Department of Hematology, Niguarda Cancer Center, Niguarda Hospital, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy.
Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Health Qual Life Outcomes. 2019 Nov 15;17(1):173. doi: 10.1186/s12955-019-1232-8.
In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δ inhibitor, + bendamustine/rituximab improved progression-free survival (PFS) and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study.
From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis.
In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo.
Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms.
Clinicaltrials.gov NCT01569295. Registered April 3, 2012.
在一项 3 期随机、双盲、安慰剂对照试验中，磷酸肌醇-3 激酶 δ 抑制剂idelalisib 联合苯达莫司汀/利妥昔单抗治疗复发/难治性慢性淋巴细胞白血病（R/R CLL）患者，改善了无进展生存期（PFS）和总生存期（OS）。此处我们报告了该研究中与健康相关的生活质量（HRQL）分析结果。
2012 年 6 月 15 日至 2014 年 8 月 21 日，共纳入 416 例 R/R CLL 患者；207 例患者被随机分配至 idelalisib 组，209 例患者被随机分配至安慰剂组。在随机接受苯达莫司汀/利妥昔单抗联合口服 idelalisib 150mg 每日 2 次或安慰剂的 416 例患者中，在基线时以及研究的盲法部分，使用功能性评估癌症治疗-白血病（FACT-Leu）和欧洲五维健康量表（EQ-5D）视觉模拟量表（VAS）问卷评估 HRQL。评估在预定的患者就诊时进行；治疗开始后最初 6 个月每 4 周进行一次，然后接下来 6 个月每 8 周进行一次，此后每 12 周进行一次，直到研究结束。使用混合效应模型，通过包括治疗、时间和治疗-时间交互以及分层因素作为固定效应，估计从基线的最小二乘均数变化。采用 Kaplan-Meier 分析评估首次症状改善的时间。
在混合效应模型分析中，idelalisib+苯达莫司汀/利妥昔单抗治疗可使白血病相关症状从基线开始得到有临床意义的改善。此外，Kaplan-Meier 分析表明，与未接受 idelalisib 的患者相比，接受 idelalisib 治疗的患者症状改善的比例更高，且改善时间更短。与安慰剂相比，idelalisib 可改善患者的物理和社会/家庭 FACT-Leu 子量表评分以及 EQ-VAS 自评健康状况，但差异无统计学意义。功能性和情感 FACT-Leu 子量表评分与安慰剂相似。
除了改善 PFS 和 OS 外，idelalisib 联合苯达莫司汀/利妥昔单抗治疗对 R/R CLL 患者的 HRQL 具有中性至有益的影响，特别是可减轻白血病特异性疾病症状。
Clinicaltrials.gov NCT01569295。于 2012 年 4 月 3 日注册。
