Quality of life independently predicts overall survival in myelofibrosis: Key insights from the COntrolled MyeloFibrosis Study with ORal Janus kinase inhibitor Treatment (COMFORT)‐I study
Quality of life independently predicts overall survival in myelofibrosis: Key insights from the COntrolled MyeloFibrosis Study with ORal Janus kinase inhibitor Treatment (COMFORT)‐I study
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生活质量独立预测骨髓纤维化患者的总体生存率：使用 ORal Janus 激酶抑制剂治疗的控制性骨髓纤维化研究 (COMFORT) 的主要见解 –I 研究
DOI：
10.1111/bjh.18329
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发表时间：
2022
影响因子：
6.5
通讯作者：
Palmer, Jeanne M.
中科院分区：
文献类型：
--
作者：
Kosiorek, Heidi E.;Scherber, Robyn M.;Geyer, Holly L.;Verstovsek, Srdan;Langlais, Blake T.;Mazza, Gina L.;Gotlib, Jason;Gupta, Vikas;Padrnos, Leslie J.;Palmer, Jeanne M.
患者报告的结果（PRO）对于生存预测具有相当大的价值，通常包括生活质量（QOL）和症状测量。最近对 44 项 II 期或 III 期随机临床试验进行的荟萃分析发现，在控制体能状态 (PS)、肿瘤分期和血清标志物等相关临床变量后，93% 的研究中总生存期 (OS) 与至少一个基线 PRO 域相关。 1 在对 138 项研究进行的系统评价中，87% 的研究报告至少有一项 PRO 对 OS 预测具有重要意义。 2 骨髓纤维化 (MF) 与脾肿大、血细胞减少和高症状负担有关。 3 在两项 III 期临床试验中，鲁索替尼与脾肿大、症状负担、生活质量测量和 OS 的改善相关。 4-6 在 MF 中，症状非常普遍，并被纳入反应标准和临床试验评估中。骨髓增生性肿瘤 (MPN) 患者的主要症状还与生活质量下降有关。 7 本分析的目的是评估参加 ORal Janus 激酶 (JAK) 抑制剂治疗的控制性骨髓纤维化研究 (COMFORT)-I 试验的 MF 患者基线 QOL 与 OS 的预后相关性。鲁索替尼与安慰剂治疗中危 2 级或高危 MF 患者的 COMFORT-I 试验数据（ClinicalTrials.gov 标识符：NCT00952289）从 Incyte© 获得，用于独立分析。考虑用于预测 OS 的 4 个 PRO 变量包括总症状评分 (TSS)、功能分量表、整体健康状况 (GHS)/QOL 和疲劳。临床因素包括年龄、性别、国际预后评分系统（IPSS）风险评分、PS和治疗组（有关措施的详细信息，请参阅补充附录）。 OS 分析包括意向治疗方法和交叉时审查安慰剂患者。在控制临床因素时，使用多变量 Cox 比例风险模型来检查症状和 GHS/QOL 基线测量的影响。由于安慰剂组中大量交叉使用鲁索替尼，因此还评估了保留等级的结构失效时间方法（RPSFT）。 COMFORT-I 研究招募了 309 名患者（155 名鲁索替尼，154 名安慰剂）； 111 名（72%）安慰剂患者最终转用鲁索替尼。 4 296 名患者的基线 GHS/QOL 可用，并且治疗组之间没有差异（表 S1）。 GHS/QOL 评分较低的患者的症状负担和疲劳显着较高（表 S2）。此外，GHS/QOL 中值分割分位数组的 IPSS 风险和欧洲癌症研究与治疗组织 (EORTC) 领域存在显着差异。 PS 为 0 的患者的平均 (SD) GHS/QOL 为 59.6 (22.0)，PS 为 1 的患者为 51.7 (22.1)，PS 为 2/3 的患者为 43.8 (20.6)（F= 7.97，p < 0.001）。中间 2 评分的平均 (SD) GHS/QOL 为 55.8 (22.3)，而高风险评分的患者为 50.9 (22.5) (p= 0.07)，中间 2 评分的 TSS 为 19.8 (11.1)，而高风险评分的平均 (SD) GHS/QOL 为 16.1 (11.4) (p= 0.005)。 TSS 与 GHS/QOL 呈负相关（r=− 0.36；p< 0.001）；症状项目相关性范围从盗汗的 r=− 0.14 到骨/肌肉疼痛的 r=− 0.38（表 S3）。长期分析报告的 OS 结果有利于鲁索替尼（风险比 [HR] 0.69，95% 置信区间 [CI] 0.50–0.96；p= 0.03）。 8 在意向治疗分析（HR 0.69，95% CI 0.49–0.96；p= 0.03）和交叉时对安慰剂患者进行审查时（HR 0.57，95% CI 0.37–0.88；p …
Patient-reported outcomes (PROs) have considerable value for survival prediction, and generally include both quality of life (QOL) and symptom measures. A recent metaanalysis of 44 phase II or III randomised clinical trials found that overall survival (OS) was associated with at least one baseline PRO domain in 93% of studies, after controlling for pertinent clinical variables like performance status (PS), tumour staging and serum markers. 1 In a systematic review of 138 studies, 87% reported at least one PRO being significant for OS prognostication. 2 Myelofibrosis (MF) is associated with splenomegaly, cytopenias and a high symptom burden. 3 In two phase III clinical trials, ruxolitinib was associated with improvements in splenomegaly, symptom burden, QOL measures and OS. 4–6 In MF, symptoms have been shown to be highly prevalent and are incorporated into response criteria and clinical trials assessments. Key symptoms are also associated with decreased QOL in patients with myeloproliferative neoplasms (MPNs). 