Final Analysis of the Daliah Trial: A Randomized Phase III Trial of Interferon-α Versus Hydroxyurea in Patients with MPN

医学 内科学 骨髓纤维化 原发性血小板增多症 胃肠病学 随机对照试验 真性红细胞增多症 精确检验 骨髓
作者
Trine Alma Knudsen,Dennis Lund Hansen,Lukas Frans Ocias,Ole J. Bjerrum,Mette Brabrand,Sarah Friis Christensen,Christina Schjellerup Eickhardt‐Dalbøge,Christina Ellervik,Daniel El Fassi,Mikael Frederiksen,Lasse Kjær,Thomas Kristensen,Torben A. Kruse,Morten Kranker Larsen,Torben Mourits‐Andersen,Sören Möller,Ulrik Malthe Overgaard,Marianne Tang Severinsen,Vibe Skov,Anders Lindholm Sørensen,Jesper Stentoft,Jørn Starklint,Karin de Stricker,Mads Thomassen,Thomas Stauffer Larsen,Hans Carl Hasselbalch
出处
期刊:Blood [Elsevier BV]
卷期号:142 (Supplement 1): 746-746 被引量:2
标识
DOI:10.1182/blood-2023-173127
摘要

Background: Hydroxyurea (HU) is the most commonly used first-line cytoreductive treatment option for patients with myeloproliferative neoplasms (MPN) worldwide. However, increasing evidence on the efficacy and safety of pegylated interferon-alpha2 (IFNα) is emerging, and optimal first-line treatment is to be established. Aims: To compare the efficacy and safety of HU vs. low-dose IFNα in patients with MPN over five years. Methods: DALIAH (NCT01387763) was a randomized phase III trial of HU vs. IFNα in newly diagnosed or untreated patients with MPN (essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic myelofibrosis (PreMF), and primary myelofibrosis (PMF)). Patients > age 60 were randomized (1:1:1) to HU, IFNα-2a, or IFNα-2b whereas patients ≤ age 60 were randomized to IFNα-2a or IFNα-2b. The primary outcome was the JAK2V617F molecular response (MR) rate at 18, 36, and 60 months per 2009 European LeukemiaNetwork (ELN) (ET, PV, PreMF) or 2005 European Myelofibrosis Network (EUMNET) (PMF) criteria. Secondary outcomes included the complete clinicohematologic response (CHR) rate at 12 months. The JAK2V617F allele burden was measured using quantitative polymerase chain reaction (qPCR) on peripheral blood (assay sensitivity: 0.1%). Primary and secondary outcomes were compared between groups (HU vs. IFNα or HU vs. IFNα > 60 years) using Fisher's exact test (categorical variables) or Wilcoxon rank-sum test (continuous variables). Paired comparisons (within groups) were made using Wilcoxon signed-rank test. Serial JAK2V617F measurements were compared by unadjusted mixed-effects linear regression analysis. Results: We included 203 patients (ET: 73 (36%), PV: 89 (44%), PreMF: 16 (8%), and PMF: 25 (12%)) in the modified intention-to-treat (ITT) population. Baseline characteristics were well balanced except for median age (HU: 68 years vs. IFNα: 59 years, p<0.0001) ( Table 1). The MR rate by ITT analysis was similar between HU and IFNα (18 months: 19% vs. 21%, p=1.00; 36 months: 19% vs. 26%, p=0.64; 60 months: 23% vs. 24%, p=1.00) (Figure 1A). However, the JAK2V617F allele burden was significantly lower in the IFNα group at month 36 and beyond (Figure 1B) and the absolute median (IQR) change in JAK2V617F allele burden (baseline to 60 months) was greater with IFNα (-20% (-9;-49) vs. -7% (3;-15), p=0.0053) (Figure 1C). Two patients (IFNα: n=2) were in complete molecular remission (undetectable JAK2V617F) at 60 months. The CHR rate by ITT analysis was higher with HU at 18 months (58% vs. 38%, p=0.03) but similar at all other time points (12 months: 50% vs. 36%, p=0.21; 60 months: 24% vs. 22%, p=0.83) ( Figure 1D). A post hoc subgroup analysis comparing HU with IFNα > age 60 showed comparable efficacy results. Among patients remaining on treatment (per-protocol analysis), the MR and CHR rates were superior in the IFNα group compared to the HU group at 36 months and beyond. The MR and CHR rates (HU vs. IFNα) by per-protocol analysis were: MR at 36 months: 23% vs. 56%, p=0.01; MR at 48 months: 27% vs. 59%, p=0.02; MR at 60 months: 35% vs. 67%, p=0.03; CHR at 36 months: 33% vs. 67%, p=0.002; CHR at 60 months: 38% vs. 62%, p=0.05. Overall treatment discontinuation at 60 months was 60% (HU: 37% vs. IFNα: 65%, p=0.0019). The most common cause of treatment discontinuation was adverse events (HU: 6/38 (16%); IFNα: 71/165 (43%)). Adverse events ≥ grade 3 occurred in 46% (HU: 58% vs. IFNα: 45%, p=0.15). Nineteen major thrombotic events were reported in 16 patients (HU: 4 events in 4 patients; IFNα>60: 12 events in 10 patients; IFNα≤60: 3 events in 2 patients), corresponding to an incidence rate of 2.6 per 100 person-years for HU and 3.4 per 100 person-years for IFNα (IFNα>60: 6.2; IFNα≤60: 1.2). None of the patients transformed into secondary acute myeloid leukemia. Five patients died during follow-up (HU: 2; IFNα: 3). Bone marrow histologic remission rates at 36 and 60 months will be presented at the meeting. Conclusion: ITT analysis detected no significant difference in the MR or CHR rates between HU and IFNα with long-term treatment (5 years) among patients with MPN, reflecting a higher treatment discontinuation rate in the IFNα group (65%). Thus, using the per-protocol principle, the MR and CHR rates were superior in the IFNα group at 36 months and beyond.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
3秒前
北城完成签到 ,获得积分10
5秒前
量子星尘发布了新的文献求助10
5秒前
8秒前
爱听歌电灯胆完成签到 ,获得积分10
8秒前
不爱吃西葫芦完成签到 ,获得积分10
9秒前
申燕婷完成签到 ,获得积分10
10秒前
橙子完成签到 ,获得积分10
12秒前
ruochenzu发布了新的文献求助10
12秒前
fusheng完成签到 ,获得积分10
21秒前
浮生完成签到 ,获得积分10
26秒前
xinjie完成签到,获得积分10
28秒前
Will完成签到,获得积分10
33秒前
cuddly完成签到 ,获得积分10
34秒前
掉头发的小白完成签到,获得积分10
35秒前
不想看文献完成签到 ,获得积分10
38秒前
39秒前
当女遇到乔完成签到 ,获得积分10
39秒前
独行者完成签到,获得积分10
40秒前
眼睛大的电脑完成签到,获得积分10
40秒前
42秒前
敏敏发布了新的文献求助10
43秒前
木木完成签到 ,获得积分10
44秒前
量子星尘发布了新的文献求助10
44秒前
JamesPei应助科研通管家采纳,获得10
45秒前
彭于晏应助科研通管家采纳,获得10
45秒前
如意2023完成签到 ,获得积分10
45秒前
fomo完成签到,获得积分10
49秒前
nagi发布了新的文献求助10
52秒前
jfeng完成签到,获得积分10
54秒前
JN完成签到,获得积分10
1分钟前
忐忑的书桃完成签到 ,获得积分10
1分钟前
qaplay完成签到 ,获得积分0
1分钟前
友好语风完成签到,获得积分10
1分钟前
CLTTTt完成签到,获得积分10
1分钟前
yk完成签到,获得积分10
1分钟前
甜美的初蓝完成签到 ,获得积分10
1分钟前
早安完成签到 ,获得积分10
1分钟前
初昀杭完成签到 ,获得积分10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022