Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma

IF 4.3 Q1 Medicine
Kathleen Monahan , Ariel Kleman , Bicky Thapa , Aniko Szabo , Anita D'Souza , Binod Dhakal , James H. Jerkins , Marcelo C. Pasquini , Mehdi Hamadani , Parameswaran N. Hari , Saurabh Chhabra
{"title":"Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma","authors":"Kathleen Monahan ,&nbsp;Ariel Kleman ,&nbsp;Bicky Thapa ,&nbsp;Aniko Szabo ,&nbsp;Anita D'Souza ,&nbsp;Binod Dhakal ,&nbsp;James H. Jerkins ,&nbsp;Marcelo C. Pasquini ,&nbsp;Mehdi Hamadani ,&nbsp;Parameswaran N. Hari ,&nbsp;Saurabh Chhabra","doi":"10.1016/j.bbmt.2020.08.030","DOIUrl":null,"url":null,"abstract":"<div><p>High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence. We compared the outcomes of consecutive patients with myeloma undergoing autoHCT using the 2 formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) to the newer one (PGF-Mel). Of 294 autoHCT recipients, 162 received PG-Mel conditioning and 132 received PGF-Mel conditioning. The PGF-Mel group was older and had a lower average Karnofsky Performance Status score. PGF-Mel was associated with faster neutrophil recovery (median, 12 days versus 13 days; <em>P</em> &lt; .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; <em>P</em> = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; <em>P</em> = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 12","pages":"Pages 2229-2236"},"PeriodicalIF":4.3000,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.030","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Blood and Marrow Transplantation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1083879120305747","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 2

Abstract

High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence. We compared the outcomes of consecutive patients with myeloma undergoing autoHCT using the 2 formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) to the newer one (PGF-Mel). Of 294 autoHCT recipients, 162 received PG-Mel conditioning and 132 received PGF-Mel conditioning. The PGF-Mel group was older and had a lower average Karnofsky Performance Status score. PGF-Mel was associated with faster neutrophil recovery (median, 12 days versus 13 days; P < .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; P = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; P = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.

无丙二醇Melphalan与PG-Melphalan对骨髓瘤自体造血细胞移植的调节作用。
自体造血细胞移植(autoHCT)前大剂量美法兰(Mel)调理是适合移植的多发性骨髓瘤患者的标准治疗方法。传统的冻干梅尔配方在重组后的溶解度和稳定性不足,导致使用丙二醇(PG)作为增溶剂。一种新的不含pg的Mel制剂(Evomela)使用-环糊精captisol作为增溶剂,并被美国食品和药物管理局批准作为调理剂,基于一项显示生物等效性的单相IIb研究。我们比较了连续接受自体hct的骨髓瘤患者使用两种配方的Mel进行调节的结果,我们的中心从使用旧配方(PG-Mel)切换到使用新配方(PGF-Mel)。在294例自体hct受体中,162例接受PG-Mel调节,132例接受PGF-Mel调节。PGF-Mel组年龄较大,平均Karnofsky表现状态评分较低。PGF-Mel与更快的中性粒细胞恢复相关(中位数,12天对13天;P & lt;.001), 30天内3-4级感染较少(1.5%对8.0%;P = 0.048), 30天再住院率较低(6.8%对17.9%;P = .04),倾向加权分析证实了这一点。在粘膜炎、器官毒性、骨髓瘤反应或100天死亡率方面,两组间无显著差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信