The FDA currently recommends at least 4 hours of recipient monitoring to detect early infusion reactions; recent catastrophic reactions to “first in man” biological agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious.
We therefore reviewed infusion-related adverse events (AEs) following administration of ex-vivo expanded T cell products (antigen specific CTLs, allodepleted T cells and genetically modified T cells) on Investigational New Drug (IND) studies in our center.
From 1998 to 2008, we infused 381 T cell products to 180 recipients, enrolled on 18 studies, receiving T cells targeting malignancies or post-transplant viral infections. There were no Grade 3-4 infusion reactions during initial monitoring or 24 hour follow-up. Twenty four mild (grade 1-2) adverse events (AEs) occurred in 21 infusions either during or immediately following infusion (up to 6 hours), most commonly nausea and vomiting (10/24; 41.6%), likely due to the DMSO cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. 22 additional non-severe events were reported within 24 hours of infusion, most commonly culture negative fever, chills and nausea. Increased risk of adverse effects was associated with age (IRR 0.98; 95% CI 0.96-1.00; p=0.05), while an increase risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72; 95% CI 1.00-7.40; p=0.05); sex, disease type or T cell source (allogeneic or autologous) had no effect on frequency of adverse events.
Hence infusion of T cells is safe in the outpatient setting and associated with no severe reactions, so that monitoring for one hour after infusion is likely sufficient. As many of the AEs were attributable to diphenhydramine premedication, a lower dose (0.25mg/kg) should be selected.
Keywords: T cells, Cytotoxic T Lymphocytes, Epstein-Barr virus, Infusion reaction, Adverse events