清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Radius: A Phase 2 Randomized Trial Investigating Standard of Care ± Midostaurin after Allogeneic Stem Cell Transplant in FLT3 -ITD–Mutated AML

米多司他林 医学 内科学 肿瘤科 移植 Fms样酪氨酸激酶3 癌症研究 帕纳替尼 索拉非尼 胃肠病学 造血干细胞移植 髓系白血病 白血病 无进展生存期 养生
作者
Richard T. Maziarz,Mrinal M. Patnaik,Bart L. Scott,Sanjay R. Mohan,Abhinav Deol,Scott D. Rowley,Dennis Dong Hwan Kim,Kelly Haines,Gaetano Bonifacio,Patrice Rine,Das Purkayastha,Hugo F. Fernandez
出处
期刊:Blood [Elsevier BV]
卷期号:132: 662-662 被引量:49
标识
DOI:10.1182/blood-2018-99-113582
摘要

Abstract Introduction: Midostaurin, a multitargeted tyrosine kinase inhibitor (TKI), plus induction and consolidation chemotherapy followed by single-agent midostaurin maintenance therapy resulted in significant benefits in event-free and overall survival (OS) in adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) compared with placebo (RATIFY study; Stone et al, N Engl J Med, 2017). In RATIFY, patients who received allogeneic hematopoietic stem cell transplant (alloSCT) did not receive midostaurin maintenance. Despite alloSCT providing the highest likelihood of sustained remission, relapse rates remain high (30%-59%; Schiller et al, Biol Blood Marrow Transplant, 2016), especially in patients with FLT3-internal tandem duplication-positive (ITD+) AML. Posttransplant maintenance therapy may improve this outcome. Here, we report the primary results from RADIUS, a randomized, open-label, phase 2 exploratory trial (NCT01883362) that investigated whether the addition of midostaurin to standard of care (SOC) after alloSCT could reduce the risk of relapse in patients with FLT3-ITD+ AML. Methods: Adults (aged 18-70 y) who had undergone myeloablative alloSCT in first complete remission (CR1), had achieved hematologic recovery, and were transfusion independent were eligible. Patients enrolled postengraftment and were randomized to receive SOC with or without midostaurin 50 mg twice daily continuously (4-week cycles) for up to 12 cycles. Study treatment started 28 to 60 days post-alloSCT and patients were followed for ≥24 months post-alloSCT. The primary endpoint was relapse-free survival (RFS) at 18 months post-alloSCT. Secondary endpoints included safety and disease-free survival (DFS), OS, and RFS at 24 months post-alloSCT. The study was not adequately powered to detect a statistical difference between the 2 arms; a sample size of 60 was calculated to detect a 50% reduction in the risk of relapse. Results: 60 patients were randomized (30 per arm). Baseline characteristics were generally balanced between the 2 arms. Overall, 30 patients completed 12 cycles of study treatment (14 with SOC; 16 with midostaurin). The median exposure to midostaurin was 10.5 months (range, 0.2 to 12.0 months) and the median dose intensity was 93 mg/day (range, 15-100 mg/day). Early treatment discontinuations were similar between arms (15 in the SOC arm; 13 in the midostaurin arm), frequently due to adverse events (AEs; 3% vs 23%) and consent withdrawal (20% vs 7%). Among 6 patients who withdrew consent in the SOC arm, 2 did so to pursue other TKI therapies. Midostaurin dose modifications occurred in 19 patients (63%), mostly due to AEs (84%); 1 instance was due to receiving a concomitant CYP3A4 inhibitor. With an estimated 18-month RFS (95% CI) of 76% (54%-88%) in the SOC arm and 89% (69%-96%) in the midostaurin arm, estimated relapse rates were 24% and 11%, respectively, which is a 46% relative reduction in the risk of relapse with the addition of midostaurin (Figure 1). At 18 months, the median RFS was not reached in either arm. Longer follow-up at 24 months (data not yet matured) will be presented, including RFS, OS, and DFS. In the SOC and midostaurin arms, AEs were reported in 87% and 100% of patients, respectively (the most common any-grade AE was vomiting: 23% vs 73%; Figure 2); serious AEs were reported in 57% and 30% of patients, respectively, with diarrhea (7% vs 13%), nausea (10% vs 3%), vomiting (10% vs 3%), and pyrexia (7% vs 7%) being the most common. Overall, 8 patients discontinued midostaurin therapy due to AEs (mostly gastrointestinal related) and 12 died on study (all during the follow-up phase; 8 in the SOC arm and 4 in the midostaurin arm [n=4 vs n=2 due to AML disease progression]). Rates of graft-vs-host disease (GVHD) were generally similar between the SOC and midostaurin arms (overall, 70% vs 73%; acute GVHD, 53% vs 57% [grade 2/3 events: 37% vs 30%; no grade 4 events]; chronic GVHD, 47% vs 37% [most events were mild or moderate; severe events: 1 with SOC and 2 with midostaurin]). Conclusions: Adding midostaurin to SOC reduced the risk of relapse at 18 months post-alloSCT by 46% (vs SOC). The safety profile of single-agent midostaurin was consistent with previous reports; no major safety concerns were identified when adding midostaurin to SOC following alloSCT. These data suggest that midostaurin monotherapy can be safely administered for ≤1 year and may improve outcomes in patients who undergo alloSCT in CR1. Disclosures Maziarz: Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria; Kite Therapeutics: Honoraria; Athersys, Inc.: Patents & Royalties. Scott: Agios: Consultancy; Novartis: Research Funding; Celgene: Consultancy, Research Funding; Alexion: Consultancy. Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy. Kim: Novartis: Consultancy, Honoraria, Research Funding; Briston-Meyers Squibb: Consultancy, Honoraria, Research Funding; Paladin: Consultancy; Pfizer: Consultancy. Haines: Novartis: Employment. Bonifacio: Novartis: Employment. Rine: Novartis: Employment. Purkayastha: Novartis Pharmaceuticals Corporation: Employment.

