录。主要终点为治疗起始原因、治疗选择、无进展生存期和总生存期。我们在多变量分析中评估了影响一线治疗选择、无进展生存期和总生存期的变量。
对454例符合条件的患者的电子记录进行了审查。开始一线治疗最常见的原因是贫血（328例[72%]患者）和全身症状（264例[58%]患者）。治疗选择在一线、二线和三线治疗方法、年龄以及机构类型之间存在差异。在一线治疗中，454例患者中有193例（43%）接受单药治疗，164例（36%）接受化疗免疫治疗，95例（21%）接受其他联合方案（1例患者一线治疗数据缺失，另1例患者仅接受了类固醇治疗）。一线治疗后，中位无进展生存期为29个月（95%CI 25 - 31），中位总生存期未达到（未达到 - 未达到），10年总生存率为69%（62 - 74）。在多变量分析中，根据华氏巨球蛋白血症国际预后评分系统为高危的患者，其无进展生存期和总生存期显著差于低危患者。此外，与接受化疗免疫治疗或其他联合治疗的患者相比，接受单药治疗的患者无进展生存期缩短；与在社区治疗的患者相比，在学术机构治疗的患者无进展生存期缩短。全身症状（不包括疲劳）与总生存期恶化相关。
这个大型观察数据集应为欧洲华氏巨球蛋白血症患者提供信息并有助于制定指南，同时增进对治疗实践和预后的理解。
Pharmacyclics LLC（艾伯维公司）。