7 The objective of this analysis was to evaluate the prognostic relevance of baseline QOL on OS among patients with MF enrolled in the COntrolled MyeloFibrosis Study with ORal Janus kinase (JAK) inhibitor Treatment (COMFORT)-I trial. Data from the COMFORT-I trial of ruxolitinib versus placebo for patients with intermediate-2 or high-risk MF (ClinicalTrials. gov Identifier: NCT00952289) was obtained from Incyte© for independent analysis. 4 PRO variables considered for prognostication of OS included total symptom score (TSS), functional subscales, global health status (GHS)/QOL, and fatigue. Clinical factors included age, sex, International Prognostic Scoring System (IPSS) risk score, PS and treatment arm (see Supplementary Appendix for details on measures). Analysis of OS included both the intention-totreat method and censoring placebo patients at the time of crossover. A multivariable Cox proportional hazards model was used to examine the effect of symptoms and GHS/QOL baseline measures when controlling for clinical factors. Due to the substantial amount of crossover to ruxolitinib in the placebo arm, the rank-preserving structural failure time method (RPSFT) was also evaluated. The COMFORT-I study enrolled 309 patients (155 ruxolitinib, 154 placebo); 111 (72%) placebo patients ultimately crossed over to ruxolitinib. 4 Baseline GHS/QOL was available in 296 patients and did not differ by treatment arm (Table S1). Symptom burden and fatigue were significantly higher in patients with lower GHS/QOL scores (Table S2). In addition, IPSS risk and European Organisation for the Research and Treatment of Cancer (EORTC) domains differed significantly by GHS/QOL median-split quantile groups. The mean (SD) GHS/QOL was 59.6 (22.0) in patients with a PS of 0, 51.7 (22.1) in patients with a PS of 1 and 43.8 (20.6) in patients with a PS of 2/3 (F= 7.97, p< 0.001). The mean (SD) GHS/QOL was 55.8 (22.3) for intermediate-2 versus 50.9 (22.5) for high-risk patients (p= 0.07) and TSS was 19.8 (11.1) for intermediate-2 versus 16.1 (11.4) for highrisk score (p= 0.005). TSS was inversely correlated with GHS/QOL (r=− 0.36; p< 0.001); symptom item correlations ranged from r=− 0.14 for night sweats to r=− 0.38 for bone/muscle pain (Table S3).Long-term analysis reported OS results favouring ruxolitinib (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50–0.96; p= 0.03). 8 Higher GHS/QOL score at baseline (> median vs.≤ median) was associated with increased OS on both intention-to-treat analysis (HR 0.69, 95% CI 0.49–0.96; p= 0.03) and when patients on placebo were censored at crossover (HR 0.57, 95% CI 0.37–0.88; p …
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影响因子：
45.3
作者：
Emanuel, Robyn M.;Dueck, Amylou C.;Mesa, Ruben A.
通讯作者：
Mesa, Ruben A.
影响因子：
7.5
作者：
Stojkov I;Conrads-Frank A;Rochau U;Koinig KA;Arvandi M;Puntscher S;van Marrewijk C;Fenaux P;Symeonidis A;Chermat F;Garelius H;Bowen D;Mittelman M;Mora E;de Witte T;Efficace F;Siebert U;Stauder R
通讯作者：
Stauder R
影响因子：
2.6
作者：
Langlais BT;Geyer H;Scherber R;Mesa RA;Dueck AC
通讯作者：
Dueck AC
影响因子：
12.8
作者：
Mannelli, Francesco;Bencini, Sara;Coltro, Giacomo;Loscocco, Giuseppe G.;Peruzzi, Benedetta;Rotunno, Giada;Maccari, Chiara;Gesullo, Francesca;Borella, Miriam;Paoli, Chiara;Caporale, Roberto;Mannarelli, Carmela;Annunziato, Francesco;Guglielmelli, Paola;Vannucchi, Alessandro M.
通讯作者：
Vannucchi, Alessandro M.
最近与健康相关的生活质量（但没有变化）预测的死亡率和医疗保健利用率：与健康相关的生活质量是死亡率和利用率的预测因子。
影响因子：
7.2
作者：
J. Singh;David B. Nelson;K. Nichol
通讯作者：
K. Nichol