Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany.
Department of Hematology and Lymphoma Study Association (LYSA), Hopital Le Bocage, CHU Dijon, Dijon, France.
Ann Oncol. 2017 Jun 1;28(6):1352-1358. doi: 10.1093/annonc/mdx072.
Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT.
In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II).
In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [<partial remission by computed tomography (CT)] as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; P < 0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; P < 0.0001).
Based on this large study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials.
GHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.
新型药物正在改变复发或难治性霍奇金淋巴瘤（HL）的治疗方法。然而，在符合条件的患者中，大剂量化疗和自体干细胞移植（ASCT）仍被视为标准治疗。为了确定最能从新型治疗方法中受益的患者，我们研究了一组与 ASCT 后生存相关的综合风险因素（RFs）。
在这项多中心预后多变量建模研究中，我们回顾性评估了来自 9 项前瞻性试验的 23 个潜在 RFs，采用多变量 Cox 比例风险回归分析（第 I 部分）。然后，在一个独立的临床样本中验证了由此产生的预后评分（第 II 部分）。
在第 I 部分中，我们纳入了 1993 年至 2013 年间接受治疗的 656 例复发/难治性 HL 患者，ASCT 后中位随访时间为 60 个月。大多数潜在的 RFs 对无进展生存期（PFS）有显著影响，风险比（HR）范围为 1.39 至 2.22。多变量分析确定了 IV 期疾病、复发时间≤3 个月、ECOG 表现状态≥1、肿块≥5cm 和挽救性化疗无应答（按 CT 评估为不完全缓解）是 PFS 的显著且非冗余 RFs。由这些同样权重的 RFs 组成的风险评分对 PFS 具有显著的预后意义（每增加一个 RF，HR=1.67；P<0.0001）。在另一个独立的 389 例患者样本中进行验证，该样本在不同临床环境中接受治疗，通过功能成像评估挽救治疗的反应，而不是 CT，这验证了风险组的出色区分度和 ASCT 后 PFS 和总生存期（OS）的显著预测能力（HR=1.70 和 HR=1.63；P<0.0001）。
基于这项大型研究（n=1045），可通过 5 个易于获得的临床 RFs 实现 ASCT 后 HL 患者的精确和有效风险预测。因此，该预后评分可在临床实践和未来试验中可靠地对患者进行分层，以采用创新的治疗方法。
GHSG HD10 NCT00265018、HD11 NCT00264953、HD12 NCT00265031、HD13 ISRCTN63474366、HD14 ISRCTN04761296、HD15 ISRCTN32443041 和 HDR2 NCT00025636。
