TY - JOUR
T1 - Adverse events following infusion of T cells for adoptive immunotherapy
T2 - A 10-year experience
AU - Cruz, Conrad Russell
AU - Hanley, Patrick J.
AU - Liu, Hao
AU - Torrano, Vicky
AU - Lin, Yu Feng
AU - Arce, James A.
AU - Gottschalk, Stephen
AU - Savoldo, Barbara
AU - Dotti, Gianpietro
AU - Louis, Chrystal U.
AU - Leen, Ann M.
AU - Gee, Adrian P.
AU - Rooney, Cliona M.
AU - Brenner, Malcolm K.
AU - Bollard, Catherine M.
AU - Heslop, Helen E.
N1 - Funding Information:
This work was supported by grants RO1CA061384, PO1 CA94237, P50CA126752 and U54HL081007 from the National Institutes of Health and a SCOR from the Leukemia and Lymphoma Society . We wish to thank all the clinicians involved in the care of the patients, the staff in the GMP facilities who manufactured the cells and all the research staff who collected data.
PY - 2010/10
Y1 - 2010/10
N2 - Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic 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. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. 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 34 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 12) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.961.00, P 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.007.40, P 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected.
AB - Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic 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. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. 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 34 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 12) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.961.00, P 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.007.40, P 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected.
KW - Adverse events
KW - Cytotoxic T lymphocytes
KW - EpsteinBarr virus
KW - Infusion reaction
KW - T cells
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U2 - 10.3109/14653241003709686
DO - 10.3109/14653241003709686
M3 - Article
C2 - 20429793
AN - SCOPUS:77957305203
SN - 1465-3249
VL - 12
SP - 743
EP - 749
JO - Cytotherapy
JF - Cytotherapy
IS - 6
ER -