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

Abstract

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.

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Fig. 1: Day 0 alemtuzumab concentrations and pharmacokinetic modeling.

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Acknowledgements

This work was supported by a Cincinnati Children’s Research Foundation GAP award.

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DA, CE, TF, MD, AV, PM, and RM analyzed data and wrote the manuscript. CE, TF, and MD performed modeling and simulation work. PM and AV contributed expertise and supervision of modeling and simulation work. RM and KM coordinated clinical aspects of the study. AL supervised statistical analyses for the manuscript. LN and RM measured or supervised alemtuzumab levels, respectively. ACL and FA measured anti-alemtuzumab antibodies. ATC coordinated pharmacy aspects of the study. SC, MBJ, ASN, KCM, SMD, PAM, and RAM contributed patients. All authors reviewed and contributed to editing of the manuscript.

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Correspondence to Rebecca A. Marsh.

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Competing interests

SMD receives research funding from Alexion and is a consultant with Novartis Pharmaceuticals. KCM is a consultant with Novartis Pharmaceuticals. The remaining authors have no relevant conflicts of interest to disclose.

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Arnold, D.E., Emoto, C., Fukuda, T. et al. A prospective pilot study of a novel alemtuzumab target concentration intervention strategy. Bone Marrow Transplant 56, 3029–3031 (2021). https://doi.org/10.1038/s41409-021-01460-1

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