A prospective pilot study of a novel alemtuzumab target concentration intervention strategy

被引：7

作者：

Arnold, Danielle E. ^{[1
]}

Emoto, Chie ^{[2
]}

Fukuda, Tsuyoshi ^{[2
]}

Dong, Min ^{[2
]}

Vinks, Alexander A. ^{[2
]}

Lane, Adam ^{[1
]}

McIntosh, Kelly ^{[1
]}

Neumeier, Lisa ^{[1
]}

Lankester, Arjan C. ^{[3
]}

Achini, Federica ^{[4
]}

Teusink-Cross, Ashley ^{[2
]}

Chandra, Sharat ^{[1
]}

Jordan, Michael B. ^{[1
]}

Nelson, Adam S. ^{[1
]}

Myers, Kasiani C. ^{[1
]}

Davies, Stella M. ^{[1
]}

Mehta, Parinda A. ^{[1
]}

Marsh, Rebecca A. ^{[1
]}

机构：

[1] Univ Cincinnati, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati Childrens Hosp, Dept Pediat,Coll Med,Med Ctr, Cincinnati, OH 45267 USA

[2] Univ Cincinnati, Med Ctr, Coll Med, Dept Pediat,Div Pharmacol,Cincinnati Childrens Ho, Cincinnati, OH 45267 USA

[3] Leiden Univ, Dept Pediat, Div Stem Cell Transplantat, Med Ctr, Leiden, Netherlands

[4] Leiden Univ, Willem Alexander Childrens Hosp, Dept Pediat, Lab Pediat Immunol,Med Ctr, Leiden, Netherlands

来源：

BONE MARROW TRANSPLANTATION | 2021年 / 56卷 / 12期

关键词：

HEMATOPOIETIC-CELL TRANSPLANTATION; MIXED CHIMERISM; IN-VIVO; PHARMACOKINETICS; IMPACT; GVHD;

D O I：

10.1038/s41409-021-01460-1

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Alemtuzumab is used as part of reduced-intensity and reduced-toxicity transplant conditioning regimens for nonmalignant diseases. Prior studies identified an ideal target concentration range of 0.15-0.6 mcg/mL at day 0. However, only 24% of patients fall within this window using standard intermediate dosing. We performed a pilot study of a novel target concentration intervention strategy to target day 0 alemtuzumab concentrations to 0.15-0.6 mcg/mL. Twelve patients received model-informed alemtuzumab dosing of 0.5-0.6 mcg/kg divided over days -14 to -12. Alemtuzumab concentrations were measured, and pharmacokinetic (PK) modeling was performed on day -5 to predict day 0 concentrations. If the day 0 alemtuzumab concentration was predicted to fall below 0.15 mcg/mL, simulations were performed to identify the individual "top-up" dose needed to achieve the target day 0 concentration window. Six (50%) patients achieved day 0 alemtuzumab concentrations between 0.15 and 0.6 mcg/mL (4 received a top-up dose). Five patients had day 0 concentrations above the target window (no top-up doses). One patient had a day 0 concentration below the target range in the presence of anti-alemtuzumab antibodies. A concentration intervention strategy approach to alemtuzumab treatment can successfully target a greater proportion of patients into the ideal therapeutic window. Additional dose-reduction studies are needed to further optimize the initial dosing and achieve target attainment in all patients.

引用

页码：3029 / 3031

页数：3

共 9 条

[1] Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution [J].