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
naczx完成签到,获得积分0
9秒前
27秒前
冷傲半邪完成签到,获得积分10
27秒前
量子星尘发布了新的文献求助10
39秒前
1分钟前
1分钟前
1分钟前
紫熊发布了新的文献求助20
1分钟前
汉堡包应助栗先森采纳,获得10
1分钟前
1分钟前
栗先森发布了新的文献求助10
1分钟前
1分钟前
栗先森完成签到,获得积分10
1分钟前
隐形曼青应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
2分钟前
量子星尘发布了新的文献求助10
2分钟前
Dreamhappy完成签到,获得积分10
2分钟前
yindi1991完成签到 ,获得积分10
2分钟前
Krim完成签到 ,获得积分10
2分钟前
2分钟前
3分钟前
3分钟前
紫熊完成签到,获得积分10
3分钟前
量子星尘发布了新的文献求助10
3分钟前
CodeCraft应助科研通管家采纳,获得10
4分钟前
十月天秤完成签到,获得积分0
4分钟前
4分钟前
泥娃娃完成签到,获得积分10
4分钟前
natsu401完成签到 ,获得积分10
4分钟前
铜豌豆完成签到 ,获得积分10
4分钟前
ldjldj_2004完成签到 ,获得积分10
4分钟前
方白秋完成签到,获得积分10
5分钟前
青柠完成签到 ,获得积分10
5分钟前
5分钟前
5分钟前
量子星尘发布了新的文献求助10
5分钟前
lyj完成签到 ,获得积分10
5分钟前
叁月二完成签到 ,获得积分10
6分钟前
科研通AI2S应助科研通管家采纳,获得10
6分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
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 3976683
求助须知:如何正确求助?哪些是违规求助? 3520770
关于积分的说明 11204819
捐赠科研通 3257565
什么是DOI,文献DOI怎么找? 1798733
邀请新用户注册赠送积分活动 877897
科研通“疑难数据库(出版商)”最低求助积分说明 806629