Alemtuzumab is a monoclonal antibody that targets cell surface antigen CD52 on lymphocytes. It has been used to treat hematologic malignancies and has been incorporated into hematopoietic stem cell transplant (HSCT) conditioning regimens. However, few studies have evaluated the pharmacology of alemtuzumab in adults with sickle cell disease (SCD).
This study, published in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, analyzed the pharmacokinetics and pharmacodynamics of alemtuzumab in adults with SCD who received HSCT. The study included 22 adults with SCD who received a matched related donor HSCT. The purpose of the study was to see if alemtuzumab clearance affects transplant outcomes.
Patients received one of two nonmyeloablative allogeneic HSCT regimens, including alemtuzumab and total body irradiation, or pentostatin, cyclophosphamide, alemtuzumab, and total body irradiation. Data on alemtuzumab serum concentrations, absolute lymphocyte counts, and T-cell (CD3) and myeloid chimerism (CD14/15) were gathered. A pharmacokinetics population model was used to help understand pharmacological variation.
Ultimately, it was found that alemtuzumab clearance correlated differently with certain parameters at different times following treatment. No correlation was found between alemtuzumab levels and CD14/15 chimerism. Lastly, at 2 to 4 months after transplant, higher alemtuzumab levels measured 14 days after transplant were associated with better engraftment. The researchers concluded that more lymphodepletion might be required to reduce graft failure on these two non-myeloablative matched related donor HSCT regimens .
Source: Furstenau, D., Peer, C. J., Hughes, T. E., Uchida, N., Tisdale, J., Hall, O. M., Figg, W. D., & Hsieh, M. (2021). Alemtuzumab clearance, lymphocyte count, and T‐cell chimerism after hematopoietic stem cell transplant in sickle cell disease. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. https://doi.org/10.1002/phar.2641