ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone

来那度胺 克拉斯 医学 神经母细胞瘤RAS病毒癌基因同源物 肿瘤科 内科学 多发性骨髓瘤 癌症研究 癌症 结直肠癌
作者
Yasunori Kogure,Hiroshi Handa,Yuta Ito,Masaki Ri,Yuichi Horigome,Masaki Iino,Yoriko Harazaki,Takahiro Kobayashi,Masahiro Abe,Tadao Ishida,Shigeki Ito,Hiromi Iwasaki,Junya Kuroda,Yuzuru Kanakura,Kazutaka Sunami,Hiroyuki Takamatsu,Hideto Tamura,Toshiaki Hayashi,Kiwamu Akagi,Tomohiro Shinozaki,Takahiro Yoshida,Ikuo Mori,Shinsuke Iida,Takahiro Maeda,Keisuke Kataoka
出处
期刊:Blood [Elsevier BV]
被引量:4
标识
DOI:10.1182/blood.2023022540
摘要

It remains elusive how driver mutations, including those detected in circulating tumor DNA (ctDNA), affect prognosis in relapsed/refractory multiple myeloma (RRMM). Here we performed targeted-capture sequencing using bone marrow plasma cells (BMPC) and ctDNA of 261 RRMM cases uniformly treated with ixazomib, lenalidomide, and dexamethasone in a multicenter, prospective, observational study. We detected 24 and 47 recurrently mutated genes in BMPC and ctDNA, respectively. In addition to clonal hematopoiesis-associated mutations, varying proportion of driver mutations, particularly TP53 mutations (59.2% of mutated cases), were present in only ctDNA, suggesting their subclonal origin. In univariable analyses, ctDNA mutations of KRAS, TP53, DIS3, BRAF, NRAS, and ATM were associated with worse progression-free survival (PFS). BMPC mutations of TP53 and KRAS were associated with inferior PFS, while KRAS mutations were prognostically relevant only when detected in both BMPC and ctDNA. A total number of ctDNA mutations in the six relevant genes was a strong prognostic predictor (2-year PFS rates: 57.3%, 22.7%, and 0% for 0, 1, and ≥ 2 mutations, respectively) and independent of clinical factors and plasma DNA concentration. Using the number of ctDNA mutations, plasma DNA concentration, and clinical factors, we developed a prognostic index (ctRRMM-PI), classifying patients into three categories with 2-year PFS rates of 57.9%, 28.6%, and 0%. Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.
最长约 10秒,即可获得该文献文件

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
刚刚
量子星尘发布了新的文献求助10
刚刚
NARUTO完成签到 ,获得积分10
1秒前
斯文麦片发布了新的文献求助10
1秒前
2秒前
orange9发布了新的文献求助10
4秒前
4秒前
苜久久完成签到,获得积分10
6秒前
8秒前
9秒前
敏感的莆发布了新的文献求助10
9秒前
11秒前
华仔应助科研通管家采纳,获得10
11秒前
大模型应助科研通管家采纳,获得10
11秒前
Lucas应助科研通管家采纳,获得50
11秒前
Owen应助科研通管家采纳,获得10
11秒前
wanci应助科研通管家采纳,获得10
12秒前
搜集达人应助科研通管家采纳,获得10
12秒前
12秒前
12秒前
12秒前
12秒前
皮皮发布了新的文献求助150
12秒前
15秒前
16秒前
小乘号子完成签到,获得积分10
17秒前
18秒前
科研通AI5应助susan采纳,获得10
19秒前
脑洞疼应助miaolingcool采纳,获得10
19秒前
小飞侠完成签到,获得积分10
20秒前
爆米花应助guyuefanxing采纳,获得10
22秒前
淡然冬灵发布了新的文献求助10
22秒前
易千妤完成签到 ,获得积分10
23秒前
hhhblabla发布了新的文献求助10
24秒前
25秒前
28秒前
29秒前
30秒前
djbj2022给djbj2022的求助进行了留言
30秒前
南河完成签到 ,获得积分10
30秒前
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
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Comparison analysis of Apple face ID in iPad Pro 13” with first use of metasurfaces for diffraction vs. iPhone 16 Pro 500
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 4039382
求助须知:如何正确求助?哪些是违规求助? 3577178
关于积分的说明 11377000
捐赠科研通 3306701
什么是DOI,文献DOI怎么找? 1819582
邀请新用户注册赠送积分活动 892899
科研通“疑难数据库(出版商)”最低求助积分说明 815164